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Regioselective functionalization of chiral nickelacycles derived from N-protected aspartic and glutamic anhydrides
cu404039/90 53.00 + .oo rcrgRess plc
Tet&x&on Letters.Vol.31. N0.33.pp 478347861990 Rikd in GreatBritain
REGIOSELECTIVE FUNCTIONALIZATION OF CHIRAL NICKELACYCLES DERIVED FROM N-PROTECTED ASPARTIC AND GLUTAMIC ANHYDRIDES’ Ana M. Castatio and Antonio
M. Echavarren’
Iostituto de Qufmica Orgtica,
CSIC,
Juan de la Cierva 3, 28006 Madrid Spain.
Summaly: The electrophilic cleavage of the nickelacycles resulting from oxidative addition of Ni(0) complexes to iv-protected
aspartic and glutamic anhydrides, followed by decarbonylation, gives rise regioselcctively to derivatives ofa-and Balaoine or a and 7 -aminobutyric acid, respectively.
The developing attracted
considerable
of synthetic strategies
for the preparation
of enantiomerically
interest in recent years.’ Much of the attention
although the use of alanine equivalents, and related synthons, has considerable the preparation important
pure amino acids has
has been focused on glycine synthons, synthetic potential.* In this regard,
of chiral nickelacycles 1 and 2 would provide valuable starting materials for the elaboration
of
natural and unnatural ammo acids.‘”
NIL, ‘0
Z
l,Z=NR,
i;(
3,Z=
NIL,
2,z=NFL,
b
H
4,Z=
Z Icr
0
H
0
Herein, we wish to report on the regioselective starting from readily available N-protected
generation
It is hoped that these nickelacycles will be of synthetic use as synthons for a-alanine Recently it was reported
that Ni(COD)(bpy)’
addition product, which after decarbonylation glutaric anhydride into the six-membered
1 and 2 (n = 1 or 2)
of oxanickelacycles
aspartic and glutamic acid anhydrides, and their electrophilic cleavage. and a-aminobutyric
reacts with succinic anhydride
affords nickelacycle 3.” A related reaction sequence transforms
ring nickelacycle 4, which can suffer isomerixation
ring complex by a R-hydride elimination/insertion
acid,
to give the oxidative to a five-membered
process.’
The utilization of aspartic or glutamic anhydrides* in the above reaction addresses the question of the regiochemical
control in the oxidative addition step to the unsymmetrical
anhydrides,
and the compatibility
of
the highly reactive Ni(0) complexes with the NH functionality and the protective groups. In the event, treatment of Cbz-aspartic
anhydride
with the complex Ni(COD)(bpy)
oxidative addition products.
in THF at 23 “C gave a dark red suspension
Hydrolysis with aq HCI gives the expected
Cbz-Asp-OH.
achieved after heating in THF for several hours, yielding a 1:l mixture of Cbz-a-Ala-OH
’ This Letter is dedicated to the memory of Prof. John K Stille.
4783
Decarbonylation
of was
and Cbx-B-Ala-OH in
4784
88 % yield: after acid quenching of the crude reaction decarbonylation
process are summarized
mixture. ” Selected results of this oxidative addition-
in Table 1.
Table 1. Oxidarive aaWtion and Decatiwnylation of N-ProtectedAsptiic Anh_witides.
