- Email: [email protected]
Study of Pd-elimination under carbonylation conditions: Regioselective formation of esters
TETRAHEDRON Tetrahedron 54 (1998) 1385 I-13866
Pergamon
Study of Pd-elimination under carbonylation conditions: Regioselective formation of esters Ana C. Albdniz, Pablo Espinet*~ and Yong-Shou Lin Depal*amento de Quimica Inorgdnica. Facultad de Ciencias. Universidad de Valladolid. 47005 Valladolid. Spain.
Received 21 May 1998; revised 3 September 1998; accepted 10 September 1998
Abstract The regioselective synthesis of methyl esters is achieved by carbonylation of two different types of organometallic derivatives resulting from insertion of non-conjugated dienes into a Pd-aryl bond. When the diene and the Pd-aryl synthon [PdPfBr(NCMe)2] (Pf = C6F5) are mixed at low temperature, solutions of 111_112_ enylpalladium complexes can be isolated and converted into ~3-aryl methyl esters by reaction with CO in the presence of methanolic solutions of sodium methoxide. When the reactions are carried out at room temperature q3-allylpalladitm~ complexes are isolated, and their carbonylation gives 13,y-unsaturated esters. © 1998 Elsevier Science Ltd. All rights reserved. Keywords: Palladium and compounds; carbonylation;regiocontrol
Introduction Palladium complexes provide excellent selectivity in the functionalization of dienes [ 1-7]. Nucleophilic attack to the diolefin (trans addition of Pd and the nucleophile), or insertion of one double bond into a Pd-R bond (cis addition) gives organometallic intermediates, usually rl3-allylpalladium complexes, that can be transformed into useful organic compounds (Scheme 1) [7]. The latter process can be referred to as a Pd-elimination process incorporating an X group in place of the palladium atom. The whole process can be carried out catalytically producing functionalized alkenes.
I
e-mail: [email protected]
0040-4020/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved. PII: S0040..4020(98)00852-7
13852
A. C. Albdniz et al. /Tetrahedron 54 (1998) 13851-13866
y-
/
x
Pd
.
\
Pd-Y Scheme 1
When the diolefin is a non-conjugated one, a number of Pd-H eliminations and readditions must occur (palladium migration) before the formation of the corresponding q3_ allyl derivative. Previous works show that, in appropriate systems and conditions, this palladium migration can take periods within the range of time used in the manipulation of an organic synthesis [8-10], and rl l-q2-enylpalladium complexes (A, Scheme 2) can be observed at low temperature as intermediates in the formation of the more stable rl3-allyl derivatives (B, Scheme 2). It should be possible to produce organic products derived either from A or from B (Scheme 2), provided that the Pd-elimination reaction chosen does not induce a fast Pd-migration. To test the feasibility of this idea a fast and efficient, as well as selective Pdelimination procedure was chosen: The substitution of palladium for an ester group.
--Pd-R
,
.
x
A
X
Pd-migration
/
Pd
\
X
~
R
Scheme 2
Carbonylation reactions assisted by transition-metal complexes have become an efficient method for the direct introduction of a carbonyl functional group into an organic molecule [5,11]. The reaction is stereoselective and occurs with retention of configuration at the former Pd-bound carbon [12-15]. The synthesis of carbonyl compounds from rl3-allylpalladium complexes has been carried out both as a stoichiometric reaction [12,13,16-19] or in a catalytic process involving rl3-allylpalladium intermediates [20-25]. There have also been a number of reports on the carbonylation of 111-rl2-enylpalladium complexes [ 14,26,27]. We
A. C. AIb(niz et al. / Tetrahedron 54 (1998) 13851-13866
13853
report here the use of the carbonylation reaction in a regio-controlled synthesis of esters from either rl l-rl2-enyl or rl3-allylpalladium complexes.
Results and Discussion
The carbonylation of the organometallic palladium derivatives was carried out by bubbling carbon monoxide through a solution of the palladium complex and sodium methoxide in CHC13/MeOH. The rl3-allylpalladium derivatives employed were prepared by reaction of [PdPfBr(NCMe)2] (Pf = C6F5) and the suitable diene at room temperature [810,28]. They are collected in Table 1, along with their corresponding organic esters. The rl 1_ q2-enyl complexes 17, 18, 19 and 20, intermediates in the formation of 1, 2, 6, and 7 from non-conjugated dienes, can be prepared in solution at low temperature, and are collected in Table 2 as well as their carbonylation products. Table 1. Carbon vlation of (q3-allvl)palladium complexes a Entry Diene b Complex
Pd 2
~
~
Product
Yield(%) c
~ P f
(5)
~ P f COOMe Me,,.~ MeOOC~R
(9)
COOMe P
f
(2)
Pd Pd
Me
95 96
H P f
Me (101)°
83
(111)cl
88
Pf--@COOMe
(121)d
92
~PIC2Hd"~
(13a)
48
Pf PI.--~ I
I
COOMe
PICH2/
MeOOC 48
PfC2Hd.-~ C O O M o (13b)
800
PfCH~'~
COOMo cH2Pf
(15)
a) Pf = C6F5; reaction conditions: (q3-allyl)palladium complex (0. I mmol) and NaOMe (0.6 mmol) in CHCI3/MeOH solution ( I:1 ) was saturated with CO (I atm) and reacted for 20 min at room temperature; b) Dienes used in the preparation of the (q3_ allyl)palladium complexes (see ref. 8-10, 28); c) determined by integration of 19F NMR signals; the remaining 4-5% in entries I, 2, 6 and 7 corresponds to a small amount of esters which could not be identified due to overlap of their I H NMR signals; d) mixed with unreacted starting q3-allyl complex: 17% for entry 3, 12% for entry 4, 8% for entry 5 and 12% for entry 7; e) isolated yield for 14 is 58%.
A. C. A lbt;niz et al. / Tetrahedron 54 (1998) 1385 I - 13866
13854
The major product in the carbonylation of the rl3-allylpalladium complexes in the presence of base (NaOMe) is a [3,),-unsaturated monoester. High regioselectivity is observed and insertion of CO occurs,at the less substituted allylic carbon (entries 1 and 2, Table 1) or the less hindered position (entries 3, 5 and 7, Table 1). The same selectivity has been reported before for the carbonylation of q3-allylpalladitml derivatives, both under mild conditions [13,16] or under high-pressure [17-19,23-25]. In every case, about 4% of unidentified ester compounds were detected which might correspond to carbonylation at the most substituted terminal allylic carbon. The formation of two isomeric esters in an approximate ratio 1:1 derived from 6 (entry 6, Table 1) reflects their close substitution pattern. The influence of the bulky C6F5 group, three carbons away from the allylic moiety, is negligible in this case but important in complex 5, where pentafluorophenyl is only one carbon apart and selective carbonylation occurs. The opposite regioselectivity (CO incorporation into the more substituted carbon) was found in the carbonylation of a complex analogous to 5 but showing trans Pd-OMe stereochemistry, di-g-chlorobis[(4-methoxy-l-3-q3-cyclohexenyl)dipalladium(lI), to trans-3-((diethylamino)carbonyl)-4-methoxy-l-cyclohexene in the presence of diethylamine [12]. In this case insertion of CO into the Pd-C seems to be favored when the methoxy group is in a [3-position. A Pd-H elimination product, 15 (4%), was formed in the carbonylation of 7. It could be formed by [3-H elimination in an q l-allyl intermediate with C-1 bound to palladium. The endo sterochemistry of the attack of the pentafluorophenyl group to a cyclic diene double bond has been confirmed by X-ray structure determinations of the palladium complexes formed [28,29]. Thus, the cyclic rl3-allylpalladium derivatives 4 and 5 show cis Pd-Pf
stereochemistry.
Compounds
6 and 7 are expected to be t r a n s due to the
stereochemistry of Pd-migration (cis-elimination-readditions). On the other hand, the carbonylation reaction is known to proceed with retention of configuration, and accordingly only one diastereoisomer (cis) was found in the esters derived from 4 and 5 (111 and 121, respectively). A trans arrangement is expected and proposed for the cyclohexene esters 13a, 13b and 14 (the latter as a mixture of the two diastereoisomers found in the starting material) [9], but their configuration could not be confirmed unequivocally because the high complexity of their IH NMR spectra prevented the measurement of vicinal coupling constants. The q3-allylpalladium complex 3, formed by insertion of trans,trans-2,4-hexadiene into the Pd-Pf bond, is obtained as a single diastereoisomer [28], and only one ester was obtained from it as a single diastereoisomer (101). Some unreacted q3-allylpalladium complex accompanied the final organic esters in some of these reactions (see entries 3-5, 7, Table 1). Addition of a larger amount of base (molar ratio: rl3-allyl/NaOMe = 1/12, instead of the usual 1/6) brought about the complete
A. C. AIb&d2. et al. / Tetrahedrm, 54 (1998) 13851-13866
13855
carbonylation of the starting materials, but lead to the epimerization of the final esters. Thus, the diastereoisomers 102 (25%), 112 (trans, 15%) and 122 (trans, 38%) were obtained.: The racemization of unsaturated esters in the presence of base by cz-deprotonation is a known process and the new diastereoisomers could result from the isomerization of the cis derivatives 111 and 121, or 101 [14,30]. This was confirmed when epimerization of ester 121 was actually observed upon addition of sodium methoxide. The formation of 102 might also be interpreted as a result of svn-anti isomerization of the methyl substituted allylic carbon in the starting palladium derivative 3: Carbonylation of 1-anti-2-svn-3 would give 102. However, svn-anti isomerization has not been observed in other carbonylation experiments or in the same experiment with less base; this leaves the base-promoted epimerization as the most likely cause of the formation of 102 [14].
MeOOC Me~ ~
H P
H
102
f
{~
OMe COOMe
Me pf
Pf
112
122
Pf = C6F5
The r I l-rl2-enyls 17, 18, 19 and 20 were prepared in situ by reaction of 1,5-hexadiene, 1,6-heptadiene, 4-vinyl-l-cyclohexene and R-(+)-limonene with [PdPfBr(NCMe)2] at low temperature in CH~CI'~ (see Table 2) [8-10]. 17 can also be isolated as a white solid by crystallization from Et20 when the arylation reaction is carried out at 0 °C for 5 min [10]. The relative rates of the insertion reaction of the diene into the Pd-Pf bond, coordination of the unattacked double bond to give the rl l-q2-enyl, and Pd-migration to form the final allyl derivatives, prevented the "in situ" preparation of pure solutions of the rl l-rl2-enyl complexes [8]. Some starting [PdPfBr(NCMe)2] complex and allyl derivatives were also present and, when the carbonylation reaction was carried out, the corresponding ester derivatives were obtained, which could be easily identified by NMR (Table 2). cx-Alkenyl pentafluorophenylpropanoic methyl esters were obtained in high yield in the carbonylation reactions of the linear q l-rl2-enylpalladium derivatives 17 and 18 (entries 1 and 2, Table 2). The same type of ester (23) was obtained as a major compound in the carbonylation of complex 19, although mixed with the esters derived from the corresponding allyl derivative and a Pd-H elimination product, 24 (entry 3, Table 2). Compound 23 is a 1:1 mixture of diastereoisomers, reflecting the ratio found for the starting complex 19.
2 A Pd-H elimination product E,E-2-(pentafluorophenyl)-2,4-hexadiene (16) which comprises 5% of the mixture is also observed in tile carbonylation reaction of 3 with excess base (3:NaOMe = 1:12), along with the diasteroisomers 101 (70%) and 102 (25%).
A. C. Alb~niz et al. / Tetrahedron 54 (1998) 1 3 8 5 1 - 1 3 8 6 6
13856
5
o
,,z,
E o
o
d
n
I
g
:
"6
© 0
o..
m
G
t'N
~0
Lt.
-
~
i e-
I
~
.-~
&
E
~ ¢"~. -4-
c "-
.:
g
~
"_~
p_
o
._o
2
~4
L Z ~ " l "; ±
E 0
tl'3
o
o
t'N
cq
~R
v
'5
15
i - o ~
S-~_
I=
.-=~.=_
.o
o z Z
~
~u_~
~
~- e,.I
t-..i
Io ~.o_=o I-=
,,_, = e-
~--~
~=g,-....
