LETTER
Stereoselective -Alkylations, 1,4-Additions, and One-pot 1,4-Addition/ -Methylations
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mixture of 4S/R as a colorless oil (e.r. of the corresponding
2-methyl-3-phenylpropanol = 95:5, chiral HPLC analysis).
(12) The configuration of the newly introduced stereogenic
carbon in 4S was determined to be S by comparing the [ ]D
sign of 2-methyl-3-phenylpropanol {[ ]19D –10.7 (c 0.64,
benzene)}, obtained by the reductive removal (DIBAL-H,
CH2Cl2, –78 °C to –18 °C) of the carbohydrate template 1
from 4S, to the reported sign for (R)-2-methyl-3-phenyl-
propanol {[ ]D+11.0 (c 1.15, benzene)}, see: Ref. 2a.
(13) We tried to trap the enolate formed from 2 (NaHMDS, THF,
–78 °C to –18 °C) with TBSCl or TMSCl to verify the
geometry of the enolate. In both cases, unfortunately, we
could not obtain the silylated enolate. The substrate 2 was
recovered quantitatively after quenching with water.
(14) For a typical procedure for the 1,4-addition of an
organocopper reagent to structurally resembling
References
(1) For reviews on asymmetric synthesis using natural products-
induced asymmetric environments, see: (a) Evans, D. A.;
Takacs, J. M.; McGee, L. R.; Ennis, M. D.; Mathre, D. J.;
Bartroli, J. Pure Appl. Chem. 1981, 53, 1109.
(b) Asymmetric Synthesis, Vol. 2; Morrison, J. D., Ed.;
Academic Press: New York, 1983. (c) Asymmetric
Synthesis, Vol. 3; Morrison, J. D., Ed.; Academic Press:
New York, 1984. (d) Oppolzer, W. Tetrahedron 1987, 43,
1969. (e) Seden-Penne, J. Chiral Auxiliaries and Ligands in
Asymmetric Synthesis; Wiley: New York, 1995. (f) Rück,
K.; Kunz, H. Chiral Auxiliaries in Cycloadditions; Wiley:
New York, 1995. (g) Enders, D.; Klatt, M. Synthesis 1996,
1403. (h) Groaning, M. D.; Meyers, A. I. Tetrahedron 2000,
56, 9843.
(2) For representative asymmetric -alkylations of esters using
chiral auxiliaries, see: (a) Evans, D. A.; Ennis, M. D.;
Mathre, D. J. J. Am. Chem. Soc. 1982, 104, 1737.
(b) Lutomski, K. A.; Meyers, A. I. Asymmetric Synthesis,
Vol. 3; Morrison, J. D., Ed.; Academic Press: New York,
1983, 213. (c) Enders, D. Asymmetric Synthesis, Vol. 3;
Morrison, J. D., Ed.; Academic Press: New York, 1983,
275. (d) Oppolzer, W.; Dudfield, P.; Stevenson, T.; Godel,
T. Helv. Chim. Acta 1985, 68, 212. (e) Oppolzer, W.;
Rodriguez, I.; Starkemann, C.; Walther, E. Tetrahedron Lett.
1990, 31, 5019. (f) Sarakinos, G.; Corey, E. J. Org. Lett.
1999, 1, 1741.
(3) For representative examples of the 1,4-additions to
unsaturated carbonyl compounds incorporated into chiral
auxiliaries, see: (a) Tomioka, K.; Suenaga, T.; Koga, K.
Tetrahedron Lett. 1986, 27, 369. (b)Oppolzer, W.;Kingma,
A. J.; Poli, G. Tetrahedron 1989, 45, 479. (c) Amberg, W.;
Seebach, D. Chem. Ber. 1990, 123, 2413. (d) Enders, D.;
Vazquez, J. Synlett 1999, 629.
(4) Totani, K.; Nagatsuka, T.; Takao, K.; Ohba, S.; Tadano, K.
Org. Lett. 1999, 1, 1447.
(5) Totani, K.; Nagatsuka, T.; Yamaguchi, S.; Takao, K.; Ohba,
S.; Tadano, K. J. Org. Chem. 2001, 66, 5965.
(6) Munakata, R.; Totani, K.; Takao, K.; Tadano, K. Synlett
2000, 979.
(7) Nagatsuka, T.; Yamaguchi, S.; Totani, K.; Takao, K.;
Tadano, K. Synlett 2001, 481.
glucopyranosidic templates, see Refs 4 and 5.
(15) The 1,4-addition to 5 of the phenyl Grignard reagent in the
absence of CuBr Me2S provided the corresponding 1,2-
addition product in a reduced yield.
