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A modification of the Hiyama reaction. Synthesis of homo allylic amines from imines and allylic bromides in the presence of CrCl2
Tcuahedron Lenm. Vol. 34, No. 22, PP. 3635-3638.1993 Ritcd in Great Britain
00404039193 $6.00 + .OO Pqamml Press LLd
A Modification of the Hiyama Reaction. Synthesis of Homo Allylic Amines from lmines and Allylic Bromides in the Presence of CrCl2
Maria Giammaruco, Maurixio Taddei* and Paola Ulivi Dipartirnento di Chimica Organica “Ugo Schiff”, Universiti di Fiinxe, Via G. Capponi 9, I-50121 Fiinxe, Italy
Abstract: Arylic and alkylic imines, activated with BFj.OEt, react with digerent allylic bromides in the presence of CrClz to give the corresponding homo ally&c amines. The reaction can be performed in a single step stamkg from the aldehyde and the amine, in the presence of molecular sieves (4 A), in a sort of amino-allylation of aldehydes. With the imine derived from benzaldehyde and (S)-valine a good diastereomeric excess (86%) is obtained.
The Hiyama reaction’ between allylic bromides* and aldehydes in the presence of CrCl2 is an efficient and expeditious route to prepare homo allylic alcohols3. The stereochemistry of the reaction has been studied4 and recently it has been also applied to the ring closure of polyunsaturated macrocycles The reaction has been reported to be highly chemoselectivel so that the electrophilic partners of the allyl-CrfJII) reagents were always aldehydes or ketones. Following our interest in the synthesis of biologically active amino acids,6 we found that allylic bromides react with aldimines, previously activated with BF3. OEt;?, to give the cormsponding homo allylic amines in good yields.7 (Scheme 1) **pg l&H
H
BF3’0Et2 I THF I WI, +
eBr
R = Arylor alkyl; Pg = Protecting group
) R’L Scheme 1
In a typical reaction procedure (path A in Table 1) BF3. OEt2 (1 mmol) was added, under nitrogen, to a solution of the imine (1 mmol) in dry THF (3 mL) at room temperature. This clear yellow solution was added with a syringe to a flask containing 002 (2.5 mmol), under inert atmosphere. followed by the allylic bromide (1.2 mmol). After stirring at room temperature for 2-6 h (see Table), hydrolytic work-up with a 10 8 solution of Na2C03 and extiaction with ethyl ether, followed by column chromatography on silica gel, gave the desired amine with the yields reported in Table 1. Anhydrous CrC12 was used as purchased from Aldrich. The salt should be grey. The partially hydrated greenish grey salt gave unsuccessful results, as, for example, transformation of the imines into aldehydes and, occasionally, further allylation of the so formed aldehyde to give the homo allylic alcohol. Drying this salt
3636
Table 1. Reactiin of altyl-Cr(lll) reagents with imines. Aftyl halides
lmines
5r-W
N/
H _ N _ p-CsH40~
PW,O~
cf
YieldSa
Products
Reac. conditbns
I
‘,I
H
Br
@
\ pathA
65%
1 h. 0?
2
1
2
H,N-+sH401111e
-Cl
1
pathAb 3h.
52%O
4
3
1
MeOOC-Br
pathA
3 h.
pathA
6h.
Br 1 6
H.
2
pathA
1h
N
_
CH&,H,
d”
67% 11
H .N.