=
=
o~
•
e-
I
+
E r-,
4
i..
~..,:. ~
u
g,
e.i ¢-
.i.1
~
o ~.---~
._.-.-...~
A. C. AlbEniz et al. / Tetrahedron 54 (1998) 13851-13866
13857
The carbonylation reaction of the diastereomeric mixture of rll-rl2-enylpalladium complexes derived from limonene (201,202) at 253 K (entry 4, Table 2) [9] produced, by [5H elimination, the diene 26 as the major compound. In addition, two other [5-H elimination compounds (27, 28) were detected as minor products. Only small percentages of the methyl esters 251 and 252 were formed. Thus, this compound is reluctant to insertion of CO into the Pd-carbon bond, as found for other Pd-bound tertiary carbons, which do not undergo CO insertion [31]. The presence of carbon monoxide only promotes the [5-H elimination and the decoordination of the dienes formed in this way. [5,3,-unsaturated esters arising from the small amount of rl3-allyl derivatives present in the starting solutions (see above) were detected in each reaction (except for complexes 71 and 72 which do not react under the carbonylation conditions used in entry 4, Table 2). When some [PdPtBr(NCMe)2] is also present it gives methyl pentafluorobenzoate (30), and/or methyl 2,3,5,6-tetrafluoro-4-methoxy benzoate (31), resulting from nucleophilic substitution by methoxide of the activated Fpara in the aromatic ring on compound 30. The starting ratios r 1l-rl2-enyl:rl3-allyl are roughly maintained in their corresponding carbonylation products for every enyl derivative (Table 2), showing that Pd-migration is not promoted under the carbonylation conditions. When CO insertion is not a facile process, such as observed for complexes 20, [5-H elimination occurs followed by displacement of the newly formed dienes. The isomerization of the r I i-q2-enylpalladium complexes formed from R-(+)-limonene to the corresponding q3-allyl derivatives is diastereoselective: Complexes 201 and 202 isomerize with different activation energies and, by controlling the temperature, it is possible to have a solution mixture with 202 and the allyl derivative 71 as major products (the configuration of both diastereoisomers has been assigned on the basis of steric arguments, but could not be determined unequivocally) [9]. Carbonylation of a mixture of 201,202, 71 and 72 in the ratio shown in Scheme 3, obtained by reaction of R - ( + ) - l i m o n e n e and [PdPfBr(NCMe)2] at 273 K for 80 rain, gave the ester derivatives: 141, 142 and 25 (mixture of two diastereoisomers 251 and 252) in a 4:1:1 ratio. Since CO insertion into the Pd-tertiary carbon bonds of the 11l-q2-enylpalladium derivatives 201 and 202 is disfavored, the rest of the products obtained were [3-H elimination compounds (26, 2-methyl-5-[l'-methyl-l'(pentafluorophenylmethyl)]-methyl-l,3-cyclohexadiene (29) and a small amount of 27 and 28). They could be easily separated from the methyl esters by column chromatography. Thus, ester 141 is obtained as a single enantiomer with three asymmetric centers in 67% diastereomeric excess.
13858
A, C. Alb#niz et al. /Tetrahedron 54 (1998) 13851-13866
[PdPfBr(NCMe)2] Pf = C6F5 273 K 80 min 5
5
H CH3'"" 1 PfCH 2
r
I
l
PfCH2'""J
2"
2oi (14%)
I 2'
292 (42°1o)
H~ - -
+ PfCH 2
I
CH 3
PcI://~Y "\
H
71 (32'=/0)
72 (7%) 273 K CO NaOMelMeOH
~ ~
H2Pf
~
Me
CH2Pf
COOMe
COOMe
141 (2o°/o)
+
26 (40%)
e
+
+
_••H2Pf
Me COOMe
142 (4%)
+
27 (2'/o)
+
28 (4%)
2,5 (5%) +
~ H 2 P f
29 (130) Scheme 3
Conclusions The formation of intermediate r II-q2-enylpalladium complexes at low temperature, which arrest the Pd-migration process to form the thermodynamically more stable q3-allyl derivatives, can be advantageously used in the regioselective functionalization of the organic moiety. Thus, carbonylation reactions carried out on either type of derivative afford two
A. C. A lb~niz et al. / Tetrahedron 54 (1998) 13851-13866
13859
types of regioisomeric unsaturated methyl esters. This selection is possible because CO reacts fast and does not promote Pd-migration, thus the rl3-allyl complex is not formed from the rl 1_ rl2-enylpalladium derivative during the carbonylation process.
Experimental Section General Considerations. The yellow complexes 1 [8,10], 2 [8], 3 [28], 4 [28], 5 [28], 6 [9], 7 [9], 17 [8,10], and pale yellow solutions containing the r II-rl2-enylpalladium complexes 18 [8], 19 [9], and 20 [9],were prepared as reported in the literature. The diolefins employed were purchased from Aldrich, Lancaster or Janssen and used without further purification. IH and 19F NMR spectra were obtained on Bruker AC-300 and ARX-300 spectrometers at 293 K unless otherwise noted. Proton and carbon chemical shifts were referenced to TMS and 19F chemical shifts to CFCI3. Double irradiation and proton homonuclear correlation experiments were carried when necessary. IR spectra (Nujol mulls) were recorded on a Perkin-Elmer 883 spectrometer. Organic products were analyzed using an HP-5890 gas chromatograph connected to an HP-5988 mass spectrometer at an ionizing voltage of 70 eV and a quadrupole analyzer. Evaporation of solvents was carried out using a water pump to avoid evaporation of low boiling point organic derivatives of interest. Relative percentages of compounds formed are calculated according to the integration of 19F NMR signals; an error of _+ 0.5 % is assumed due to proximity of the resonances or spectral noise in the case of products with low abundance.
Carbonylation of the rl3-allylpalladium complexes. Carbonylation of 1. To a solution of the yellow complex 1 (0.052 g, 0.06 mmol) in CHC13 (10 mL) was added NaOMe (0.019 g, 0.36 retool) in anhydrous methanol (10 mL) at room temperature. CO was immediately bubbled through the mixture for 20 rain and palladium precipitated. The palladium metal was filtered and the filtrate was evaporated to dryness using a water pump. The residue was triturated with diethyl ether and filtered. Evaporation of the solvent gave a colorless oily residue, 8 (yield: 95%, determined by 19F NMR). The same procedure was employed for the carbonylation of complexes 2, 3, 4, 5, 6 and 7. The esters were obtained as colorless oily residues in every case and the yields are collected in Table 1. Additional purification procedures were used in some cases and they are described below. Carbonylation of complexes 3, 4, and 5 using double amount of NaOMe (0.038 g, 0.72 mmol) was carried out in the same way (see Results and Discussion). Diastereoisomers were not separated and they were characterized as a mixture in each case.
13860
A. C. A Ib~niz et al. / Tetrahedron 54 (1998) 13851-13866
8: 19F NMR (282 MHz, 5, CDCI3): -163.5 (m, Fmeta), -158.5 (t, Fpara), -144.8 (m, Fortho); IH NMR (300 MHz, 8, CDCI3): 5.56 (m, 2H, H 3, H4), 3.68 (s, 3H, COOMe), 3.04 (d, J = 4.9 Hz, 2H, H2), 2.68 (tt, J = 7.6, 4JH.F = 1.4 Hz, 2H, HT), 2.08 (m, 2H, H5), 1.66 (qui, J = 7.5 Hz, 2I-1, H6). IR (C=O): v = 1753 cm -1. MS (El): m/z(relative intensity): 308 (M+,6), 276 (37), 194 (16), 181 (67), 68 (35), 67 (28), 59 (100), 53 (20), 41 (14). HRMS calcd for CI4HI3F502, m/z 308.0836; found 308.0835. 9: 19F NMR (282 MHz, 5, CDCI3): -163.5 (m, Fmeta), -158.7 (t, Fpara), -144.9 (m, Fortho); 1H NMR (300 MHz, 8, CDCI3): 5.52 (m, J = 5.8, 1.0 Hz, 2H, H 3, H4), 3.68 (s, 3H, COOMe), 3.03. (dd, J = 5.8, 1.0 Hz, 2H, H2), 2.68 (tt, J = 7.5, 4JH-F = 1.6 Hz, 2H, HS), 2.06 (m, J = 7.3 Hz, 2H, H5), 1.57 (qui, J = 7.3 Hz, 2H, HT), 1.42 (qui, J = 7.3 Hz, 2H, H6). IR (C=O): v = 1752 cm -1. MS (El): m/z(relative intensity): 322 (M+,2), 194 (20), 181 (100), 141 (14), 119 (14), 109 (17), 96 (15), 81 (33), 74 (43), 67 (19), 58 (35), 41 (14). HRMS calcd for C I5HIsFsO2, m/z 322.0992; found 322.1004. 101: 19F NMR (282 MHz, 8, CDC13): -163.0 (m, Fmeta), -158.11 (t, Fpara), -143.3 (m, Fortho); IH NMR (300 MHz, 5, CDCI3): 5.77 (dd, J = 15.3, 6.9 Hz, IH, H3), 5.65 (dd, J = 15.3, 7.5 Hz, 1H, H4), 3.89 (m, J = 7.2, 6.9 Hz, 1H, H2), 3.67 (s, 3H, COOMe), 3.12 (m, J = 7.5, 7.1 Hz, 1H, H5), 1.41 (d, J = 7.2 Hz. 3H, Me), 1.25 (d, J = 7.1 Hz, 3H, H6). IR (C=O): v = 1751 cm -1. MS (El): m/z(relative intensity): 308 (M +, 24), 249 (51), 248 (40), 233 (36), 221 (39), 207 (58), 195 (28), 187 (25), 181 (100), 88 (71), 59 (46), 55 (20). HRMS calcd for C14H13F502, m/z 308.0836; found 308.0845. 102: 19F NMR (282 MHz, 5, CDC13): -163.0 (m, Fmeta), -158.09 (t, Fpara), -143.3 (m, Fortho); IH NMR (300 MHz, 5, CDC13): 5.77 (dd, J = 15.3, 6.9 Hz, 1H, H3) *, 5.65 (dd, J = 15.3, 7.5 Hz, IH, H4) *, 3.89 (m, J = 7.2, 6.9 Hz, 1H, H2) *, 3.68 (s, 3H, COOMe), 3.12 (m, J 7.1 Hz, 1H, HS) *, 1.41 (d, J = 7.2 Hz, 3H, Me)*, 1.23 (d, J = 7.1 Hz, 3H, H6). IR
= 7.5,
(C=O): v = 1751 cm-l. *: overlapped with signals of 101 111: 19F NMR (282 MHz, 5, CDCI3): -162.8 (m, Fmeta), -157.6 (t, Fpara), -143.2 (m, Fortho); IH NMR (300 MHz, 8, CDCI3): 5.85-5.9 (m, 2H, H 2, H3), 3.71 (s, 3H, COOMe), 3.34 (m, 2H, H l, H5), 2.1-2.5 (m, 4H, H 4, H6). IR (C=O): v = 1750 cm -1. MS (El): m/z(relative intensity): 306 (M +, 17), 274 (16), 247 (63), 246 (62), 194 (17), 181 (96), 66 (16), 59 (100), 51 (11). HRMS calcd for CI4HI IF502, m/z 306.0679; found 306.0692. 112: 19F NMR (282 MHz, 5, CDCI3): -163.0 (m, Fmeta), -157.9 (t, Fpara), -143.1 (m, Fortho); I H NMR (300 MHz, 5, CDC13): 5.8-5.9 (m, 2H, H 2, H3) *, 3.73 (s, 3H, COOMe), 3.34 (m, 2H, H l, HS) *, 2.1-2.5 (m, 4H, H4, H6) *. IR (C=O): v = 1750 cm -1. *: overlapped with signals of 111. 121: 19F NMR (282 MHz, 5, CDCI3): -163.0 (m, Fmeta), -157.7 (t, Fpara), -143.1 (m, Fortho); IH NMR (300 MHz, ~5, CDCI3): 5.98 (m, J = 10.0, 4.8, 2.8 Hz, 1H, H2), 5.74 (m, J = 10.0,