(16) The absolute configurations of the newly introduced
stereogenic carbon ( -carbon) in the major adducts 6Re and
7Re were determined by comparing the sign of 3-methyl-
pentanoic acid (from 6Re)or 3,4,4-trimethylpentanoic acid
(from 7Re), obtained by the hydrolytic removal of the
carbohydrate template, with the reported [ ]D data.6 The
absolute configuration of the -carbon in 8Re was
determined to be R by comparing the [ ]D sign of
enantioenriched 3-phenylbutanoic acid {[ ]23D –44.4
(c 1.4, benzene)}, prepared from 8Re by the hydrolytic
removal of 1, to that for the known (R)-enantiomer {[ ]20
D
–51 (c 1, benzene)}, see: Grimshaw, J.; Millar, P. G. J.
Chem. Soc. (C) 1970, 2324.
(17) For some publications on the 1,4-additions of organolithium,
see: (a) Seebach, D.; Ertas, R.; Locher, R.; Schweizer, W. B.
Helv. Chim. Acta 1985, 68, 264. (b) Cohen, T.; Yu, L. C. J.
Org. Chem. 1985, 50, 3266. (c) Cooke, M. P. Jr. J. Org.
Chem. 1986, 51, 1637. (d) Plunian, B.; Mortier, J.; Vaultier,
M. J. Org. Chem. 1996, 61, 5206. (e) Shindo, M.; Koga, K.;
Asano, Y.; Tomioka, K. Tetrahedron 1999, 55, 4955.
(18) The 1,4-addition of phenyllithium to 5 (entry 6): To a cooled
(–78 °C) solution of 5 (156 mg, 0.329 mmol) in THF (3 mL)
was added PhLi (1.04 M solution in cyclohexane–ether, 0.48
mL, 0.499 mmol). After being stirred at -78 °C for 15 min,
the solution was quenched with sat. aq. NH4Cl. The mixture
was diluted with EtOAc (10 mL) and washed with sat. aq.
NH4Cl (5 mL 3). The organic layer was dried (Na2SO4)
and concentrated in vacuo. The residue was purified by
column chromatography on silica gel (EtOAc/hexane, 1:70)
to give 167 mg (92%) of an inseparable mixture of 8Si/Re as
a colorless oil (e.r. of 3-phenylbutanol = 97:3, chiral HPLC
analysis).
(19) For the notation of s-trans, syn- or s-cis, syn-conformations,
see: Eliel, E. L.; Wilen, S. H.; Mander, L. N. Stereochemisty
of Organic Compounds; John Wiley & Sons, Inc.: New
York, 1994, 889; see also, ref. 20d..
(20) (a) Oppolzer, W.; Löher, H. Helv. Chim. Acta 1981, 64,
2808. (b) Oppolzer, W. Angew. Chem., Int. Ed. Engl. 1984,
23, 876. (c) Loncharich, R. J.; Schwartz, T. R.; Houk, K. N.
J. Am. Chem. Soc. 1987, 109, 14. (d) Mezrhab, B.; Dumas,
F.; d' Angelo, J.; Riche, C. J. Org. Chem. 1994, 59, 500.
(21) We also examined to trap of the intermediary enolate formed
after the 1,4-addition of a phenyl nucleophile to 5 (PhLi, –78
°C) with TMSCl. The 1,4-adduct 8Si was isolated solely and
the expected silylated enolate could not be obtained.
(8) For recent reviews on the asymmetric synthesis achieved on
carbohydrate templates, see: (a) Cintas, P. Tetrahedron
1991, 47, 6079. (b) Kunz, H.; Rück, K. Angew. Chem., Int.
Ed. Engl. 1993, 32, 336. (c) Hultin, P. G.; Earle, M. A.;
Sudharshan, M. Tetrahedron 1997, 53, 14823.
(9) All new compounds were fully characterized by 1H and 13
C
NMR, IR and HRMS after chromatographic purification on
silica gel.
(10) The 4-O-acyl derivatives 2 and 3 were prepared from 1. For
2: (CH3CH2CO)2O, DMAP, pyr., 80 °C (98%). For 3:
LiHMDS, PhCH2CH2C(O)Cl, Et2O, –78 °C (83%, 15%
recovery of 1).
(11) A typical procedure for the -benzylation of 4-O-propionyl
ester 2: To a cooled (–78 °C) solution of 2 (47.5 mg, 0.103
mmol)in THF (1 mL) was added NaHMDS (1.0 M solution
in THF, 0.11 mL, 0.11 mmol). The solution was stirred at -
78 °C for 15 min, then BnBr (18.5 L, 0.156 mmol) was
added. After being stirred at -78 °C for 15min, then at –18
°C for 15 min, the reaction mixture was quenched with sat.
aq. NH4Cl. The mixture was diluted with EtOAc (10 mL)
and washed with sat. aq. NH4Cl (5 mL 3). The organic
layer was dried (Na2SO4) and concentrated in vacuo. The
residue was purified by column chromatography on silica
gel (toluene) to give 55.1 mg (97%) of an inseparable
Synlett 2001, No. 11, 1772–1776 ISSN 0936-5214 © Thieme Stuttgart · New York