O’Donnell氨基酸合成反应

甘氨酸衍生的二苯甲酮席夫碱在奎宁类手性相转移催化剂催化下与卤代物进行烷基化不对称合成手性α-氨基酸的反应。底物1（甘氨酸阴离子等价物）可以和卤代烃进行反应。底物5（甘氨酸阳离子等价物）可以和烷基硼烷反应得到氨基酸。

反应机理

反应实例

tert-Butyl N-(diphenylmethylene)-4-fluoro-b-(4-fluorophenyl)-L-phenylalaninate (2). Schiff base 1(1.8 kg, 6.1 mol, prepared from benzophenone imine and t-butyl glycinate hydrochloride2) was added to 4,40-diflurorbenzhydryl bromide (1.2 equiv) in 1.8 L DCM followed by the cinchonidine-derived catalyst 4 (5 mol %) and the mixture was cooled to 0 ℃. Aq KOH (45% solution, 10 equiv) was added over 15–30 min at 0–5 ℃ and the two-phase mixture was stirred for 5 h. Workup of crude product (80:20 er) followed by recrystallization from EA:heptane afforded 1.72 kg of 3 (56%, >99% ee), mp 168–171 ℃.

【Org Process Res Dev., 2007, 11, 624】

tert-Butyl N-(diphenylmethylene)-2-acetoxyglycinate (5). Schiff base 1 (14.7 g, 0.05 mol) and lead tetraacetate (24.4 g, 0.055 mol) in DCM (150 mL) were stirred at r.t. for 5 h. Workup of the crude product followed by recrystallization from hexane afforded 16.2 g of 5 (92%), mp 105–106 ℃.

【J Am Chem Soc.， 1996， 118， 6070】

【Organic Letters, 2005, 7, 1129-1131】

【Tetrahedron Asymmetry, 2009, 20, 2600-2608】

相关文献

1 O’Donnell MJ Tet Lett 1978 2641, 4625

2 O’Donnell MJ J Org Chem 1982 47 2663

3 O’Donnell MJ Tet Lett 1985 26 695, 699

4 O’Donnell MJ J Am Chem Soc 1989 111 2353

5 de Meijere A Synlett 1995 226

6 O’Donnell MJ Tet Asymm 1996 7 621

7 O’Donnell MJ J Am Chem Soc 1996 118 6070

8 Lygo B Tet Lett 1997 38 8595

9 Corey EJ J Am Chem Soc 1997 119 12414

10 O’Donnell MJ Tet Lett 1998 39 8775

11 O’Donnell MJ Tetrahedron 1999 55 6347

12R O’Donnell MJ Aldrichim Acta 2001 34 3

13 O’Donnell MJ J Am Chem Soc 2002 124 9348

14 O’Donnell MJ Acc Chem Res 2004 37 506

15 Maruoka K Chem Rev 2007 107 5656

16 Patterson DE Org Process Res Dev 2007 11 624

17 Scott WL J Am Chem Soc 2007 129 7077

18 Scott WL Org Lett 2009 11 3558

编译自

一、Organic Syntheses Based On Name Reactions, 3RdEd, A. Hassner, 207-208

二、APP: ReactionFlash