A. C. A lb~niz et al. / Tetrahedron 54 (I 998) 13851-13866
13861
2.2, 0.9 Hz, IH, H3), 3.8 (m, J = 2.8, 2.2 Hz, 1H, HI), 3.72 (s, 3H, COOMe), 3.16 (m, J = 4.8, 0.9 Hz, IH, H4), 2.29 (m, 1H, H5), 1.90 (m, 2H, H6), 1.81 (m, 1H, HS'). IR (C=O): v = 1746 cm -1. MS tEl): m/z(relative intensity): 306 (M +, 9), 247 (39), 246 (90), 181 (100), 169 (10), 79 (197, 77 (36), 66 (12), 59 (92), 53 (16), 51 (187. HRMS calcd for CI4HIIF502, m/z 306.0679; found 306.0673. 122: 19F NMR (282 MHz, 8, CDC13): -162.9 (m, Fmeta), -157.6 (t, Fpara), -143.5 (m, Fortho); IH NMR (300 MHz, 8, CDCI3): 5.98 (m, 1H, H2), 5.74 (m, 1H, H3) *, 3.8 (m, 1H, HI) *, 3.72 (s, 3H, COOMe)*, 3.27 (m, IH, H4), 2.2 (m, IH, H5), 2.05 (m, 1H, H6), 1.75-2.0 (m, 2H, H 6', H5'). IR (C=O): v = 1746 cm -1. • : overlapped with signals of 121. 13a: 19F NMR (282 MHz, 5, CDCI3): -163.3 (m, Fmeta), -158.4 (t, Fpara), -145.1 (m, Fortho); tH NMR (300 MHz, ~5, CDCI3): 5.86 (m, 1H, H3), 5.59 (m, H, H2), 3.69 (s, 3H, COOMe), 2.89 (m, 1H, HI), 2.74 (t, J = 7.4 Hz, 2H, PfCH2)*, 1.9-2.15 (m, 4H, H 4, H 5, H6) *, 1.45-1.7 (m, 2H, PfCH2CH2)*, 1.38 tin, IH, H5'). IR (C=O): v = 1750 cm -1. MS** tEl): m/z(relative intensity): 334 (M +, 32), 275 (48), 274 (66), 181 (1007, 93 (82), 81 (38), 79 (67), 77 (37), 67 (29), 41 (9). HRMS calcd for CI6HI5F502, m/z 334.0992; found 334.1002. • : overlapped with signals of 13b. 13b: 19F NMR (282 MHz, 8, CDC13): -163.3 (m, Fmeta), -158.4 (t, Fpara), -145.0 (m, Fortho); IH NMR (300 MHz, 5, CDCI3): 5.7-5.85 (m, 2H, H 2, H3), 3.70 (s, 3H, COOMe), 3.11 (m, IH, HI), 2.74 (t, J = 7.4 Hz, 2H, PfCH2)*, 1.9-2.15 (m, 3H, H 4, H 5, H6) *, 1.76 (m, 1H, H6'), 1.45-1.7 (m, 2H, PfCH2CH2)*, 1.30 (m, IH, HS'). IR (C=O): v = 1750 cm -1. MS** (El): m/z(relative intensity): 334 (M +, 2), 275 (21), 274 (38), 181 (42), 93 (100), 79 (38), 77 (22), 41 (4). HRMS calcd for Ct6HI5FsO2, m/z 334.0992; found 334.1002. • : overlapped with signals of 13a • *: MS spectra for 13a and 13b could be reversed since it was not possible to distinguish them. Preparative TLC (silica gel) with n-hexane/EtOAc (9:1) as eluent was used for the separation of the diastereomeric mixture of esters 14 (Rf = 0.6, isolated yield: 58%) from unreacted Pd complex which is soluble in diethyl ether. 141: 19F NMR (282 MHz, 5,-CDC13): -163.4 (m, Fmem), -158.2 (t, Fpara), -143.7 (m, Fortho); IH NMR (300 MHz, 5, CDC13): 5.29 (b, IH, H2), 3.72 (s, 3H, COOMe), 3.17 (m, J = 8.5 Hz, IH, HI), 2.75 (db, J = 13.3 Hz, 1H, PfCHH'), 2.39 (dd, J = 13.3, 11.7 Hz, IH, PfCHH'), 1.95-2.1 (m, J = 8.5 Hz, 3H, H 4, H6), 1.73-1.9 (m, 2H, H5, PfCH2CH(Me)-), 1.70 (sb, 3H, Me3), 1.45 (m, 1H, H5'), 0.86 (d, J = 6.8 Hz, 3H, PfCH2CH(Me)-). IR (C=O): v = 1748 cm -1. MS (El): m/z(relative intensity): 362 (M +, 3), 181 (76), 121 (65), 93 (88), 91 (54), 81 (100), 79 (74), 77 (64), 59 (63), 41 (30). HRMS calcd for CI8HI9F502, m/z 362.1305, found 362.1303.
13862
A. C. Alb6niz et al. / Tetrahedron 54 (1998) 13851-13866
142: 19F NMR (282 MHz, 8, CDCI3): -163.3 (m, Fmeta), -158.0 it, Fpara), -144.0 (m, Fortho); IH NMR (300 MHz, 8, CDC13): 5.24 (b, 1H, H2), 3.62 (s, 3H, COOMe), 3.05 (m, J = 8.5 Hz, IH, HI), 2.73 (dd, J = 15.{), 9.2 Hz, IH, PfCHH'), 2.61 (dd, J = t5,0, 5.8 Hz, IH, PfCHH'), 1.95-2.1 (m, 2H, H4) *, 1.73-1.9 (m, J = 8.5 Hz, 3H, H6, H 5, PfCH2CH(Me)-)*, 1.67 (s, 3H, Me3), 1.33 (m, IH, H5'), 0.86 (d, J = 6.8 Hz, 3H, PfCH2CH(Me)-)*. IR (C=O): v = 1748 cm1. MS (El): m/z(relative intensity): 362 (M +, 3), 181 (46), 121 (55), 93 (81), 91 (46), 81 (100), 79 (65), 77 (60), 59 (47), 41 (32). HRMS calcd for CISHI9F502, rrdz 362.1305, found 362.1303. *: overlapped with signals of 141.
15: Colorless oil. It can be separated by silica gel colunm chromatography eluting with nhexane. 19F NMR (282 MHz, 8, CDC13): -163.4 (m, Fmeta), -158.2 (dr, Fpara)*, -143.6 (m, Fortho); 1H NMR (300 MHz, 8, CDCI3): 6.23 (m, J = 10. I Hz, 1H, H2), 5,65-5.8 (m, J = 10.1 Hz, 1H, H3), 4.80 (b, 2H, CH2=), 2.76 (m, IH, PfCHH'), 2.45-2.6 (m, 3H, H4, H 6, PfCHH'), 2.3 (m, IH, H6'), 1.87 (m, J = 6.8 Hz, IH, PfCH2CH(Me)-), 1.5-1.6 (m, 2H, H5), 0.87/0.85 (d, J = 6.8 Hz, 3H, Me)*. MS (El): m/z(relative intensity): 302 (M+, 4), 181 (20), 121 (31), 93 (100), 91 (70), 79 (34), 77 (75), 65 (29), 53 (22), 51 (21), 41 (32). HRMS calcd for C|6HI5F5, m/z 302.1094; found 302.1087. *: two signals corresponding to the mixture of two diastereoisomers. 16: Colorless oil. It was separated by column chromatography (silica gel) using n-hexane as eluent. 19F NMR (282 MHz, 8, CDC13): -163.3 (m, Fmeta), -157.9 (t, Fpara), -142.6 (m, Fo,.tho); 1H NMR (300 MHz, 8, CDC13): 6.40 (m, J = 15.0, 10.8 Hz, 1H, H4), 6.11 (d, J = 10.8 Hz, 1H, H3), 5.85 (m, J = 15.0, 6.9 Hz, 1H, H5), 2.05 (s, 3H, HI), 1.85 (d, J = 6.9 Hz, 3H, H6). MS (El): m/z(relative intensity): 248 (M +, 47), 233 (100), 218 (12), 213 (17), 187 (13), 183 (19), 181 (39), 169 (12), 143 (10), 51 (8).
Carbonylation of the ql-q2-enylpalladium complexes. Carbonylation of 18. [Pd(C6F5)Br(NCMe)2] (0.050 g, 0.115 retool) in CH2CI2 (10 mL) was cooled to -30 °C, and 1,6-heptadiene (0.0155 mL, 0.115 retool) was added. The mixture was kept at that temperature for 50 rain. After this time a pale yellow solution containing 18 (91%), the allyl derivative 2 (3%) and [Pd(C6F5)Br(NCMe)2] (6%) was obtained as shown by 19F NMR. A solution of NaOMe (0.037 g, 0.690 retool) in anhydrous MeOH (10 mL) at -30 °C was added to the mixture. Carbon monoxide was immediately bubbled through the solution for 20 min at that temperature. After warming to room temperature and filtering off the palladium metal, the solution was evaporated and residue was triturated with Et20. The suspension was filtered and the filtrate was evaporated to dryness; a colorless oily residue was obtained (24 mg), which was a mixture of 22 (86%), 9 (5%), C6Fs-COOMe (30, 5%) and unidentified esters (4%).
A. C. Albc;niz et al. / Tetrahedron 54 (1998) 13851-13866
13863
22: 19F NMR (282 MHz, 8, CDCI3): -162.9 (m, Fmeul), -156.9 (t, Fpara), -143.3 (m, Fortho); IH NMR (300 MHz, 5, CDC13): 5.75 (m, IH, H6), 4.96 (m, 2H, H7), 3.65 (s, 3H, COOMe), 3.01 (dd, J = 14.0, 8.6 Hz, IH, PfCHH'), 2.85 (dd, J = 14.0, 6.3 Hz, IH, PfCHH3, 2.68 (m, J = 8.6, 6.3 Hz, 1H, H2), 2.05 (q, J = 7.3 Hz, 2H, HS), 1.69 (m, 1H, H4), 1.51 (m, 1H, H4'), 1.42 (m, 2H, H3). IR (C=O): v = 1750 cm -1. MS (El): m/z(relative intensity): 322 (M +, 13), 254 (57), 221 (19), 194 (79), 181 (100), 141 (27), 81 (17), 69 (19), 59 (17), 55 (16), 41 (18). HRMS calcd for CI5HI5F502, m/z 322.0992; found 322.0997. Table 2 lists the conditions used to generate solutions containing 17, 19 or 20 and their composition. Carbonylation reactions were carried out on these solutions as indicated above for complex 18 to obtain colorless oily residues that contained the products collected in Table 2. Mixtures of products were not separated except when noted. 21: 19F NMR (282 MHz, 8, CDC13): -163.0 (m, Fmeta), -156.9 (t, Fpara), -143.3 (m, Fortho); IH NMR (300 MHz, 8, CDC13): 5.73 (m, IH, H5), 4.99 (m, 2H, H6), 3.64 (s, 3H, COOMe), 3.01 (dd, J = 13.9, 8.5 Hz, IH, PfCHH'), 2.87 (dd, J = 13.9, 6.2 Hz, 1H, PfCHH'), 2.70 (m, J = 8.5, 6.2 Hz, IH, H2), 2.07 (m, 2H, H4), 1.82 (m, IH, H3), 1.58 (m, 1H, HY). IR (C=O): v = 1750 cm -1. MS (El): m/z(relative intensity): 308 (M +. 4), 194 (56), 181 (65), 127 (91), 67 (69), 59 (94), 55 (100), 41 (93). HRMS calcd for CI4HI3F502, m/z 308.0836; found 308.0831. 23: 19F NMR (282 MHz, 5, CDCI3): -162.9 (m, Fmeta), -157.0 (t,
Fpara), -143.4/143.5" (m, Fortho); IH NMR (300 MHz, 8, CDCI3): 5.67 (m, 2H, H 3, H4), 3.61/3.60" (s, 3H, COOMe),
2.9-3.1 (m, 2H, PfCH2), 2.62 (m, IH, PfCH2CH), 2.1 (m, 4H, H 2, H5), 1.94 (m, 1H, HI), 1.24-1.45 (m, 2H, H6). IR (C=O): v = 1747 cm -1. MS (El): m/z(relative intensity): 334 (M +, 5), 254 (32), 194 (63), 181 (63), 153 (46), 93 (36), 81 (83), 80 (100), 79 (88), 77 (43), 59 (30), 41 (29). HRMS calcd for C16HI5F502, m/z 334.0992; found 334.0982. *: second diastereoisomer. 24: 19F NMR (282 MHz, 5, CDC13): -163.9 (m, Fmeta),-158.3 (t, Fpara), -144.1 (m, Fortho); IH NMR (300 MHz, 8, CDC13): 6.56 (dd, J = 16.5, 7.3 Hz, IH, PfCH=CH), 6.29 (d, J = 16.5 Hz, IH, PfCH=CH), 5.70 (s, 2H, H l, H2), 2.45 (m, IH, H4), 2.1-2.25 (m, 3H, H 3, H 5, H6), 2.0 (m, 1H, HY), 1.85 (m, IH, H6'), 1.52 (m, 1H, H5'). MS (El): m/z(relative intensity): 274 (M +, 0.86), 181 (5), 151 (18), 80 (100), 41 (7). 25: 19F NMR (282 MHz, 5, CDCI3): -163.0 (m, Fmeta), -157.5 (dt,
Fpara)*, -143.2/143.4" (m,
Fortho); IH NMR (300 MHz, 5, CDC13): 5.36 (b, 1H, H3), 3.61/3.60" (s, 3H, COOMe), 2.62.9 (m, 2H, PfCH2), 1.3-2.4 (m, 7H, H 2, H l, H 5, H6), 1.64 (s, 3H, Me4), 0.91/0.89" (s, 3H, PfCH2C(Me)-). MS (El): m/z(relative intensity): 362 (M +, 10), 181 (81), 149 (53), 107 (100), 95 (82), 79 (81), 74 (67), 68 (75), 67 (99), 55 (51), 41 (46). HRMS calcd for CISHI9F502, m/z 362.1305; found 362.1310. *: two signals corresponding to the mixture of two diastereoisomers.