+
COOH
THF. A:
Ni(COD&
+
H,O’
COOH
%N
a-Ala entry
1
R,RLb
Cbz,H
5
6
TFA,H
7
1
88
1
61
1
60
PCY,
1
1
18
dppf
1
3
54
TMEDA
Pht
(%a)
1
Me,Phen TMEDA
4
yieldb
2 9
bpy
2 3
B&a
product ratio a-Ala S-Ala
r,
QJ
bpy
2
1
86
1
3
91
8
Me,Phen
11
1
91
9
TMEDA
1
1
82
1
10
82
1
28
91d
4
1
80
10
PCY,
11 12
PPh;
(a) Unless otherwise stated, the reactions were carried out in THF under retlux for 4-8 h with 1.1-1.5 equiv of Ni(0) complex, prepared in situ from Ni(COD), and 1 equiv of the corresponding &and (except for entry 12, where 2 equiv were used). (b) Yields were determined by 300 MHz ’ H NMR, and were confirmed in several instances by isolation of the ammo acids or the methyl esters derivatives (CH,N,, Et,O). The only other constituent of the crude reaction mixture was the N-protected aspartic acid. (c) Reaction run at 23’C. (d) Reaction in benzene at 23’C for 25 h. Selective
C-4 attack by the Ni(0) complex was obtained
(entries 2,3, and 8), although replacement
of the iv-protecting
by using more sterically demanding
group by the more electron-withdrawing
ligands TPA or
Pht increases the amount of C-l attack (compare entries 3,6, and 9)” Particularly interesting was the observation that addition
of PC&, presumably
giving the coordinatively
reaction to c-1, leading, after decarbonylation
unsaturated
with the selective C-4 attack observed with PPh, (2 equiv) (entry coordination
of the unsaturated
complex Ni(COD)PCy,
and acid hydrolysis, to Pht-g-Ala-OH.*
12)” and may be a consequence
Ni(0) complex with the imide protective
benzene as solvent results in an increase of the regioselectivity
directs the
This result is in contrast
group. Accordingly,
of the
utilization
of
for oxidative addition through the C-l carbonyl.
On the other hand, no reaction was observed with Ni(COD), itself, or when Me,bpy or bqy were used as ligands. The reaction of (I?)-?viTPA-(S)-aspartic
anhydride” with Ni(0) to give (R)-MTPA-@)-Ala-OH
briefly examined to determine the degree of C-2 epimerization were obtained with PCy, and PPh, (80-90% de, determined de, and Me*Phen led to a 1:l mixture of diastereoisomers.”
was also
during the reaction sequence. Satisfactory results by ‘H and ‘F NMR), while TMEDA gave ca. 50%
4785
The oxidative addition of Ni(O), with concomitant
decarbonylation,
to N-protected
glutamic anhydrides
was also studied (Table 2). In this instance good to excellent selectivity in the oxidative addition through the C5 carbonyl was obtained for Cbz-glutamic anhydride. This trend was reversed again with PC& and the phthalimido protective
group, yielding Pht-y-Abu-OH
as the major product (Table 2, entry 6).
Table 2. &dative Addition and Decarbonylalion of N-Protected Glutantic Anhydtides.*
+ Q X0
THF,
Ni(COD)L,
R*N
A:
)
H,O’
0
WAbu
Clu
entry
R,R&
product ratio a:-Abu 7 -Abu
Cbz,H
1
bpy
2
Me,Phen
3
TMEDA
4
PC%
5
-Abu
Pht
6
yieldb (S)
5
1
75
4
1
6.5
250
96
>50
40
bpy
3
1
46
PCY,
1
3
91
(a) The reactions were carried out as in Table 1, but for 2-2.5 h. (b) See comment b in Table 1. Additionally small amounts (cu. 4-10 %) of Cbz-pyroglutamic acid were also obtained in several runs. Having established the regiochemical control in the oxidative addition step, the deuteriation membered
ring nickelacycles was also studied. Reaction of the decarbonylated
solution) at 23 “C gave 3-d-alanines
by using Ni(COD)(bpy)
metalacycles with DC1 (20% D,O
5 (as in entry 3, Table 1 but at 23 “C, 43% yield, 93% d) and mc-6 (entry
8, Table 1, 23 “C, 70-80% yield, 80-84 % d) (Eq l).” The corresponding prepared
mc-Pht3-d-g-Ala-OH
(7)” was also
(entry 7, Table I,23 “C, 38 % yield, 91 % d) .I6These results demonstrate
usefulness of the described reaction sequence for the selective labeling of alanines by decarboxylation acidsn
Furthermore,
treatment
of the five-
of mc-Pht-aspartic
followed by addition of N-bromosuccinimide
anhydride
with Ni(COD)(Me,Phen)
at 23 “C gave mc-Pht-3-bromo-Ala-OH
the
of aspartic
(Table 1, entry 8),
(8)” in 80 % yield (Eq I).”