N c PGH40~
PG++40~
I
6
A
2
H
path B
1h
&
45%
12
13 2
path B
2h
L
t
14 Nx
‘N x
COOMe 2
6
15
path5
COOMe
4h. +
I
17
’
750/f
16 a) Yields of isolated and fully characterized products. b) Reactioncarried out in the presence of 5 eq. of dry Nat c) Chtained as a mixture of dlastereoisomers 1 : 1 . d) Obtained as a mixture of diastereoisomsrs 1.5 : 1. e) Cbatined as a mixture of diastereoisomers 5 : 1 . 1) Isolated with a d.e. = 66% (NMR analysis)
3637
heating with the flame the reaction flask under vacuum, before the reaction, avoided the previous mentioned troubles but gave low yields of amines. The reaction was compatible with the most common protecting groups of the nitrogen (e.g. benzyl, and p-methoxyphenyl) and also a functional&d allylic bromide was employed. The experimental procedure can be modified to perform a direct amino-allylation of ahlehydes in a single pot reaction. (Scheme 2) 1) 2)
Molecularsieves ti I THF e
Br BFs’OEt2 I CrCl2
R’NH2
Scheme 2 In this modified procedure (path B in Table 1) the aldehyde (1 mmol) and the amine (1.2 mmol) were mixed in THF (3 mL) in the presence of molecular sieves (4A). After stirring for l-3 h at room temperature, the gas chromatographic analysis of the mixture showed the disappearance of the aldehyde peak and the formation of the peak of the imine at a higher retention time.s To this solution, BFs.OEb (1 mmol) was added and following the procedure described above, we obtained the corresponding homo allylic amine in good overall yields. This procedure was successfully applied to several aldehydes / imines (see Table 1) and proved to be useful because it prevented the isolation of the imine which can be troublesome especially working on small scale. Several observations on the regiochemistry and the stereochemistry of the products obtained suggested a different behavior in respect to the Hiyama reaction with aldehydes. The reaction did not work in the absence of BFsOEtz9 and the use of substituted allylic bromides gave different products depending on the hindrance and on the electronic effects of the substituents on the bromide (see entries 2,3 and 4 in Table l).‘O Moreover in the reaction of crotyl-CrfJII) (entry 2). the typical high rhreo selectivity of the Hiyama reaction with aldehydest’ was not observed. From these data we believe that the reaction can be probably described by a Cram type model (see entry 7 in Table 1) of alicyclic approach of the allyl-Cr(III) to the complex imine-BFs where the chromium is not able to coordinate the nitrogen aheady engaged with the BFs. The high stereoselectivity obtained in the reaction with the imine derived from (S)-valine (entry 8 in Table 1) points out that the chromium still acts as a chelating Lewis acid in the presence of oxygenated functions and suggest a possible analogy in the reactivity of our allyl-cr(III) / BFs.OEb reagent with high order cuprate~.~* Despite the low stereoselectivity of the crotyl-type derivatives, we believe that this methodology can be useful in the synthesis of unsaturated amines because the procedure is very simple and the level of compatibility with different functional groups on the two parts of the molecule linked by the new C-C bond formation is high. Applications of this reaction to the synthesis of biologically active amines and studies to improve the possibility to prepare optically active compounds are in progress and will be reported in due course.
Acknowledgments. This work was financially supported by Minister0 della Ricerca Scientifica e Tecnologica(Rome) Fondi MURST-4096.
Referencesand Notes. 1.
2. 3. 4. 5. 6. 7.
8.
9. 10.
11. 12.
Ok&, Y.; Hirano. S.; Hiyama, T; H. Nor&i J. Am. Chem. Sot. 1977,99,3179.Hiyama, T.; Kimura. K.; Nozaki, H. TetrahedronMt. 1981.22,1037. Hiyama, T.; Gkude, Y.; Kimura. K.; Nozaki, H. Bull. Chem. Sot. Jpn. l982,55,561. The reaction was also reported with allylic tosylates and allylic phosphonates. Jubert, C.; Nowotny, S.; Komemann, D.; Antes, I.; Tucker, C.E.; Knochel, P. J. Org. Chem. 1992.57.6384. For a review see: Saccomano. N.A.; in Comprehensive Organic Synthesis,Trost, B.M. Ed.; Pergamon Press, Gxford, 1991, p 173. Mulzer, J.; Kattner, L.; Strecker, A.R.; Schroder, C.; Buschmann, J.; Lehmann, C.; Luger, P. J. Am. Chem. Sot. 1991,113,4218. Wender, P.A.; Wisniwski, J.; Hoffmann, U.; Mah, R. TetrahedronI.