13864
A. C. AIb(niz et al. / Tetrahedron 54 (1998) 13851-13866
The dienes 26-28 can be separated from 25 by column chromatography (silica gel) eluting with n-hexane. 26: 19F NMR (282 MHz,'5, CDC13): -163.2 (m, Fmeta), -157.7 (t, Fpara), -143.8 (m, Fortho); IH NMR (300 MHz, 8, CDC13): 5.40 is, 1H, H2), 4.85 (s, IH, -C(CH2C6Fs)=CHH), 4.50 (s, IH, -C(CH2C6F5)=CHH), 3.42 is, 2H, -C(CH2C6F5)=CH2), 2.15 (m, IH, H3), 2.0 (m, 1H, H3'), 1.8-2.1 (m, 4H, H 4, H 5, H 6, H6'), 1.66 (s, 3H, Mel), 1.55 (m, IH, H5'). MS (El): m/z(relative intensity): 302 (M +, 6), 181 (51), 121 (95), 93 (99), 91 (53), 79 (83), 77 (65), 68 (100), 67 (97), 53 (97), 41 (52). HRMS calcd for CI6HI5F5, m/z 302.1094; found 362.1087. 27: 19F NMR (282 MHz, 8, CDCI3): -163.9 (m, Fmem), -158.0 (t, Flmra), -140.4 (m, Fortho); IH NMR (300 MHz, 8, CDCI3): 5.86 (b, 2H, H 2, H3), 2.80 (m, IH, PfCHH'), 2.65 (m, 1H, PfCHH'), 2.5 (m, I H, PfCH2CH(Me)-), 1.8-2.4 (m, 4H, H 5, H6) *, 1.66 (s, 3H, Me4) *, 1.06 (d, J
= 6.8 Hz,
3H. PfCH2CH(Me)-). MS (El): m/z: 302 (M+).
*" overlapped with signals of other compounds. 28: 19F NMR (282 MHz, 8, CDCI3): -163.6 (m, Freer,), -158.2 (t, Fpara), -143.7 (m, Fortho); IH NMR (300 MHz, 8, CDC13): 5.4 (b. H3) *, 3.52 (s, 2H, PfCH2), 1.8-2.4 (m, 6H, H 2, H 5, H6) *, 1.6-1.7 (6H, Me 4, PfCH2C(Me)=)*. MS (El): m/z: 302 (M+). *: overlapped with signals of other compounds. 30: 19F NMR (282 MHz, 8, CDCI3): -160.7 (m. Fmem), -148.7 (tt, 3JF-F = 21 Hz, 4JF-F = 4.7 Hz, Fpar,), -138.5 (m, Fortho); IH NMR (300 MHz, 8, CDC13): 3.98 (s, COOMe). MS (El): m/z(relative intensity): 226 (M +, 5), 195 (41), 167 (44), 117 (100), 98 (34), 79 (23). HRMS calcd for C8H3F502, m/z 226.0053; found 226.0055. 31: 19F NMR (282 MHz, 8, CDCI3): -157.9 (m, F 3, F3'), -140.3 (m, F 2, H2'); IH NMR (300 MHz, 8, CDC13): 4.16 (t, 5JH.F = 2.0 Hz, 3H, OMe), 3.96 (s, 3H, COOMe). MS (El): m/z(relative intensity): 238 (M +, 19), 207 (100), 192 (11), 148 (14), 136 (46), 117 (78), 101 (34), 99 (17), 98 (26), 79 (16), 59 (14). HRMS calcd for C9H6F403, m/z 238.0253; found 238.0255. Carbonylation of a mixture of 20 and 7. The above procedure was employed but R-(+)-limonene and [Pd(C6F5)Br(NCMe)2] were reacted at 0 °C for 80 min. A mixture of 201 (14%), 202 (42%), 71 (32%) and 72 (7%) was
obtained as shown by 19F NMR. The final colorless oily residue after the carbonylation procedure was analyzed and it contained 141 (20%), 142 (4%), 25 (5%, mixture of diastereoisomers), 26 (40%), 29 (13%), 28 (4%) and 27 (2%). In addition, unidentified compounds (12% total, each one less than 4%) were found. The products were separated in two batches by column chromatography (silica gel) eluting with n-hexane first (26, 27, 28 and 29) and then diethyl ether (ester derivatives).
A. C. A lbdniz et al. / Tetrahedron 54 (1998) 13851-13866
13865
29: lgF NMR (282 MHz, 8, CDCI3): -163.5 (m, Fmeta),-158.5 (t, Fpara),-143.6 (m, Fortho); IH NMR (300 MHz, 13, CDC13): 5.7 (m, IH, H3), 5.55 (m, 1H, H4), 5.35 (m, 1H, HI), 2.75 (m, IH, PfCHH'), 2.5 (m, IH, PfCHH'), 1.9-1.3 (m, H 5, H 6, PfCH2CH(Me)-) 1.66 (s, 3H, Me2), 0.99 (d, J = 6.7 Hz, 3H, PfCH2CH(Me)-)*. MS (El): m/z: 302 (M+). *: overlapped with signals of other compounds.
Acknowledgments This work was supported by the Direcci6n General de Investigaci6n Cientffica y Tdcnica (Spain) (Project PB96-0363), the Commission of the European Communities (Network "Selective Processes and Catalysis Involving Small Molecules", CHRX-CT93-0147) and the Junta de Castilla y Le6n (Project VA 40-96). Y.-S. L. thanks the Spanish Ministerio de Educaci6n y Ciencia and the A.E.C.l./I.C.D.-Universidad de Valladolid for fellowships.
References [I] Harrington, P. J, in Comprehensive Organometallic Chemistt3": A Review vf the Literature 1982-1994, eds. Abel, E. W.; Stone, F. G. A.; Wilkinson, G. Pergamon Press, Oxford 1995, Vvl 12, Chap. 8.2. [21 Tsuji, J. Palladium Reagents and C~Jtalysis, Wiley: Chichester, 1995. [3] Hegedus, L. S. in Orgam,,etallics in ,~vnthesis (Ed.: M. Schlosser), Wiley, 1994, Chap. 5, [4] De Meijere, A.; IVleyer, F. E. Allgew. Chem. hit. Ed. Ellgl. 1994, 33, 2379. [5] Heck, R. F. Palladimn Reagents in Organic Syntheses; Academic Press: London, 1985. 16] Trost, B. M.; Verhoeven, T. R. in Comprehensive Organometallie Chemistt3", Vol. 8 (Eds.: Wilkinson, G.; Stone, F. G. A.; Abel, E. W.), Pergamon Press, Oxford, 1982, Chap. 57. [71 B/ickvall, J. -E. Adr. Met. Org. Chem. 1989, I. 135. [8] AIb6niz, A. C.; Espinet. P; l_in, Y. -S. Organometallics. 1997, /6, 4138-4144. [9] AIb6niz, A. C.; Espinet. P; l-in, Y. -S. Organometallics, 1995, 14. 2977-2986. [10] AIb6niz A. C.; Espinet, P. Organometallics. 1991, 10, 2987-2988. [ I I I Colquhoun, H. M.; Thompson, D. J.; Twigg, M. V. Carbom'lation: Direct Synthesis of Carbonyl Compounds , Plenum Press, N.Y., 1991. [I 2] Btickvall, J. E.; Nordberg, R. E.; Zettcrberg, K.: ,~kcrmark, B. Organometallics 1983, 2, 1625-1629. [13} Milstein, D. Organometallics 1982, /, 888-890. [14] Hines, l'. F.; Stille, J. K. J. Am. Chem. Soc. 1972, 485-490. [151 Stille, J. K.; Hines, L. F. J. Am. Chem. Soc. 1970, 1798-1799. [161 Ozawa, F.; Son, T.-I.; Osakada, K.; Yamamoto, A. J. Chem. Soc. Chem. Commun. 1989. 1067-1068.
13866
A. C. A lb~niz et al. / Tetrahedron 54 (1998) 1 3 8 5 1 - 1 3 8 6 6
[17] Tsuji, J.; Kiji. J.; Morikawa, M. Tetrahedron Lett. 1963. 26, 1811-18[3. [18] Tsuji. J.; lmamura, S.; Kiji, J. J. Am. Chem. Soc. 1964.86, 4491. [19] Long, R.: Whillield, G. H. J. Chem. Soc. 1964, 1852-1853. [20] Shimizu, 1.: Maruyama. T.: Makuta, T.: Yamamoto, A. Tetrahedron Left. 1993, 34 (13]. 2135-2i38. [21J Wang. S.-Z.; Yamamoto. K.: Yamada, H.: Takahashi, T. Tetrt~hedron 1992.48 (12), 2333-2348. [22]Tsuji. J.;Sato. K.;()kumoto, H.J, Org. Chem. 1984.49. 1341-1344. [23] Tsuji, J.: Hosaka, S. J. Am. Chem. Sot'. 1965. 4075-4079. [24] Brewis, S.; Hughes. P. R, J. Chem. Sot'. Chem. Commlm. 1965, 157-158. (25] Tsuji, J.; Kiji, J.; Imamura, S.: /vlorikawa. M. J. Am. Chem. Soc. 1964, 86, 4350-4353. [26] Hosokawa. T.: Maiflis, P. M. J. Am. Chem. Soc. 1973. 4924-4931. J27] Carluran. G.: Graziani. M.: Ros, R.; Belluco, U. J. Chem. Soc. Dalton Trans 1972, 262-265. [28] AIb,Sniz, A. C.: Espinel, P.: Foccs-Foces, C.: Cano, F. H. Orgamm~etallics 1990, 9, 1079-1085. [29] Alb,5.niz. A. C.; Espinet. P.: Jeannin, Y.; Philoche-Levisalles, M.: /Vlann. B. E. J. Am. Chem. Soc.. 1990, 112. 6594-6600. [30] March, J. Advalwed Orgatlic Chemistt T. Wiley: New York. 1992; p. 586. [3l] James. D. E..Stille. J. K.J. Am. Chem. Soc. 1976, 1810-1823.