0 +
COO”
THF; Ni(COD)L,
E’
E 0% 1) 5, 6, 8,
Further experiments
E-D. R-Cbr.H E = D, R = Pht E - Br. R - Pht
directed towards the determination
7, E - D. R = Pbl
of the synthetic potential of these and related
nickelacycles are in progress. Acknowledgment: Financial support of thii work by the DGICYT (PB87-0201-C-0~-02) and the Comunidad Aut6noma de Madrid (fellowship to A. M. C.) is gratefully acknowledged. We arc also grateful to Prof. M. Martin-Lomas for encouragement and support and Dr. P. Noheda for helpful discussions.
4786
Referencea and Notes 1. For a recent review, see: WiUiams, R. M. Synthesis of OpticallyActive a-Amino Acids, Pergamon: Ozford, 1989. 2. For recent developments, see: (a) Nucleophilic alanine equivalents: Baldwin, J. E.; Moloney, M. G.; North, M.J. Chem. Sot., Perhin Trans. I 1989,833, Tetrahedron 1989,4&W 6319. Jackson, R. F. W.; Wythes, M. J.; Wood, A. Tetrahedron L&t. 1989, 30,594l. Jackson, R. F. W.; James, K.; Wythcs, M. J.; Wood, A. J. Chem. Sot., Chem. Commun. 1989,644. Hegedus, L. S.; Schwindt, M. A.; De Lombaert, S.; Imwinkehied, R. 1. Am. Chem. Sot. 1990,112,2264. (b) Nucleophitic d’-aminobutytic acid equivalentsandt&.ted synthons: El Ma&ii A.; Roumestant. M.-L.; Pappalardo, L.; Viallefont, P. Bull. Sot. Chim. Fr. 1989,554. Attwood, M. R.; Carr, M. G.; Jordan, S. Tetrahedron Lett. 1990,31,283. (c) Elecbophilic aianine equivalents: Pansare, S. V.; Vcderas, J. C. J. Org. Chem. 1989,54,2311. Sato, I1, Kozikowski, A. P. TetmheaVonLett. 1989,30,4073. (d) For the palladiumcatalyzed reaction of an electrophihc aspartic acid synthon, see: Sahturo, F. G.; McDonald, I. A. J. Org. Chem. 1988,54,6l38. 3. Wagner, I.; Musso, H. Angou. Chem. Int. Ed En9 1983,22,816. 4. A recent report stresses the synthetic utility of a stmcinic acid derived nickelacycie as a propionic acid equivalent: Schiinecker, B.; Wahher, D.; Fischer, R.; Nestler, B.; Bdunlich, G.; Eibisch, H.; Droescher, P. Tetrahedron Lett. 1990,31, 1257. 5. Abbreviations: (Qandr) COD = 1,5-cyclooctadiene; bpy = 2,2’-bipyridme; Me,bpy = 4,4’-diiethyl-2,2’-bipyridine; Me,Phen = 2,9-dimethyl-l,lO-phenanthroiine; bqy = 2,2’-biquinohne; PCy r = tricyclohexylphosphine; TMEDA = N,N,N’,N’tetramethylethylenediamine; dppf = l,l’-bis(diphenylphosphino)ferrocene. (N-protectivegroups) Cbz = benzyloxycarbonyl; TFA = trifhtoroacctyl; Pht = phthaloyl; MTPA = a -methozy-a -trifluoromethylphenylacetyl. (Amino acids) Asp = aspartic; Glu = ghttamic; Ala = alanine; Abu = aminobutyric. 6. Uhhg, V. E.; Fehske, G.; Nestler, B. 2. Anorg. A& Chem. 1980,465, 141. 7. (a) Sane, K.; Yamamoto, T.; Yamamoto, A.; Bull. Chem. Sot. Jpn. 1984,57,2741. (b) Sano, K.; Yamamoto, T.; Yamamoto, A. Chem Lett. 1984, 941. (c) Sane, Ic, Yamamoto, T.; Yamamoto, A. Chem. Left. 1983, 115. (d) Yamamoto, T.; Sano, L, Yamamoto, A. J. Am. Chem. Sot. 1987,109,10!32. (d) See also: Grunewald, G. L.; Davis, D. P. 1. Org. Chem. 1978,43,3074 and references cited therein. 