A chiral nonracemic enolate with dynamic axial chirality: Direct asymmetric α-methylation of α-amino acid derivatives

Angewandte Chemie - International Edition

Volumn 39, Issue 12, 2000, Pages 2155-2157

  Kawabata, Takeo ^a   Suzuki, Hideo ^a   Nagae, Yosikazu ^a   Fuji, Kaoru ^a  

^a KYOTO UNIVERSITY   (Japan)

Author keywords

Alkylations; Amino acids; Asymmetric synthesis; Chirality; Enolates

Indexed keywords

AMINO ACID DERIVATIVE;

ARTICLE; CHEMICAL BOND; CHEMICAL STRUCTURE; CHIRALITY; ENANTIOMER; METHYLATION; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0034674351     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/1521-3773(20000616)39:12<2155::AID-ANIE2155>3.0.CO;2-N     Document Type: Article

References (26)

1. T. Kawabata, K. Yahiro, K. Fuji. J. Am. Chem. Soc. 1991, 113, 9694-9697.
2. T. Kawabata, T. Wirth, K. Yahiro, H. Suzuki, K. Fuji, J. Am. Chem. Soc. 1994, 116, 10809-10810.
3. K. Fuji, T. Kawabata, Chem. Eur. J. 1998, 4, 373-397.
4. Formation of a stereogenic nitrogen atom by coordination with a metal cation has been claimed: D. Sato, H. Kawasaki, I. Shimada, Y. Arata, K. Okamura, T. Date, K. Koga, J. Am. Chem. Soc. 1992, 114, 761-763.
5. Asymmetric reactions through chiral enolate intermediates are described in the reviews: a) D. Seebach, A. R. Sting, M. Hoffmann, Angew. Chem. 1996, 108, 2880-2921; Angew. Chem. Int. Ed. Engl. 1996, 35, 2708-2748;
6. Asymmetric reactions through chiral enolate intermediates are described in the reviews: a) D. Seebach, A. R. Sting, M. Hoffmann, Angew. Chem. 1996, 108, 2880-2921; Angew. Chem. Int. Ed. Engl. 1996, 35, 2708-2748;
7. b) J. Clayden, Angew. Chem. 1997, 109, 986-988; Angew. Chem. Int. Ed. Engl. 1997, 36, 949-951;
8. b) J. Clayden, Angew. Chem. 1997, 109, 986-988; Angew. Chem. Int. Ed. Engl. 1997, 36, 949-951;
9. c) T. Wirth, Angew. Chem. 1997, 109, 235-237; Angew. Chem. Int. Ed. Engl. 1997, 37, 225-227.
10. c) T. Wirth, Angew. Chem. 1997, 109, 235-237; Angew. Chem. Int. Ed. Engl. 1997, 37, 225-227.
11. For examples of asymmetric α-substitution of α-amino acid derivatives without employing external chiral sources, see a) D. Seebach, D. Wasmuth, Angew. Chem. 1981, 93, 1007; Angew. Chem. Int. Ed. Engl. 1981, 20, 971;
12. For examples of asymmetric α-substitution of α-amino acid derivatives without employing external chiral sources, see a) D. Seebach, D. Wasmuth, Angew. Chem. 1981, 93, 1007; Angew. Chem. Int. Ed. Engl. 1981, 20, 971;
13. b) B. Beagley, M. J. Betts, R. G. Pritchard, A. Schofield, R. J. Stoodley, S. Vohra, J. Chem. Soc. Chem. Comm. 1991, 924-925;
14. c) M. J. Betts, R. G. Pritchard, A. Schofield, R. J. Stoodley, S. Vohra, J. Chem. Soc. Perkin 1 1999, 1067-1072.
15. A chiral nonracemic enolate has been claimed as a possible intermediate of an asymmetric rearrangement: T. Gees, W. B. Schweizer, D. Seebach, Helv. Chim. Acta. 1993, 76, 2640-2653.
16. A reaction of 3 is briefly described in reference [3].
17. 2S, 2) 1M NaOH, 3) 47% aq HBr.
18. 17 and 18 were separately isolated in 56% and 27% yield, respectively. Each of them exists as a mixture of N-Boc E/Z isomers (4:1 for 17 and 5:1 for 18).
19. The absolute configuration of D and E is shown provisionally.
20. The half-life at -78°C was roughly estimated on the assumption that ΔS‡ of the restricted bond rotation is nearly zero.
21. The Z and E enolate intermediates should afford α-methylated products of the same absolute configuration, since the 2:1 geometric mixture of enolates gave the product of 81% ee in 96% yield (Table 1, entry 1).
22. The most stable conformation F of 3 was generated by molecular modeling search with the MM3* force field using MacroModel V6.0: a) G. Chang, W. C. Guida, W. C. Still, J. Am Chem. Soc. 1989, 111, 4379-4386;
23. b) I. Kolossváry, W. C. Guida, J. Am. Chem. Soc. 1996, 118, 5011-5019.
24. 1. The difference may increase at the transition state for deprotonation as a result of the enhanced steric interactions in the presence of a base.
25. The 2,3-dihydroxazole ring in the potassium enolate generated from 21 and KHMDS is supposed to be nearly planar.
26. A mixed aggregate of an achiral enolate with an undeprotonated starting material was considered as another possible intermediate for asymmetric induction. This was eliminated by a crossover experiment between 3 and 7: A 1:1 mixture of racemic 3 and (S)-7 (> 99% ee) was α-methylated according to the procedure in Table 1 and afforded racemic 4 (79% yield) and (S)-8 (74% ee, 79% yield), respectively.