Pergamon
Study of Pd-elimination under carbonylation conditions: Regioselective formation of esters Ana C. Albdniz, Pablo Espinet*~ and Yong-Shou Lin Depal*amento de Quimica Inorgdnica. Facultad de Ciencias. Universidad de Valladolid. 47005 Valladolid. Spain.
Received 21 May 1998; revised 3 September 1998; accepted 10 September 1998
Abstract The regioselective synthesis of methyl esters is achieved by carbonylation of two different types of organometallic derivatives resulting from insertion of non-conjugated dienes into a Pd-aryl bond. When the diene and the Pd-aryl synthon [PdPfBr(NCMe)2] (Pf = C6F5) are mixed at low temperature, solutions of 111_112_ enylpalladium complexes can be isolated and converted into ~3-aryl methyl esters by reaction with CO in the presence of methanolic solutions of sodium methoxide. When the reactions are carried out at room temperature q3-allylpalladitm~ complexes are isolated, and their carbonylation gives 13,y-unsaturated esters. © 1998 Elsevier Science Ltd. All rights reserved. Keywords: Palladium and compounds; carbonylation;regiocontrol
Introduction Palladium complexes provide excellent selectivity in the functionalization of dienes [ 1-7]. Nucleophilic attack to the diolefin (trans addition of Pd and the nucleophile), or insertion of one double bond into a Pd-R bond (cis addition) gives organometallic intermediates, usually rl3-allylpalladium complexes, that can be transformed into useful organic compounds (Scheme 1) [7]. The latter process can be referred to as a Pd-elimination process incorporating an X group in place of the palladium atom. The whole process can be carried out catalytically producing functionalized alkenes.
I
e-mail: [email protected]
0040-4020/98/$ - see front matter © 1998 Elsevier Science Ltd. All rights reserved. PII: S0040..4020(98)00852-7
13852
A. C. Albdniz et al. /Tetrahedron 54 (1998) 13851-13866
y-
/
x
Pd
.
\
Pd-Y Scheme 1
When the diolefin is a non-conjugated one, a number of Pd-H eliminations and readditions must occur (palladium migration) before the formation of the corresponding q3_ allyl derivative. Previous works show that, in appropriate systems and conditions, this palladium migration can take periods within the range of time used in the manipulation of an organic synthesis [8-10], and rl l-q2-enylpalladium complexes (A, Scheme 2) can be observed at low temperature as intermediates in the formation of the more stable rl3-allyl derivatives (B, Scheme 2). It should be possible to produce organic products derived either from A or from B (Scheme 2), provided that the Pd-elimination reaction chosen does not induce a fast Pd-migration. To test the feasibility of this idea a fast and efficient, as well as selective Pdelimination procedure was chosen: The substitution of palladium for an ester group.
--Pd-R
,
.
x
A
X
Pd-migration
/
Pd
\
X
~
R
Scheme 2
Carbonylation reactions assisted by transition-metal complexes have become an efficient method for the direct introduction of a carbonyl functional group into an organic molecule [5,11]. The reaction is stereoselective and occurs with retention of configuration at the former Pd-bound carbon [12-15]. The synthesis of carbonyl compounds from rl3-allylpalladium complexes has been carried out both as a stoichiometric reaction [12,13,16-19] or in a catalytic process involving rl3-allylpalladium intermediates [20-25]. There have also been a number of reports on the carbonylation of 111-rl2-enylpalladium complexes [ 14,26,27]. We
A. C. AIb(niz et al. / Tetrahedron 54 (1998) 13851-13866
13853
report here the use of the carbonylation reaction in a regio-controlled synthesis of esters from either rl l-rl2-enyl or rl3-allylpalladium complexes.
Results and Discussion
The carbonylation of the organometallic palladium derivatives was carried out by bubbling carbon monoxide through a solution of the palladium complex and sodium methoxide in CHC13/MeOH. The rl3-allylpalladium derivatives employed were prepared by reaction of [PdPfBr(NCMe)2] (Pf = C6F5) and the suitable diene at room temperature [810,28]. They are collected in Table 1, along with their corresponding organic esters. The rl 1_ q2-enyl complexes 17, 18, 19 and 20, intermediates in the formation of 1, 2, 6, and 7 from non-conjugated dienes, can be prepared in solution at low temperature, and are collected in Table 2 as well as their carbonylation products. Table 1. Carbon vlation of (q3-allvl)palladium complexes a Entry Diene b Complex
Pd 2
~
~
Product
Yield(%) c
~ P f
(5)
~ P f COOMe Me,,.~ MeOOC~R
(9)
COOMe P
f
(2)
Pd Pd
Me
95 96
H P f
Me (101)°
83
(111)cl
88
Pf--@COOMe
(121)d
92
~PIC2Hd"~
(13a)
48
Pf PI.--~ I
I
COOMe
PICH2/
MeOOC 48
PfC2Hd.-~ C O O M o (13b)
800
PfCH~'~
COOMo cH2Pf
(15)
a) Pf = C6F5; reaction conditions: (q3-allyl)palladium complex (0. I mmol) and NaOMe (0.6 mmol) in CHCI3/MeOH solution ( I:1 ) was saturated with CO (I atm) and reacted for 20 min at room temperature; b) Dienes used in the preparation of the (q3_ allyl)palladium complexes (see ref. 8-10, 28); c) determined by integration of 19F NMR signals; the remaining 4-5% in entries I, 2, 6 and 7 corresponds to a small amount of esters which could not be identified due to overlap of their I H NMR signals; d) mixed with unreacted starting q3-allyl complex: 17% for entry 3, 12% for entry 4, 8% for entry 5 and 12% for entry 7; e) isolated yield for 14 is 58%.
A. C. A lbt;niz et al. / Tetrahedron 54 (1998) 1385 I - 13866
13854
The major product in the carbonylation of the rl3-allylpalladium complexes in the presence of base (NaOMe) is a [3,),-unsaturated monoester. High regioselectivity is observed and insertion of CO occurs,at the less substituted allylic carbon (entries 1 and 2, Table 1) or the less hindered position (entries 3, 5 and 7, Table 1). The same selectivity has been reported before for the carbonylation of q3-allylpalladitml derivatives, both under mild conditions [13,16] or under high-pressure [17-19,23-25]. In every case, about 4% of unidentified ester compounds were detected which might correspond to carbonylation at the most substituted terminal allylic carbon. The formation of two isomeric esters in an approximate ratio 1:1 derived from 6 (entry 6, Table 1) reflects their close substitution pattern. The influence of the bulky C6F5 group, three carbons away from the allylic moiety, is negligible in this case but important in complex 5, where pentafluorophenyl is only one carbon apart and selective carbonylation occurs. The opposite regioselectivity (CO incorporation into the more substituted carbon) was found in the carbonylation of a complex analogous to 5 but showing trans Pd-OMe stereochemistry, di-g-chlorobis[(4-methoxy-l-3-q3-cyclohexenyl)dipalladium(lI), to trans-3-((diethylamino)carbonyl)-4-methoxy-l-cyclohexene in the presence of diethylamine [12]. In this case insertion of CO into the Pd-C seems to be favored when the methoxy group is in a [3-position. A Pd-H elimination product, 15 (4%), was formed in the carbonylation of 7. It could be formed by [3-H elimination in an q l-allyl intermediate with C-1 bound to palladium. The endo sterochemistry of the attack of the pentafluorophenyl group to a cyclic diene double bond has been confirmed by X-ray structure determinations of the palladium complexes formed [28,29]. Thus, the cyclic rl3-allylpalladium derivatives 4 and 5 show cis Pd-Pf
stereochemistry.
Compounds
6 and 7 are expected to be t r a n s due to the
stereochemistry of Pd-migration (cis-elimination-readditions). On the other hand, the carbonylation reaction is known to proceed with retention of configuration, and accordingly only one diastereoisomer (cis) was found in the esters derived from 4 and 5 (111 and 121, respectively). A trans arrangement is expected and proposed for the cyclohexene esters 13a, 13b and 14 (the latter as a mixture of the two diastereoisomers found in the starting material) [9], but their configuration could not be confirmed unequivocally because the high complexity of their IH NMR spectra prevented the measurement of vicinal coupling constants. The q3-allylpalladium complex 3, formed by insertion of trans,trans-2,4-hexadiene into the Pd-Pf bond, is obtained as a single diastereoisomer [28], and only one ester was obtained from it as a single diastereoisomer (101). Some unreacted q3-allylpalladium complex accompanied the final organic esters in some of these reactions (see entries 3-5, 7, Table 1). Addition of a larger amount of base (molar ratio: rl3-allyl/NaOMe = 1/12, instead of the usual 1/6) brought about the complete
A. C. AIb&d2. et al. / Tetrahedrm, 54 (1998) 13851-13866
13855
carbonylation of the starting materials, but lead to the epimerization of the final esters. Thus, the diastereoisomers 102 (25%), 112 (trans, 15%) and 122 (trans, 38%) were obtained.: The racemization of unsaturated esters in the presence of base by cz-deprotonation is a known process and the new diastereoisomers could result from the isomerization of the cis derivatives 111 and 121, or 101 [14,30]. This was confirmed when epimerization of ester 121 was actually observed upon addition of sodium methoxide. The formation of 102 might also be interpreted as a result of svn-anti isomerization of the methyl substituted allylic carbon in the starting palladium derivative 3: Carbonylation of 1-anti-2-svn-3 would give 102. However, svn-anti isomerization has not been observed in other carbonylation experiments or in the same experiment with less base; this leaves the base-promoted epimerization as the most likely cause of the formation of 102 [14].
MeOOC Me~ ~
H P
H
102
f
{~
OMe COOMe
Me pf
Pf
112
122
Pf = C6F5
The r I l-rl2-enyls 17, 18, 19 and 20 were prepared in situ by reaction of 1,5-hexadiene, 1,6-heptadiene, 4-vinyl-l-cyclohexene and R-(+)-limonene with [PdPfBr(NCMe)2] at low temperature in CH~CI'~ (see Table 2) [8-10]. 17 can also be isolated as a white solid by crystallization from Et20 when the arylation reaction is carried out at 0 °C for 5 min [10]. The relative rates of the insertion reaction of the diene into the Pd-Pf bond, coordination of the unattacked double bond to give the rl l-q2-enyl, and Pd-migration to form the final allyl derivatives, prevented the "in situ" preparation of pure solutions of the rl l-rl2-enyl complexes [8]. Some starting [PdPfBr(NCMe)2] complex and allyl derivatives were also present and, when the carbonylation reaction was carried out, the corresponding ester derivatives were obtained, which could be easily identified by NMR (Table 2). cx-Alkenyl pentafluorophenylpropanoic methyl esters were obtained in high yield in the carbonylation reactions of the linear q l-rl2-enylpalladium derivatives 17 and 18 (entries 1 and 2, Table 2). The same type of ester (23) was obtained as a major compound in the carbonylation of complex 19, although mixed with the esters derived from the corresponding allyl derivative and a Pd-H elimination product, 24 (entry 3, Table 2). Compound 23 is a 1:1 mixture of diastereoisomers, reflecting the ratio found for the starting complex 19.
2 A Pd-H elimination product E,E-2-(pentafluorophenyl)-2,4-hexadiene (16) which comprises 5% of the mixture is also observed in tile carbonylation reaction of 3 with excess base (3:NaOMe = 1:12), along with the diasteroisomers 101 (70%) and 102 (25%).
A. C. Alb~niz et al. / Tetrahedron 54 (1998) 1 3 8 5 1 - 1 3 8 6 6
13856
5
o
,,z,
E o
o
d
n
I
g
:
"6
© 0
o..
m
G
t'N
~0
Lt.
-
~
i e-
I
~
.-~
&
E
~ ¢"~. -4-
c "-
.:
g
~
"_~
p_
o
._o
2
~4
L Z ~ " l "; ±
E 0
tl'3
o
o
t'N
cq
~R
v
'5
15
i - o ~
S-~_
I=
.-=~.=_
.o
o z Z
~
~u_~
~
~- e,.I
t-..i
Io ~.o_=o I-=
,,_, = e-
~--~
~=g,-....