8. (a) Preparation of protected amino acids: Wtincb, E.; Ed. “hfethoden der Organ&hen Chemie. Houben-Weyt”, VoIs. 15/l and 15/2, G. Thieme: Stuttgart, 1972. (b) Cbz and TFA derivatives are optically pure compounds. Pitt derivatives are racemic. 9. Determined by ‘H NMR after hydrolysis of the decarbonylated products. The resulting amino acids were characterized by ‘H and “C NMR and by comparison with authentic samples. 10. The air sensitive nickelacycles are insoluble in NMR solvents. 11. (a) A moderate (ca. 1.41) selectivity for nucleophitica-attack (C-l) by methanol was reported for 5: see ref. 8a (Vol. 15/l, p. 322). (b) For the regioselective reduction of 5 with NaBH,, see: McGarvey, G. J.; Hiner, R. N.; Matsubara, Y.; Oh, T. Tetrahedron Left. 1983,24,2733. 12. A similar result was obtained with Ni(PPh,),, prepared in situ by reduction of NiCI,(PPh,), with Zn-Cu in the presence of 2 equiv of PPb: Sugimoto, T.; Misaki, Y.; Kajita, T.; Yoshida, Z.; Kai, Y.; Kasai, N. I. Am. them. Sot. 1987,109,4106. 13. Prepared in quantitative yield by dehydration (DCC or Ac,O) of optically pure (R)-MTPA-(S)-aspartic acid, synthetized by acylation of (S)-aspartic acid bis(trimethyIsily1) ester. Details of this procedure will be published shortly. 14. It is not clear at this moment if thii result is a consequence of a base catalyzed epimerization (see: Buckingham, D. A.; Stewart, I.; Sutton, P. A. I. Am. Chem. Sot. 1990, 112, S&5) or it takes place by means of a g-hydride elimination/insertion process.7 Experiments to ascertain this point are in progress. 15. These compounds have been fully characterized. NMR data for selected compounds: mc-6: ‘H NMR (300 MHz, DMSOd6) 6 7.95-7.80 (m, 4 H), 4.85 (t, J = 7.3 Hz, 1 H), 1.55 (br d, J = 7.2 Hz, 2 H); “C NMR (50 MHz, CDCI,) 6 176.1, 168.0, 134.2, 131.8, 123.5, 47.2, 14.7 (t, J = 20.1 Hz). mc-7:‘H NMR (300 Mz, DMSO-d,) 6 7.95-7.80 (m, 4 H), 3.77 (t, J = 7.3 Hz, lH), 2.59 (d, J = 7.3 Hz, 2 H); ‘“C NMR (50 MHz, CDCI,) 6 174.9, 167.4, 134.1, 131.9, 123.4, 33.2 (t, J = 22.4 Hz), 32.4. mc-8: ‘H NMR (300 Mz, DMSO-I,) 6 8.00-7.80 (m, 4 H), 5.18 (dd, J = 11.0, 5.0 Hz, 1 H), 4.11 (dd, J = 10.7, 5.0 Hz, 1 H), 4.03 (t, J = 10.8 Hz, 1 H); ‘“C NMR (50 MHz, CDCI,) 6 169.4, 167.2, 134.3, 131.6, 123.8, 53.4, 28.3. 16. (a) For the synthesis of deuteriateda-alanines, see: Gani, D.; Young, D. W. I. Cbem. Sot., Chem. Commun. 1983,576; J. Chem. Sot.. Perhin Tmns. 1 1985, 1355. Santaniello, E.; Manzocchi, A.; Biondii P. A. J. Chem. Sot., Perhin Tmns. I 1981,307. (b) For the enzymatic preparation of deuteriated alanines, see: Esaki, N.; Sawada, S.; Tanaka, H.; Soda, K. Anal. B&hem. 1982, 119,281. (c) For the photochemicaio-decarboxylation of benzoyl-Asp-OH, see: Nakai, H.; Sato, I.; Mizoguchi, T.; Kanaoka, Y. Synthesis 1982, 141. 17. The preparation ofa-alanine from aspartic acid mimics the action of the enzyme aspartic acid g-decarboxylasc. For a leading reference, see: Chang, C.-C.; Laghai, A.; O’Lcarly, M. H.; Floss, H. G. I: Biol. C’hem. 1982,257,3564. 18. For the synthesis of (S)-Cbz-3-bromoaianine from serine, see: Arnold, L. D.; KaIantar, T. H.; Vederas, J. C. J. Am. Chem. sot. 1985,107,7105.