&t, l!WO,31,6605. Paquette, L.A.; Astles, P.C. J. Org. Chem. 1993,53,165. For the allylation reaction of amino aklehydes see: D’Aniello, F.; Gehanne, S.; Taddei, M. Tetrahedron Lett. W&33,5621. D’Aniello, F.; Taddei, M. J. Org. Chem. 1992,52,5247. Variuos allylic organometallics have also been used in additions to imines: Yamamoto, Y.; Komatsu. T.; Maruyama. K. J. Am. Chem. Sot. 1984,106.5031.Keck. G.E.; Enholm, E.J. J. Org. Chem. 1985, SO, 147. Yamamoto, Y.; Komatsu, T.; Maruyama, K. J. Org. Chem. 1985.50, 3115. Wuts, P.G.M.; Jung, Y.W. Tetruhedron ht. D&$27,2079. Yamamoto,Y.; Nishii, S.; Maruyama, K.; Komatsu, T.; Ito, W. J. Am. Chem. Sot. 1986.108. 7778. Boga, C.; Savoia, D.; Umani-Ronchi, A. Tetrahedron: Asymmetry1990,I, 291. Sisko, J.; Weinreb. S.M. J. Org. Gem. 19%,X5, 393.Tanaka, H.; Inoue, K.; Pokomki, U.; Taniguchi. M.; Torii, S. TetrahedronWt.. l!WO,31,3023. Kobayashi. Y.; Nakatani. K.; Ito, Y.; Terashima, S. Chem. L&t. 19%,1709. Wuts, P.G.M.; Jung, Y.W. J. Org. Chem. l!B1,56,365. Laschat, S.; Kunz, H. J. Org. Chem. 1991,56,5883.Itsuno, S.; Yanaka, H.; Hachisuka, C.; Ito, K. J. Gem. Sot. Perkin Trans. I 1991,1341.Higashiyama, Ic; Inoue. H.; Takahashi, H. Tetrahedron L&t. 1992,33,235.Dembele, Y.A.; Belaud, C.; Villicras, J. Tetrahedron: Asymmetry1992,3,511. Beuchet, P.; Le Marrec, N.; Mosset, P. TetrahedronL&t. lW2,33,5959 For the preparation of aldimines see: Layer, R.W. Chem. Rev. 1%3. 63. 489. For the catalysis by molecular sieves in the preparation of imines see: Taguchi, K.; Westheimer, F.H. J. Org. Gem. 1971, 36, 1570. The reaction carried out without BFsGEt2 gave only 3-5% of the desired amines together with by
products coming from acidic decomposition of the imines. The reaction of benzaldehyde with allylic bromides 6 and 8 in the presence of CtClz was never reported, to our knowledge. We performed this reaction obtainig the pmducts arising from addition of the allylic-Cr(III) reagents to the carbonyl exclusively with allylic shift. For three selective reaction of aldehydes and crotyl bromides in the presence of CrCl~ see: Buse, C.T.; Heathcock, C.H. TetruhedronL.&t.1978,19,1685. Bococum, A.; Boga, C.; Savoia, D.; Umani-Ronchi, A. TetrahedronL&t. 1991.32,1367.
(Received in UK 14 April 1993)
00404039193 $6.00 + .OO Pqamml Press LLd
A Modification of the Hiyama Reaction. Synthesis of Homo Allylic Amines from lmines and Allylic Bromides in the Presence of CrCl2
Maria Giammaruco, Maurixio Taddei* and Paola Ulivi Dipartirnento di Chimica Organica “Ugo Schiff”, Universiti di Fiinxe, Via G. Capponi 9, I-50121 Fiinxe, Italy
Abstract: Arylic and alkylic imines, activated with BFj.OEt, react with digerent allylic bromides in the presence of CrClz to give the corresponding homo ally&c amines. The reaction can be performed in a single step stamkg from the aldehyde and the amine, in the presence of molecular sieves (4 A), in a sort of amino-allylation of aldehydes. With the imine derived from benzaldehyde and (S)-valine a good diastereomeric excess (86%) is obtained.
The Hiyama reaction’ between allylic bromides* and aldehydes in the presence of CrCl2 is an efficient and expeditious route to prepare homo allylic alcohols3. The stereochemistry of the reaction has been studied4 and recently it has been also applied to the ring closure of polyunsaturated macrocycles The reaction has been reported to be highly chemoselectivel so that the electrophilic partners of the allyl-CrfJII) reagents were always aldehydes or ketones. Following our interest in the synthesis of biologically active amino acids,6 we found that allylic bromides react with aldimines, previously activated with BF3. OEt;?, to give the cormsponding homo allylic amines in good yields.7 (Scheme 1) **pg l&H
H
BF3’0Et2 I THF I WI, +
eBr
R = Arylor alkyl; Pg = Protecting group
) R’L Scheme 1
In a typical reaction procedure (path A in Table 1) BF3. OEt2 (1 mmol) was added, under nitrogen, to a solution of the imine (1 mmol) in dry THF (3 mL) at room temperature. This clear yellow solution was added with a syringe to a flask containing 002 (2.5 mmol), under inert atmosphere. followed by the allylic bromide (1.2 mmol). After stirring at room temperature for 2-6 h (see Table), hydrolytic work-up with a 10 8 solution of Na2C03 and extiaction with ethyl ether, followed by column chromatography on silica gel, gave the desired amine with the yields reported in Table 1. Anhydrous CrC12 was used as purchased from Aldrich. The salt should be grey. The partially hydrated greenish grey salt gave unsuccessful results, as, for example, transformation of the imines into aldehydes and, occasionally, further allylation of the so formed aldehyde to give the homo allylic alcohol. Drying this salt
3636
Table 1. Reactiin of altyl-Cr(lll) reagents with imines. Aftyl halides
lmines
5r-W
N/
H _ N _ p-CsH40~
PW,O~
cf
YieldSa
Products
Reac. conditbns
I
‘,I
H
Br
@
\ pathA
65%
1 h. 0?