=
=
o~
•
e-
I
+
E r-,
4
i..
~..,:. ~
u
g,
e.i ¢-
.i.1
~
o ~.---~
._.-.-...~
A. C. AlbEniz et al. / Tetrahedron 54 (1998) 13851-13866
13857
The carbonylation reaction of the diastereomeric mixture of rll-rl2-enylpalladium complexes derived from limonene (201,202) at 253 K (entry 4, Table 2) [9] produced, by [5H elimination, the diene 26 as the major compound. In addition, two other [5-H elimination compounds (27, 28) were detected as minor products. Only small percentages of the methyl esters 251 and 252 were formed. Thus, this compound is reluctant to insertion of CO into the Pd-carbon bond, as found for other Pd-bound tertiary carbons, which do not undergo CO insertion [31]. The presence of carbon monoxide only promotes the [5-H elimination and the decoordination of the dienes formed in this way. [5,3,-unsaturated esters arising from the small amount of rl3-allyl derivatives present in the starting solutions (see above) were detected in each reaction (except for complexes 71 and 72 which do not react under the carbonylation conditions used in entry 4, Table 2). When some [PdPtBr(NCMe)2] is also present it gives methyl pentafluorobenzoate (30), and/or methyl 2,3,5,6-tetrafluoro-4-methoxy benzoate (31), resulting from nucleophilic substitution by methoxide of the activated Fpara in the aromatic ring on compound 30. The starting ratios r 1l-rl2-enyl:rl3-allyl are roughly maintained in their corresponding carbonylation products for every enyl derivative (Table 2), showing that Pd-migration is not promoted under the carbonylation conditions. When CO insertion is not a facile process, such as observed for complexes 20, [5-H elimination occurs followed by displacement of the newly formed dienes. The isomerization of the r I i-q2-enylpalladium complexes formed from R-(+)-limonene to the corresponding q3-allyl derivatives is diastereoselective: Complexes 201 and 202 isomerize with different activation energies and, by controlling the temperature, it is possible to have a solution mixture with 202 and the allyl derivative 71 as major products (the configuration of both diastereoisomers has been assigned on the basis of steric arguments, but could not be determined unequivocally) [9]. Carbonylation of a mixture of 201,202, 71 and 72 in the ratio shown in Scheme 3, obtained by reaction of R - ( + ) - l i m o n e n e and [PdPfBr(NCMe)2] at 273 K for 80 rain, gave the ester derivatives: 141, 142 and 25 (mixture of two diastereoisomers 251 and 252) in a 4:1:1 ratio. Since CO insertion into the Pd-tertiary carbon bonds of the 11l-q2-enylpalladium derivatives 201 and 202 is disfavored, the rest of the products obtained were [3-H elimination compounds (26, 2-methyl-5-[l'-methyl-l'(pentafluorophenylmethyl)]-methyl-l,3-cyclohexadiene (29) and a small amount of 27 and 28). They could be easily separated from the methyl esters by column chromatography. Thus, ester 141 is obtained as a single enantiomer with three asymmetric centers in 67% diastereomeric excess.
13858
A, C. Alb#niz et al. /Tetrahedron 54 (1998) 13851-13866
[PdPfBr(NCMe)2] Pf = C6F5 273 K 80 min 5
5
H CH3'"" 1 PfCH 2
r
I
l
PfCH2'""J
2"
2oi (14%)
I 2'
292 (42°1o)
H~ - -
+ PfCH 2
I
CH 3
PcI://~Y "\
H
71 (32'=/0)
72 (7%) 273 K CO NaOMelMeOH
~ ~
H2Pf
~
Me
CH2Pf
COOMe
COOMe
141 (2o°/o)
+
26 (40%)
e
+
+
_••H2Pf
Me COOMe
142 (4%)
+
27 (2'/o)
+
28 (4%)
2,5 (5%) +
~ H 2 P f
29 (130) Scheme 3
Conclusions The formation of intermediate r II-q2-enylpalladium complexes at low temperature, which arrest the Pd-migration process to form the thermodynamically more stable q3-allyl derivatives, can be advantageously used in the regioselective functionalization of the organic moiety. Thus, carbonylation reactions carried out on either type of derivative afford two
A. C. A lb~niz et al. / Tetrahedron 54 (1998) 13851-13866
13859
types of regioisomeric unsaturated methyl esters. This selection is possible because CO reacts fast and does not promote Pd-migration, thus the rl3-allyl complex is not formed from the rl 1_ rl2-enylpalladium derivative during the carbonylation process.
Experimental Section General Considerations. The yellow complexes 1 [8,10], 2 [8], 3 [28], 4 [28], 5 [28], 6 [9], 7 [9], 17 [8,10], and pale yellow solutions containing the r II-rl2-enylpalladium complexes 18 [8], 19 [9], and 20 [9],were prepared as reported in the literature. The diolefins employed were purchased from Aldrich, Lancaster or Janssen and used without further purification. IH and 19F NMR spectra were obtained on Bruker AC-300 and ARX-300 spectrometers at 293 K unless otherwise noted. Proton and carbon chemical shifts were referenced to TMS and 19F chemical shifts to CFCI3. Double irradiation and proton homonuclear correlation experiments were carried when necessary. IR spectra (Nujol mulls) were recorded on a Perkin-Elmer 883 spectrometer. Organic products were analyzed using an HP-5890 gas chromatograph connected to an HP-5988 mass spectrometer at an ionizing voltage of 70 eV and a quadrupole analyzer. Evaporation of solvents was carried out using a water pump to avoid evaporation of low boiling point organic derivatives of interest. Relative percentages of compounds formed are calculated according to the integration of 19F NMR signals; an error of _+ 0.5 % is assumed due to proximity of the resonances or spectral noise in the case of products with low abundance.
Carbonylation of the rl3-allylpalladium complexes. Carbonylation of 1. To a solution of the yellow complex 1 (0.052 g, 0.06 mmol) in CHC13 (10 mL) was added NaOMe (0.019 g, 0.36 retool) in anhydrous methanol (10 mL) at room temperature. CO was immediately bubbled through the mixture for 20 rain and palladium precipitated. The palladium metal was filtered and the filtrate was evaporated to dryness using a water pump. The residue was triturated with diethyl ether and filtered. Evaporation of the solvent gave a colorless oily residue, 8 (yield: 95%, determined by 19F NMR). The same procedure was employed for the carbonylation of complexes 2, 3, 4, 5, 6 and 7. The esters were obtained as colorless oily residues in every case and the yields are collected in Table 1. Additional purification procedures were used in some cases and they are described below. Carbonylation of complexes 3, 4, and 5 using double amount of NaOMe (0.038 g, 0.72 mmol) was carried out in the same way (see Results and Discussion). Diastereoisomers were not separated and they were characterized as a mixture in each case.
13860
A. C. A Ib~niz et al. / Tetrahedron 54 (1998) 13851-13866
8: 19F NMR (282 MHz, 5, CDCI3): -163.5 (m, Fmeta), -158.5 (t, Fpara), -144.8 (m, Fortho); IH NMR (300 MHz, 8, CDCI3): 5.56 (m, 2H, H 3, H4), 3.68 (s, 3H, COOMe), 3.04 (d, J = 4.9 Hz, 2H, H2), 2.68 (tt, J = 7.6, 4JH.F = 1.4 Hz, 2H, HT), 2.08 (m, 2H, H5), 1.66 (qui, J = 7.5 Hz, 2I-1, H6). IR (C=O): v = 1753 cm -1. MS (El): m/z(relative intensity): 308 (M+,6), 276 (37), 194 (16), 181 (67), 68 (35), 67 (28), 59 (100), 53 (20), 41 (14). HRMS calcd for CI4HI3F502, m/z 308.0836; found 308.0835. 9: 19F NMR (282 MHz, 5, CDCI3): -163.5 (m, Fmeta), -158.7 (t, Fpara), -144.9 (m, Fortho); 1H NMR (300 MHz, 8, CDCI3): 5.52 (m, J = 5.8, 1.0 Hz, 2H, H 3, H4), 3.68 (s, 3H, COOMe), 3.03. (dd, J = 5.8, 1.0 Hz, 2H, H2), 2.68 (tt, J = 7.5, 4JH-F = 1.6 Hz, 2H, HS), 2.06 (m, J = 7.3 Hz, 2H, H5), 1.57 (qui, J = 7.3 Hz, 2H, HT), 1.42 (qui, J = 7.3 Hz, 2H, H6). IR (C=O): v = 1752 cm -1. MS (El): m/z(relative intensity): 322 (M+,2), 194 (20), 181 (100), 141 (14), 119 (14), 109 (17), 96 (15), 81 (33), 74 (43), 67 (19), 58 (35), 41 (14). HRMS calcd for C I5HIsFsO2, m/z 322.0992; found 322.1004. 101: 19F NMR (282 MHz, 8, CDC13): -163.0 (m, Fmeta), -158.11 (t, Fpara), -143.3 (m, Fortho); IH NMR (300 MHz, 5, CDCI3): 5.77 (dd, J = 15.3, 6.9 Hz, IH, H3), 5.65 (dd, J = 15.3, 7.5 Hz, 1H, H4), 3.89 (m, J = 7.2, 6.9 Hz, 1H, H2), 3.67 (s, 3H, COOMe), 3.12 (m, J = 7.5, 7.1 Hz, 1H, H5), 1.41 (d, J = 7.2 Hz. 3H, Me), 1.25 (d, J = 7.1 Hz, 3H, H6). IR (C=O): v = 1751 cm -1. MS (El): m/z(relative intensity): 308 (M +, 24), 249 (51), 248 (40), 233 (36), 221 (39), 207 (58), 195 (28), 187 (25), 181 (100), 88 (71), 59 (46), 55 (20). HRMS calcd for C14H13F502, m/z 308.0836; found 308.0845. 102: 19F NMR (282 MHz, 5, CDC13): -163.0 (m, Fmeta), -158.09 (t, Fpara), -143.3 (m, Fortho); IH NMR (300 MHz, 5, CDC13): 5.77 (dd, J = 15.3, 6.9 Hz, 1H, H3) *, 5.65 (dd, J = 15.3, 7.5 Hz, IH, H4) *, 3.89 (m, J = 7.2, 6.9 Hz, 1H, H2) *, 3.68 (s, 3H, COOMe), 3.12 (m, J 7.1 Hz, 1H, HS) *, 1.41 (d, J = 7.2 Hz, 3H, Me)*, 1.23 (d, J = 7.1 Hz, 3H, H6). IR
= 7.5,
(C=O): v = 1751 cm-l. *: overlapped with signals of 101 111: 19F NMR (282 MHz, 5, CDCI3): -162.8 (m, Fmeta), -157.6 (t, Fpara), -143.2 (m, Fortho); IH NMR (300 MHz, 8, CDCI3): 5.85-5.9 (m, 2H, H 2, H3), 3.71 (s, 3H, COOMe), 3.34 (m, 2H, H l, H5), 2.1-2.5 (m, 4H, H 4, H6). IR (C=O): v = 1750 cm -1. MS (El): m/z(relative intensity): 306 (M +, 17), 274 (16), 247 (63), 246 (62), 194 (17), 181 (96), 66 (16), 59 (100), 51 (11). HRMS calcd for CI4HI IF502, m/z 306.0679; found 306.0692. 112: 19F NMR (282 MHz, 5, CDCI3): -163.0 (m, Fmeta), -157.9 (t, Fpara), -143.1 (m, Fortho); I H NMR (300 MHz, 5, CDC13): 5.8-5.9 (m, 2H, H 2, H3) *, 3.73 (s, 3H, COOMe), 3.34 (m, 2H, H l, HS) *, 2.1-2.5 (m, 4H, H4, H6) *. IR (C=O): v = 1750 cm -1. *: overlapped with signals of 111. 121: 19F NMR (282 MHz, 5, CDCI3): -163.0 (m, Fmeta), -157.7 (t, Fpara), -143.1 (m, Fortho); IH NMR (300 MHz, ~5, CDCI3): 5.98 (m, J = 10.0, 4.8, 2.8 Hz, 1H, H2), 5.74 (m, J = 10.0,