(Received
in UK 22 June 1990)
Tet&x&on Letters.Vol.31. N0.33.pp 478347861990 Rikd in GreatBritain
REGIOSELECTIVE FUNCTIONALIZATION OF CHIRAL NICKELACYCLES DERIVED FROM N-PROTECTED ASPARTIC AND GLUTAMIC ANHYDRIDES’ Ana M. Castatio and Antonio
M. Echavarren’
Iostituto de Qufmica Orgtica,
CSIC,
Juan de la Cierva 3, 28006 Madrid Spain.
Summaly: The electrophilic cleavage of the nickelacycles resulting from oxidative addition of Ni(0) complexes to iv-protected
aspartic and glutamic anhydrides, followed by decarbonylation, gives rise regioselcctively to derivatives ofa-and Balaoine or a and 7 -aminobutyric acid, respectively.
The developing attracted
considerable
of synthetic strategies
for the preparation
of enantiomerically
interest in recent years.’ Much of the attention
although the use of alanine equivalents, and related synthons, has considerable the preparation important
pure amino acids has
has been focused on glycine synthons, synthetic potential.* In this regard,
of chiral nickelacycles 1 and 2 would provide valuable starting materials for the elaboration
of
natural and unnatural ammo acids.‘”
NIL, ‘0
Z
l,Z=NR,
i;(
3,Z=
NIL,
2,z=NFL,
b
H
4,Z=
Z Icr
0
H
0
Herein, we wish to report on the regioselective starting from readily available N-protected
generation
It is hoped that these nickelacycles will be of synthetic use as synthons for a-alanine Recently it was reported
that Ni(COD)(bpy)’
addition product, which after decarbonylation glutaric anhydride into the six-membered
1 and 2 (n = 1 or 2)
of oxanickelacycles
aspartic and glutamic acid anhydrides, and their electrophilic cleavage. and a-aminobutyric
reacts with succinic anhydride
affords nickelacycle 3.” A related reaction sequence transforms
ring nickelacycle 4, which can suffer isomerixation
ring complex by a R-hydride elimination/insertion
acid,
to give the oxidative to a five-membered
process.’
The utilization of aspartic or glutamic anhydrides* in the above reaction addresses the question of the regiochemical
control in the oxidative addition step to the unsymmetrical
anhydrides,
and the compatibility
of
the highly reactive Ni(0) complexes with the NH functionality and the protective groups. In the event, treatment of Cbz-aspartic
anhydride
with the complex Ni(COD)(bpy)
oxidative addition products.
in THF at 23 “C gave a dark red suspension
Hydrolysis with aq HCI gives the expected
Cbz-Asp-OH.
achieved after heating in THF for several hours, yielding a 1:l mixture of Cbz-a-Ala-OH
’ This Letter is dedicated to the memory of Prof. John K Stille.
4783
Decarbonylation
of was
and Cbx-B-Ala-OH in
4784
88 % yield: after acid quenching of the crude reaction decarbonylation
process are summarized
mixture. ” Selected results of this oxidative addition-
in Table 1.
Table 1. Oxidarive aaWtion and Decatiwnylation of N-ProtectedAsptiic Anh_witides.