2
1
2
H,N-+sH401111e
-Cl
1
pathAb 3h.
52%O
4
3
1
MeOOC-Br
pathA
3 h.
pathA
6h.
Br 1 6
H.
2
pathA
1h
N
_
CH&,H,
d”
67% 11
H .N.
N c PGH40~
PG++40~
I
6
A
2
H
path B
1h
&
45%
12
13 2
path B
2h
L
t
14 Nx
‘N x
COOMe 2
6
15
path5
COOMe
4h. +
I
17
’
750/f
16 a) Yields of isolated and fully characterized products. b) Reactioncarried out in the presence of 5 eq. of dry Nat c) Chtained as a mixture of dlastereoisomers 1 : 1 . d) Obtained as a mixture of diastereoisomsrs 1.5 : 1. e) Cbatined as a mixture of diastereoisomers 5 : 1 . 1) Isolated with a d.e. = 66% (NMR analysis)
3637
heating with the flame the reaction flask under vacuum, before the reaction, avoided the previous mentioned troubles but gave low yields of amines. The reaction was compatible with the most common protecting groups of the nitrogen (e.g. benzyl, and p-methoxyphenyl) and also a functional&d allylic bromide was employed. The experimental procedure can be modified to perform a direct amino-allylation of ahlehydes in a single pot reaction. (Scheme 2) 1) 2)
Molecularsieves ti I THF e
Br BFs’OEt2 I CrCl2
R’NH2
Scheme 2 In this modified procedure (path B in Table 1) the aldehyde (1 mmol) and the amine (1.2 mmol) were mixed in THF (3 mL) in the presence of molecular sieves (4A). After stirring for l-3 h at room temperature, the gas chromatographic analysis of the mixture showed the disappearance of the aldehyde peak and the formation of the peak of the imine at a higher retention time.s To this solution, BFs.OEb (1 mmol) was added and following the procedure described above, we obtained the corresponding homo allylic amine in good overall yields. This procedure was successfully applied to several aldehydes / imines (see Table 1) and proved to be useful because it prevented the isolation of the imine which can be troublesome especially working on small scale. Several observations on the regiochemistry and the stereochemistry of the products obtained suggested a different behavior in respect to the Hiyama reaction with aldehydes. The reaction did not work in the absence of BFsOEtz9 and the use of substituted allylic bromides gave different products depending on the hindrance and on the electronic effects of the substituents on the bromide (see entries 2,3 and 4 in Table l).‘O Moreover in the reaction of crotyl-CrfJII) (entry 2). the typical high rhreo selectivity of the Hiyama reaction with aldehydest’ was not observed. From these data we believe that the reaction can be probably described by a Cram type model (see entry 7 in Table 1) of alicyclic approach of the allyl-Cr(III) to the complex imine-BFs where the chromium is not able to coordinate the nitrogen aheady engaged with the BFs. The high stereoselectivity obtained in the reaction with the imine derived from (S)-valine (entry 8 in Table 1) points out that the chromium still acts as a chelating Lewis acid in the presence of oxygenated functions and suggest a possible analogy in the reactivity of our allyl-cr(III) / BFs.OEb reagent with high order cuprate~.~* Despite the low stereoselectivity of the crotyl-type derivatives, we believe that this methodology can be useful in the synthesis of unsaturated amines because the procedure is very simple and the level of compatibility with different functional groups on the two parts of the molecule linked by the new C-C bond formation is high. Applications of this reaction to the synthesis of biologically active amines and studies to improve the possibility to prepare optically active compounds are in progress and will be reported in due course.
Acknowledgments. This work was financially supported by Minister0 della Ricerca Scientifica e Tecnologica(Rome) Fondi MURST-4096.