A. C. A lb~niz et al. / Tetrahedron 54 (I 998) 13851-13866
13861
2.2, 0.9 Hz, IH, H3), 3.8 (m, J = 2.8, 2.2 Hz, 1H, HI), 3.72 (s, 3H, COOMe), 3.16 (m, J = 4.8, 0.9 Hz, IH, H4), 2.29 (m, 1H, H5), 1.90 (m, 2H, H6), 1.81 (m, 1H, HS'). IR (C=O): v = 1746 cm -1. MS tEl): m/z(relative intensity): 306 (M +, 9), 247 (39), 246 (90), 181 (100), 169 (10), 79 (197, 77 (36), 66 (12), 59 (92), 53 (16), 51 (187. HRMS calcd for CI4HIIF502, m/z 306.0679; found 306.0673. 122: 19F NMR (282 MHz, 8, CDC13): -162.9 (m, Fmeta), -157.6 (t, Fpara), -143.5 (m, Fortho); IH NMR (300 MHz, 8, CDCI3): 5.98 (m, 1H, H2), 5.74 (m, 1H, H3) *, 3.8 (m, 1H, HI) *, 3.72 (s, 3H, COOMe)*, 3.27 (m, IH, H4), 2.2 (m, IH, H5), 2.05 (m, 1H, H6), 1.75-2.0 (m, 2H, H 6', H5'). IR (C=O): v = 1746 cm -1. • : overlapped with signals of 121. 13a: 19F NMR (282 MHz, 5, CDCI3): -163.3 (m, Fmeta), -158.4 (t, Fpara), -145.1 (m, Fortho); tH NMR (300 MHz, ~5, CDCI3): 5.86 (m, 1H, H3), 5.59 (m, H, H2), 3.69 (s, 3H, COOMe), 2.89 (m, 1H, HI), 2.74 (t, J = 7.4 Hz, 2H, PfCH2)*, 1.9-2.15 (m, 4H, H 4, H 5, H6) *, 1.45-1.7 (m, 2H, PfCH2CH2)*, 1.38 tin, IH, H5'). IR (C=O): v = 1750 cm -1. MS** tEl): m/z(relative intensity): 334 (M +, 32), 275 (48), 274 (66), 181 (1007, 93 (82), 81 (38), 79 (67), 77 (37), 67 (29), 41 (9). HRMS calcd for CI6HI5F502, m/z 334.0992; found 334.1002. • : overlapped with signals of 13b. 13b: 19F NMR (282 MHz, 8, CDC13): -163.3 (m, Fmeta), -158.4 (t, Fpara), -145.0 (m, Fortho); IH NMR (300 MHz, 5, CDCI3): 5.7-5.85 (m, 2H, H 2, H3), 3.70 (s, 3H, COOMe), 3.11 (m, IH, HI), 2.74 (t, J = 7.4 Hz, 2H, PfCH2)*, 1.9-2.15 (m, 3H, H 4, H 5, H6) *, 1.76 (m, 1H, H6'), 1.45-1.7 (m, 2H, PfCH2CH2)*, 1.30 (m, IH, HS'). IR (C=O): v = 1750 cm -1. MS** (El): m/z(relative intensity): 334 (M +, 2), 275 (21), 274 (38), 181 (42), 93 (100), 79 (38), 77 (22), 41 (4). HRMS calcd for Ct6HI5FsO2, m/z 334.0992; found 334.1002. • : overlapped with signals of 13a • *: MS spectra for 13a and 13b could be reversed since it was not possible to distinguish them. Preparative TLC (silica gel) with n-hexane/EtOAc (9:1) as eluent was used for the separation of the diastereomeric mixture of esters 14 (Rf = 0.6, isolated yield: 58%) from unreacted Pd complex which is soluble in diethyl ether. 141: 19F NMR (282 MHz, 5,-CDC13): -163.4 (m, Fmem), -158.2 (t, Fpara), -143.7 (m, Fortho); IH NMR (300 MHz, 5, CDC13): 5.29 (b, IH, H2), 3.72 (s, 3H, COOMe), 3.17 (m, J = 8.5 Hz, IH, HI), 2.75 (db, J = 13.3 Hz, 1H, PfCHH'), 2.39 (dd, J = 13.3, 11.7 Hz, IH, PfCHH'), 1.95-2.1 (m, J = 8.5 Hz, 3H, H 4, H6), 1.73-1.9 (m, 2H, H5, PfCH2CH(Me)-), 1.70 (sb, 3H, Me3), 1.45 (m, 1H, H5'), 0.86 (d, J = 6.8 Hz, 3H, PfCH2CH(Me)-). IR (C=O): v = 1748 cm -1. MS (El): m/z(relative intensity): 362 (M +, 3), 181 (76), 121 (65), 93 (88), 91 (54), 81 (100), 79 (74), 77 (64), 59 (63), 41 (30). HRMS calcd for CI8HI9F502, m/z 362.1305, found 362.1303.
13862
A. C. Alb6niz et al. / Tetrahedron 54 (1998) 13851-13866
142: 19F NMR (282 MHz, 8, CDCI3): -163.3 (m, Fmeta), -158.0 it, Fpara), -144.0 (m, Fortho); IH NMR (300 MHz, 8, CDC13): 5.24 (b, 1H, H2), 3.62 (s, 3H, COOMe), 3.05 (m, J = 8.5 Hz, IH, HI), 2.73 (dd, J = 15.{), 9.2 Hz, IH, PfCHH'), 2.61 (dd, J = t5,0, 5.8 Hz, IH, PfCHH'), 1.95-2.1 (m, 2H, H4) *, 1.73-1.9 (m, J = 8.5 Hz, 3H, H6, H 5, PfCH2CH(Me)-)*, 1.67 (s, 3H, Me3), 1.33 (m, IH, H5'), 0.86 (d, J = 6.8 Hz, 3H, PfCH2CH(Me)-)*. IR (C=O): v = 1748 cm1. MS (El): m/z(relative intensity): 362 (M +, 3), 181 (46), 121 (55), 93 (81), 91 (46), 81 (100), 79 (65), 77 (60), 59 (47), 41 (32). HRMS calcd for CISHI9F502, rrdz 362.1305, found 362.1303. *: overlapped with signals of 141.
15: Colorless oil. It can be separated by silica gel colunm chromatography eluting with nhexane. 19F NMR (282 MHz, 8, CDC13): -163.4 (m, Fmeta), -158.2 (dr, Fpara)*, -143.6 (m, Fortho); 1H NMR (300 MHz, 8, CDCI3): 6.23 (m, J = 10. I Hz, 1H, H2), 5,65-5.8 (m, J = 10.1 Hz, 1H, H3), 4.80 (b, 2H, CH2=), 2.76 (m, IH, PfCHH'), 2.45-2.6 (m, 3H, H4, H 6, PfCHH'), 2.3 (m, IH, H6'), 1.87 (m, J = 6.8 Hz, IH, PfCH2CH(Me)-), 1.5-1.6 (m, 2H, H5), 0.87/0.85 (d, J = 6.8 Hz, 3H, Me)*. MS (El): m/z(relative intensity): 302 (M+, 4), 181 (20), 121 (31), 93 (100), 91 (70), 79 (34), 77 (75), 65 (29), 53 (22), 51 (21), 41 (32). HRMS calcd for C|6HI5F5, m/z 302.1094; found 302.1087. *: two signals corresponding to the mixture of two diastereoisomers. 16: Colorless oil. It was separated by column chromatography (silica gel) using n-hexane as eluent. 19F NMR (282 MHz, 8, CDC13): -163.3 (m, Fmeta), -157.9 (t, Fpara), -142.6 (m, Fo,.tho); 1H NMR (300 MHz, 8, CDC13): 6.40 (m, J = 15.0, 10.8 Hz, 1H, H4), 6.11 (d, J = 10.8 Hz, 1H, H3), 5.85 (m, J = 15.0, 6.9 Hz, 1H, H5), 2.05 (s, 3H, HI), 1.85 (d, J = 6.9 Hz, 3H, H6). MS (El): m/z(relative intensity): 248 (M +, 47), 233 (100), 218 (12), 213 (17), 187 (13), 183 (19), 181 (39), 169 (12), 143 (10), 51 (8).
Carbonylation of the ql-q2-enylpalladium complexes. Carbonylation of 18. [Pd(C6F5)Br(NCMe)2] (0.050 g, 0.115 retool) in CH2CI2 (10 mL) was cooled to -30 °C, and 1,6-heptadiene (0.0155 mL, 0.115 retool) was added. The mixture was kept at that temperature for 50 rain. After this time a pale yellow solution containing 18 (91%), the allyl derivative 2 (3%) and [Pd(C6F5)Br(NCMe)2] (6%) was obtained as shown by 19F NMR. A solution of NaOMe (0.037 g, 0.690 retool) in anhydrous MeOH (10 mL) at -30 °C was added to the mixture. Carbon monoxide was immediately bubbled through the solution for 20 min at that temperature. After warming to room temperature and filtering off the palladium metal, the solution was evaporated and residue was triturated with Et20. The suspension was filtered and the filtrate was evaporated to dryness; a colorless oily residue was obtained (24 mg), which was a mixture of 22 (86%), 9 (5%), C6Fs-COOMe (30, 5%) and unidentified esters (4%).
A. C. Albc;niz et al. / Tetrahedron 54 (1998) 13851-13866
13863
22: 19F NMR (282 MHz, 8, CDCI3): -162.9 (m, Fmeul), -156.9 (t, Fpara), -143.3 (m, Fortho); IH NMR (300 MHz, 5, CDC13): 5.75 (m, IH, H6), 4.96 (m, 2H, H7), 3.65 (s, 3H, COOMe), 3.01 (dd, J = 14.0, 8.6 Hz, IH, PfCHH'), 2.85 (dd, J = 14.0, 6.3 Hz, IH, PfCHH3, 2.68 (m, J = 8.6, 6.3 Hz, 1H, H2), 2.05 (q, J = 7.3 Hz, 2H, HS), 1.69 (m, 1H, H4), 1.51 (m, 1H, H4'), 1.42 (m, 2H, H3). IR (C=O): v = 1750 cm -1. MS (El): m/z(relative intensity): 322 (M +, 13), 254 (57), 221 (19), 194 (79), 181 (100), 141 (27), 81 (17), 69 (19), 59 (17), 55 (16), 41 (18). HRMS calcd for CI5HI5F502, m/z 322.0992; found 322.0997. Table 2 lists the conditions used to generate solutions containing 17, 19 or 20 and their composition. Carbonylation reactions were carried out on these solutions as indicated above for complex 18 to obtain colorless oily residues that contained the products collected in Table 2. Mixtures of products were not separated except when noted. 21: 19F NMR (282 MHz, 8, CDC13): -163.0 (m, Fmeta), -156.9 (t, Fpara), -143.3 (m, Fortho); IH NMR (300 MHz, 8, CDC13): 5.73 (m, IH, H5), 4.99 (m, 2H, H6), 3.64 (s, 3H, COOMe), 3.01 (dd, J = 13.9, 8.5 Hz, IH, PfCHH'), 2.87 (dd, J = 13.9, 6.2 Hz, 1H, PfCHH'), 2.70 (m, J = 8.5, 6.2 Hz, IH, H2), 2.07 (m, 2H, H4), 1.82 (m, IH, H3), 1.58 (m, 1H, HY). IR (C=O): v = 1750 cm -1. MS (El): m/z(relative intensity): 308 (M +. 4), 194 (56), 181 (65), 127 (91), 67 (69), 59 (94), 55 (100), 41 (93). HRMS calcd for CI4HI3F502, m/z 308.0836; found 308.0831. 23: 19F NMR (282 MHz, 5, CDCI3): -162.9 (m, Fmeta), -157.0 (t,
Fpara), -143.4/143.5" (m, Fortho); IH NMR (300 MHz, 8, CDCI3): 5.67 (m, 2H, H 3, H4), 3.61/3.60" (s, 3H, COOMe),
2.9-3.1 (m, 2H, PfCH2), 2.62 (m, IH, PfCH2CH), 2.1 (m, 4H, H 2, H5), 1.94 (m, 1H, HI), 1.24-1.45 (m, 2H, H6). IR (C=O): v = 1747 cm -1. MS (El): m/z(relative intensity): 334 (M +, 5), 254 (32), 194 (63), 181 (63), 153 (46), 93 (36), 81 (83), 80 (100), 79 (88), 77 (43), 59 (30), 41 (29). HRMS calcd for C16HI5F502, m/z 334.0992; found 334.0982. *: second diastereoisomer. 24: 19F NMR (282 MHz, 5, CDC13): -163.9 (m, Fmeta),-158.3 (t, Fpara), -144.1 (m, Fortho); IH NMR (300 MHz, 8, CDC13): 6.56 (dd, J = 16.5, 7.3 Hz, IH, PfCH=CH), 6.29 (d, J = 16.5 Hz, IH, PfCH=CH), 5.70 (s, 2H, H l, H2), 2.45 (m, IH, H4), 2.1-2.25 (m, 3H, H 3, H 5, H6), 2.0 (m, 1H, HY), 1.85 (m, IH, H6'), 1.52 (m, 1H, H5'). MS (El): m/z(relative intensity): 274 (M +, 0.86), 181 (5), 151 (18), 80 (100), 41 (7). 25: 19F NMR (282 MHz, 5, CDCI3): -163.0 (m, Fmeta), -157.5 (dt,
Fpara)*, -143.2/143.4" (m,
Fortho); IH NMR (300 MHz, 5, CDC13): 5.36 (b, 1H, H3), 3.61/3.60" (s, 3H, COOMe), 2.62.9 (m, 2H, PfCH2), 1.3-2.4 (m, 7H, H 2, H l, H 5, H6), 1.64 (s, 3H, Me4), 0.91/0.89" (s, 3H, PfCH2C(Me)-). MS (El): m/z(relative intensity): 362 (M +, 10), 181 (81), 149 (53), 107 (100), 95 (82), 79 (81), 74 (67), 68 (75), 67 (99), 55 (51), 41 (46). HRMS calcd for CISHI9F502, m/z 362.1305; found 362.1310. *: two signals corresponding to the mixture of two diastereoisomers.