+
COOH
THF. A:
Ni(COD&
+
H,O’
COOH
%N
a-Ala entry
1
R,RLb
Cbz,H
5
6
TFA,H
7
1
88
1
61
1
60
PCY,
1
1
18
dppf
1
3
54
TMEDA
Pht
(%a)
1
Me,Phen TMEDA
4
yieldb
2 9
bpy
2 3
B&a
product ratio a-Ala S-Ala
r,
QJ
bpy
2
1
86
1
3
91
8
Me,Phen
11
1
91
9
TMEDA
1
1
82
1
10
82
1
28
91d
4
1
80
10
PCY,
11 12
PPh;
(a) Unless otherwise stated, the reactions were carried out in THF under retlux for 4-8 h with 1.1-1.5 equiv of Ni(0) complex, prepared in situ from Ni(COD), and 1 equiv of the corresponding &and (except for entry 12, where 2 equiv were used). (b) Yields were determined by 300 MHz ’ H NMR, and were confirmed in several instances by isolation of the ammo acids or the methyl esters derivatives (CH,N,, Et,O). The only other constituent of the crude reaction mixture was the N-protected aspartic acid. (c) Reaction run at 23’C. (d) Reaction in benzene at 23’C for 25 h. Selective
C-4 attack by the Ni(0) complex was obtained
(entries 2,3, and 8), although replacement
of the iv-protecting
by using more sterically demanding
group by the more electron-withdrawing
ligands TPA or
Pht increases the amount of C-l attack (compare entries 3,6, and 9)” Particularly interesting was the observation that addition
of PC&, presumably
giving the coordinatively
reaction to c-1, leading, after decarbonylation
unsaturated
with the selective C-4 attack observed with PPh, (2 equiv) (entry coordination
of the unsaturated
complex Ni(COD)PCy,
and acid hydrolysis, to Pht-g-Ala-OH.*
12)” and may be a consequence
Ni(0) complex with the imide protective
benzene as solvent results in an increase of the regioselectivity
directs the
This result is in contrast
group. Accordingly,
of the
utilization
of
for oxidative addition through the C-l carbonyl.
On the other hand, no reaction was observed with Ni(COD), itself, or when Me,bpy or bqy were used as ligands. The reaction of (I?)-?viTPA-(S)-aspartic
anhydride” with Ni(0) to give (R)-MTPA-@)-Ala-OH
briefly examined to determine the degree of C-2 epimerization were obtained with PCy, and PPh, (80-90% de, determined de, and Me*Phen led to a 1:l mixture of diastereoisomers.”
was also
during the reaction sequence. Satisfactory results by ‘H and ‘F NMR), while TMEDA gave ca. 50%
4785
The oxidative addition of Ni(O), with concomitant
decarbonylation,
to N-protected
glutamic anhydrides
was also studied (Table 2). In this instance good to excellent selectivity in the oxidative addition through the C5 carbonyl was obtained for Cbz-glutamic anhydride. This trend was reversed again with PC& and the phthalimido protective
group, yielding Pht-y-Abu-OH
as the major product (Table 2, entry 6).
Table 2. &dative Addition and Decarbonylalion of N-Protected Glutantic Anhydtides.*
+ Q X0
THF,
Ni(COD)L,
R*N
A:
)
H,O’
0
WAbu
Clu
entry
R,R&
product ratio a:-Abu 7 -Abu
Cbz,H
1
bpy
2
Me,Phen
3
TMEDA
4
PC%
5
-Abu
Pht
6
yieldb (S)
5
1
75
4
1
6.5
250
96
>50
40
bpy
3
1
46
PCY,
1
3
91
(a) The reactions were carried out as in Table 1, but for 2-2.5 h. (b) See comment b in Table 1. Additionally small amounts (cu. 4-10 %) of Cbz-pyroglutamic acid were also obtained in several runs. Having established the regiochemical control in the oxidative addition step, the deuteriation membered
ring nickelacycles was also studied. Reaction of the decarbonylated
solution) at 23 “C gave 3-d-alanines
by using Ni(COD)(bpy)
metalacycles with DC1 (20% D,O
5 (as in entry 3, Table 1 but at 23 “C, 43% yield, 93% d) and mc-6 (entry
8, Table 1, 23 “C, 70-80% yield, 80-84 % d) (Eq l).” The corresponding prepared
mc-Pht3-d-g-Ala-OH
(7)” was also
(entry 7, Table I,23 “C, 38 % yield, 91 % d) .I6These results demonstrate
usefulness of the described reaction sequence for the selective labeling of alanines by decarboxylation acidsn
Furthermore,
treatment
of the five-
of mc-Pht-aspartic
followed by addition of N-bromosuccinimide
anhydride
with Ni(COD)(Me,Phen)
at 23 “C gave mc-Pht-3-bromo-Ala-OH
the
of aspartic
(Table 1, entry 8),
(8)” in 80 % yield (Eq I).”
0 +
COO”
THF; Ni(COD)L,
E’
E 0% 1) 5, 6, 8,
Further experiments
E-D. R-Cbr.H E = D, R = Pht E - Br. R - Pht
directed towards the determination
7, E - D. R = Pbl
of the synthetic potential of these and related
nickelacycles are in progress. Acknowledgment: Financial support of thii work by the DGICYT (PB87-0201-C-0~-02) and the Comunidad Aut6noma de Madrid (fellowship to A. M. C.) is gratefully acknowledged. We arc also grateful to Prof. M. Martin-Lomas for encouragement and support and Dr. P. Noheda for helpful discussions.
