甘氨酸衍生的二苯甲酮席夫堿在奎寧類手性相轉移催化劑催化下與鹵代物進行烷基化不對稱合成手性α-氨基酸的反應。底物1（甘氨酸陰離子等價物）可以和鹵代烴進行反應。底物5（甘氨酸陽離子等價物）可以和烷基硼烷反應得到氨基酸。
反應機理
反應實例
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】
相關文獻
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
編譯自
一、Organic Syntheses Based On Name Reactions, 3RdEd, A. Hassner, 207-208
二、APP: ReactionFlash