13864
A. C. AIb(niz et al. / Tetrahedron 54 (1998) 13851-13866
The dienes 26-28 can be separated from 25 by column chromatography (silica gel) eluting with n-hexane. 26: 19F NMR (282 MHz,'5, CDC13): -163.2 (m, Fmeta), -157.7 (t, Fpara), -143.8 (m, Fortho); IH NMR (300 MHz, 8, CDC13): 5.40 is, 1H, H2), 4.85 (s, IH, -C(CH2C6Fs)=CHH), 4.50 (s, IH, -C(CH2C6F5)=CHH), 3.42 is, 2H, -C(CH2C6F5)=CH2), 2.15 (m, IH, H3), 2.0 (m, 1H, H3'), 1.8-2.1 (m, 4H, H 4, H 5, H 6, H6'), 1.66 (s, 3H, Mel), 1.55 (m, IH, H5'). MS (El): m/z(relative intensity): 302 (M +, 6), 181 (51), 121 (95), 93 (99), 91 (53), 79 (83), 77 (65), 68 (100), 67 (97), 53 (97), 41 (52). HRMS calcd for CI6HI5F5, m/z 302.1094; found 362.1087. 27: 19F NMR (282 MHz, 8, CDCI3): -163.9 (m, Fmem), -158.0 (t, Flmra), -140.4 (m, Fortho); IH NMR (300 MHz, 8, CDCI3): 5.86 (b, 2H, H 2, H3), 2.80 (m, IH, PfCHH'), 2.65 (m, 1H, PfCHH'), 2.5 (m, I H, PfCH2CH(Me)-), 1.8-2.4 (m, 4H, H 5, H6) *, 1.66 (s, 3H, Me4) *, 1.06 (d, J
= 6.8 Hz,
3H. PfCH2CH(Me)-). MS (El): m/z: 302 (M+).
*" overlapped with signals of other compounds. 28: 19F NMR (282 MHz, 8, CDCI3): -163.6 (m, Freer,), -158.2 (t, Fpara), -143.7 (m, Fortho); IH NMR (300 MHz, 8, CDC13): 5.4 (b. H3) *, 3.52 (s, 2H, PfCH2), 1.8-2.4 (m, 6H, H 2, H 5, H6) *, 1.6-1.7 (6H, Me 4, PfCH2C(Me)=)*. MS (El): m/z: 302 (M+). *: overlapped with signals of other compounds. 30: 19F NMR (282 MHz, 8, CDCI3): -160.7 (m. Fmem), -148.7 (tt, 3JF-F = 21 Hz, 4JF-F = 4.7 Hz, Fpar,), -138.5 (m, Fortho); IH NMR (300 MHz, 8, CDC13): 3.98 (s, COOMe). MS (El): m/z(relative intensity): 226 (M +, 5), 195 (41), 167 (44), 117 (100), 98 (34), 79 (23). HRMS calcd for C8H3F502, m/z 226.0053; found 226.0055. 31: 19F NMR (282 MHz, 8, CDCI3): -157.9 (m, F 3, F3'), -140.3 (m, F 2, H2'); IH NMR (300 MHz, 8, CDC13): 4.16 (t, 5JH.F = 2.0 Hz, 3H, OMe), 3.96 (s, 3H, COOMe). MS (El): m/z(relative intensity): 238 (M +, 19), 207 (100), 192 (11), 148 (14), 136 (46), 117 (78), 101 (34), 99 (17), 98 (26), 79 (16), 59 (14). HRMS calcd for C9H6F403, m/z 238.0253; found 238.0255. Carbonylation of a mixture of 20 and 7. The above procedure was employed but R-(+)-limonene and [Pd(C6F5)Br(NCMe)2] were reacted at 0 °C for 80 min. A mixture of 201 (14%), 202 (42%), 71 (32%) and 72 (7%) was
obtained as shown by 19F NMR. The final colorless oily residue after the carbonylation procedure was analyzed and it contained 141 (20%), 142 (4%), 25 (5%, mixture of diastereoisomers), 26 (40%), 29 (13%), 28 (4%) and 27 (2%). In addition, unidentified compounds (12% total, each one less than 4%) were found. The products were separated in two batches by column chromatography (silica gel) eluting with n-hexane first (26, 27, 28 and 29) and then diethyl ether (ester derivatives).
A. C. A lbdniz et al. / Tetrahedron 54 (1998) 13851-13866
13865
29: lgF NMR (282 MHz, 8, CDCI3): -163.5 (m, Fmeta),-158.5 (t, Fpara),-143.6 (m, Fortho); IH NMR (300 MHz, 13, CDC13): 5.7 (m, IH, H3), 5.55 (m, 1H, H4), 5.35 (m, 1H, HI), 2.75 (m, IH, PfCHH'), 2.5 (m, IH, PfCHH'), 1.9-1.3 (m, H 5, H 6, PfCH2CH(Me)-) 1.66 (s, 3H, Me2), 0.99 (d, J = 6.7 Hz, 3H, PfCH2CH(Me)-)*. MS (El): m/z: 302 (M+). *: overlapped with signals of other compounds.
Acknowledgments This work was supported by the Direcci6n General de Investigaci6n Cientffica y Tdcnica (Spain) (Project PB96-0363), the Commission of the European Communities (Network "Selective Processes and Catalysis Involving Small Molecules", CHRX-CT93-0147) and the Junta de Castilla y Le6n (Project VA 40-96). Y.-S. L. thanks the Spanish Ministerio de Educaci6n y Ciencia and the A.E.C.l./I.C.D.-Universidad de Valladolid for fellowships.
References [I] Harrington, P. J, in Comprehensive Organometallic Chemistt3": A Review vf the Literature 1982-1994, eds. Abel, E. W.; Stone, F. G. A.; Wilkinson, G. Pergamon Press, Oxford 1995, Vvl 12, Chap. 8.2. [21 Tsuji, J. Palladium Reagents and C~Jtalysis, Wiley: Chichester, 1995. [3] Hegedus, L. S. in Orgam,,etallics in ,~vnthesis (Ed.: M. Schlosser), Wiley, 1994, Chap. 5, [4] De Meijere, A.; IVleyer, F. E. Allgew. Chem. hit. Ed. Ellgl. 1994, 33, 2379. [5] Heck, R. F. Palladimn Reagents in Organic Syntheses; Academic Press: London, 1985. 16] Trost, B. M.; Verhoeven, T. R. in Comprehensive Organometallie Chemistt3", Vol. 8 (Eds.: Wilkinson, G.; Stone, F. G. A.; Abel, E. W.), Pergamon Press, Oxford, 1982, Chap. 57. [71 B/ickvall, J. -E. Adr. Met. Org. Chem. 1989, I. 135. [8] AIb6niz, A. C.; Espinet. P; l_in, Y. -S. Organometallics. 1997, /6, 4138-4144. [9] AIb6niz, A. C.; Espinet. P; l-in, Y. -S. Organometallics, 1995, 14. 2977-2986. [10] AIb6niz A. C.; Espinet, P. Organometallics. 1991, 10, 2987-2988. [ I I I Colquhoun, H. M.; Thompson, D. J.; Twigg, M. V. Carbom'lation: Direct Synthesis of Carbonyl Compounds , Plenum Press, N.Y., 1991. [I 2] Btickvall, J. E.; Nordberg, R. E.; Zettcrberg, K.: ,~kcrmark, B. Organometallics 1983, 2, 1625-1629. [13} Milstein, D. Organometallics 1982, /, 888-890. [14] Hines, l'. F.; Stille, J. K. J. Am. Chem. Soc. 1972, 485-490. [151 Stille, J. K.; Hines, L. F. J. Am. Chem. Soc. 1970, 1798-1799. [161 Ozawa, F.; Son, T.-I.; Osakada, K.; Yamamoto, A. J. Chem. Soc. Chem. Commun. 1989. 1067-1068.
13866
A. C. A lb~niz et al. / Tetrahedron 54 (1998) 1 3 8 5 1 - 1 3 8 6 6
[17] Tsuji, J.; Kiji. J.; Morikawa, M. Tetrahedron Lett. 1963. 26, 1811-18[3. [18] Tsuji. J.; lmamura, S.; Kiji, J. J. Am. Chem. Soc. 1964.86, 4491. [19] Long, R.: Whillield, G. H. J. Chem. Soc. 1964, 1852-1853. [20] Shimizu, 1.: Maruyama. T.: Makuta, T.: Yamamoto, A. Tetrahedron Left. 1993, 34 (13]. 2135-2i38. [21J Wang. S.-Z.; Yamamoto. K.: Yamada, H.: Takahashi, T. Tetrt~hedron 1992.48 (12), 2333-2348. [22]Tsuji. J.;Sato. K.;()kumoto, H.J, Org. Chem. 1984.49. 1341-1344. [23] Tsuji, J.: Hosaka, S. J. Am. Chem. Sot'. 1965. 4075-4079. [24] Brewis, S.; Hughes. P. R, J. Chem. Sot'. Chem. Commlm. 1965, 157-158. (25] Tsuji, J.; Kiji, J.; Imamura, S.: /vlorikawa. M. J. Am. Chem. Soc. 1964, 86, 4350-4353. [26] Hosokawa. T.: Maiflis, P. M. J. Am. Chem. Soc. 1973. 4924-4931. J27] Carluran. G.: Graziani. M.: Ros, R.; Belluco, U. J. Chem. Soc. Dalton Trans 1972, 262-265. [28] AIb,Sniz, A. C.: Espinel, P.: Foccs-Foces, C.: Cano, F. H. Orgamm~etallics 1990, 9, 1079-1085. [29] Alb,5.niz. A. C.; Espinet. P.: Jeannin, Y.; Philoche-Levisalles, M.: /Vlann. B. E. J. Am. Chem. Soc.. 1990, 112. 6594-6600. [30] March, J. Advalwed Orgatlic Chemistt T. Wiley: New York. 1992; p. 586. [3l] James. D. E..Stille. J. K.J. Am. Chem. Soc. 1976, 1810-1823.