4786
Referencea and Notes 1. For a recent review, see: WiUiams, R. M. Synthesis of OpticallyActive a-Amino Acids, Pergamon: Ozford, 1989. 2. For recent developments, see: (a) Nucleophilic alanine equivalents: Baldwin, J. E.; Moloney, M. G.; North, M.J. Chem. Sot., Perhin Trans. I 1989,833, Tetrahedron 1989,4&W 6319. Jackson, R. F. W.; Wythes, M. J.; Wood, A. Tetrahedron L&t. 1989, 30,594l. Jackson, R. F. W.; James, K.; Wythcs, M. J.; Wood, A. J. Chem. Sot., Chem. Commun. 1989,644. Hegedus, L. S.; Schwindt, M. A.; De Lombaert, S.; Imwinkehied, R. 1. Am. Chem. Sot. 1990,112,2264. (b) Nucleophitic d’-aminobutytic acid equivalentsandt&.ted synthons: El Ma&ii A.; Roumestant. M.-L.; Pappalardo, L.; Viallefont, P. Bull. Sot. Chim. Fr. 1989,554. Attwood, M. R.; Carr, M. G.; Jordan, S. Tetrahedron Lett. 1990,31,283. (c) Elecbophilic aianine equivalents: Pansare, S. V.; Vcderas, J. C. J. Org. Chem. 1989,54,2311. Sato, I1, Kozikowski, A. P. TetmheaVonLett. 1989,30,4073. (d) For the palladiumcatalyzed reaction of an electrophihc aspartic acid synthon, see: Sahturo, F. G.; McDonald, I. A. J. Org. Chem. 1988,54,6l38. 3. Wagner, I.; Musso, H. Angou. Chem. Int. Ed En9 1983,22,816. 4. A recent report stresses the synthetic utility of a stmcinic acid derived nickelacycie as a propionic acid equivalent: Schiinecker, B.; Wahher, D.; Fischer, R.; Nestler, B.; Bdunlich, G.; Eibisch, H.; Droescher, P. Tetrahedron Lett. 1990,31, 1257. 5. Abbreviations: (Qandr) COD = 1,5-cyclooctadiene; bpy = 2,2’-bipyridme; Me,bpy = 4,4’-diiethyl-2,2’-bipyridine; Me,Phen = 2,9-dimethyl-l,lO-phenanthroiine; bqy = 2,2’-biquinohne; PCy r = tricyclohexylphosphine; TMEDA = N,N,N’,N’tetramethylethylenediamine; dppf = l,l’-bis(diphenylphosphino)ferrocene. (N-protectivegroups) Cbz = benzyloxycarbonyl; TFA = trifhtoroacctyl; Pht = phthaloyl; MTPA = a -methozy-a -trifluoromethylphenylacetyl. (Amino acids) Asp = aspartic; Glu = ghttamic; Ala = alanine; Abu = aminobutyric. 6. Uhhg, V. E.; Fehske, G.; Nestler, B. 2. Anorg. A& Chem. 1980,465, 141. 7. (a) Sane, K.; Yamamoto, T.; Yamamoto, A.; Bull. Chem. Sot. Jpn. 1984,57,2741. (b) Sano, K.; Yamamoto, T.; Yamamoto, A. Chem Lett. 1984, 941. (c) Sane, Ic, Yamamoto, T.; Yamamoto, A. Chem. Left. 1983, 115. (d) Yamamoto, T.; Sano, L, Yamamoto, A. J. Am. Chem. Sot. 1987,109,10!32. (d) See also: Grunewald, G. L.; Davis, D. P. 1. Org. Chem. 1978,43,3074 and references cited therein. 8. (a) Preparation of protected amino acids: Wtincb, E.; Ed. “hfethoden der Organ&hen Chemie. Houben-Weyt”, VoIs. 15/l and 15/2, G. Thieme: Stuttgart, 1972. (b) Cbz and TFA derivatives are optically pure compounds. Pitt derivatives are racemic. 9. Determined by ‘H NMR after hydrolysis of the decarbonylated products. The resulting amino acids were characterized by ‘H and “C NMR and by comparison with authentic samples. 