Referencesand Notes. 1.
2. 3. 4. 5. 6. 7.
8.
9. 10.
11. 12.
Ok&, Y.; Hirano. S.; Hiyama, T; H. Nor&i J. Am. Chem. Sot. 1977,99,3179.Hiyama, T.; Kimura. K.; Nozaki, H. TetrahedronMt. 1981.22,1037. Hiyama, T.; Gkude, Y.; Kimura. K.; Nozaki, H. Bull. Chem. Sot. Jpn. l982,55,561. The reaction was also reported with allylic tosylates and allylic phosphonates. Jubert, C.; Nowotny, S.; Komemann, D.; Antes, I.; Tucker, C.E.; Knochel, P. J. Org. Chem. 1992.57.6384. For a review see: Saccomano. N.A.; in Comprehensive Organic Synthesis,Trost, B.M. Ed.; Pergamon Press, Gxford, 1991, p 173. Mulzer, J.; Kattner, L.; Strecker, A.R.; Schroder, C.; Buschmann, J.; Lehmann, C.; Luger, P. J. Am. Chem. Sot. 1991,113,4218. Wender, P.A.; Wisniwski, J.; Hoffmann, U.; Mah, R. TetrahedronI.&t, l!WO,31,6605. Paquette, L.A.; Astles, P.C. J. Org. Chem. 1993,53,165. For the allylation reaction of amino aklehydes see: D’Aniello, F.; Gehanne, S.; Taddei, M. Tetrahedron Lett. W&33,5621. D’Aniello, F.; Taddei, M. J. Org. Chem. 1992,52,5247. Variuos allylic organometallics have also been used in additions to imines: Yamamoto, Y.; Komatsu. T.; Maruyama. K. J. Am. Chem. Sot. 1984,106.5031.Keck. G.E.; Enholm, E.J. J. Org. Chem. 1985, SO, 147. Yamamoto, Y.; Komatsu, T.; Maruyama, K. J. Org. Chem. 1985.50, 3115. Wuts, P.G.M.; Jung, Y.W. Tetruhedron ht. D&$27,2079. Yamamoto,Y.; Nishii, S.; Maruyama, K.; Komatsu, T.; Ito, W. J. Am. Chem. Sot. 1986.108. 7778. Boga, C.; Savoia, D.; Umani-Ronchi, A. Tetrahedron: Asymmetry1990,I, 291. Sisko, J.; Weinreb. S.M. J. Org. Gem. 19%,X5, 393.Tanaka, H.; Inoue, K.; Pokomki, U.; Taniguchi. M.; Torii, S. TetrahedronWt.. l!WO,31,3023. Kobayashi. Y.; Nakatani. K.; Ito, Y.; Terashima, S. Chem. L&t. 19%,1709. Wuts, P.G.M.; Jung, Y.W. J. Org. Chem. l!B1,56,365. Laschat, S.; Kunz, H. J. Org. Chem. 1991,56,5883.Itsuno, S.; Yanaka, H.; Hachisuka, C.; Ito, K. J. Gem. Sot. Perkin Trans. I 1991,1341.Higashiyama, Ic; Inoue. H.; Takahashi, H. Tetrahedron L&t. 1992,33,235.Dembele, Y.A.; Belaud, C.; Villicras, J. Tetrahedron: Asymmetry1992,3,511. Beuchet, P.; Le Marrec, N.; Mosset, P. TetrahedronL&t. lW2,33,5959 For the preparation of aldimines see: Layer, R.W. Chem. Rev. 1%3. 63. 489. For the catalysis by molecular sieves in the preparation of imines see: Taguchi, K.; Westheimer, F.H. J. Org. Gem. 1971, 36, 1570. The reaction carried out without BFsGEt2 gave only 3-5% of the desired amines together with by
products coming from acidic decomposition of the imines. The reaction of benzaldehyde with allylic bromides 6 and 8 in the presence of CtClz was never reported, to our knowledge. We performed this reaction obtainig the pmducts arising from addition of the allylic-Cr(III) reagents to the carbonyl exclusively with allylic shift. For three selective reaction of aldehydes and crotyl bromides in the presence of CrCl~ see: Buse, C.T.; Heathcock, C.H. TetruhedronL.&t.1978,19,1685. Bococum, A.; Boga, C.; Savoia, D.; Umani-Ronchi, A. TetrahedronL&t. 1991.32,1367.
(Received in UK 14 April 1993)