10. The air sensitive nickelacycles are insoluble in NMR solvents. 11. (a) A moderate (ca. 1.41) selectivity for nucleophitica-attack (C-l) by methanol was reported for 5: see ref. 8a (Vol. 15/l, p. 322). (b) For the regioselective reduction of 5 with NaBH,, see: McGarvey, G. J.; Hiner, R. N.; Matsubara, Y.; Oh, T. Tetrahedron Left. 1983,24,2733. 12. A similar result was obtained with Ni(PPh,),, prepared in situ by reduction of NiCI,(PPh,), with Zn-Cu in the presence of 2 equiv of PPb: Sugimoto, T.; Misaki, Y.; Kajita, T.; Yoshida, Z.; Kai, Y.; Kasai, N. I. Am. them. Sot. 1987,109,4106. 13. Prepared in quantitative yield by dehydration (DCC or Ac,O) of optically pure (R)-MTPA-(S)-aspartic acid, synthetized by acylation of (S)-aspartic acid bis(trimethyIsily1) ester. Details of this procedure will be published shortly. 14. It is not clear at this moment if thii result is a consequence of a base catalyzed epimerization (see: Buckingham, D. A.; Stewart, I.; Sutton, P. A. I. Am. Chem. Sot. 1990, 112, S&5) or it takes place by means of a g-hydride elimination/insertion process.7 Experiments to ascertain this point are in progress. 15. These compounds have been fully characterized. NMR data for selected compounds: mc-6: ‘H NMR (300 MHz, DMSOd6) 6 7.95-7.80 (m, 4 H), 4.85 (t, J = 7.3 Hz, 1 H), 1.55 (br d, J = 7.2 Hz, 2 H); “C NMR (50 MHz, CDCI,) 6 176.1, 168.0, 134.2, 131.8, 123.5, 47.2, 14.7 (t, J = 20.1 Hz). mc-7:‘H NMR (300 Mz, DMSO-d,) 6 7.95-7.80 (m, 4 H), 3.77 (t, J = 7.3 Hz, lH), 2.59 (d, J = 7.3 Hz, 2 H); ‘“C NMR (50 MHz, CDCI,) 6 174.9, 167.4, 134.1, 131.9, 123.4, 33.2 (t, J = 22.4 Hz), 32.4. mc-8: ‘H NMR (300 Mz, DMSO-I,) 6 8.00-7.80 (m, 4 H), 5.18 (dd, J = 11.0, 5.0 Hz, 1 H), 4.11 (dd, J = 10.7, 5.0 Hz, 1 H), 4.03 (t, J = 10.8 Hz, 1 H); ‘“C NMR (50 MHz, CDCI,) 6 169.4, 167.2, 134.3, 131.6, 123.8, 53.4, 28.3. 16. (a) For the synthesis of deuteriateda-alanines, see: Gani, D.; Young, D. W. I. Cbem. Sot., Chem. Commun. 1983,576; J. Chem. Sot.. Perhin Tmns. 1 1985, 1355. Santaniello, E.; Manzocchi, A.; Biondii P. A. J. Chem. Sot., Perhin Tmns. I 1981,307. (b) For the enzymatic preparation of deuteriated alanines, see: Esaki, N.; Sawada, S.; Tanaka, H.; Soda, K. Anal. B&hem. 1982, 119,281. (c) For the photochemicaio-decarboxylation of benzoyl-Asp-OH, see: Nakai, H.; Sato, I.; Mizoguchi, T.; Kanaoka, Y. Synthesis 1982, 141. 17. The preparation ofa-alanine from aspartic acid mimics the action of the enzyme aspartic acid g-decarboxylasc. For a leading reference, see: Chang, C.-C.; Laghai, A.; O’Lcarly, M. H.; Floss, H. G. I: Biol. C’hem. 1982,257,3564. 18. For the synthesis of (S)-Cbz-3-bromoaianine from serine, see: Arnold, L. D.; KaIantar, T. H.; Vederas, J. C. J. Am. Chem. sot. 1985,107,7105.
(Received
in UK 22 June 1990)