Highly enantioselective phase transfer catalyzed alkylation of a 3-oxygenated propionic ester equivalent; applications and mechanism
Highly enantioselective phase transfer catalyzed alkylation of a 3-oxygenated propionic ester equivalent; applications and mechanism
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DOI：
10.1021/ja9835739
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发表时间：
1998-12-16
影响因子：
15
通讯作者：
Busch-Petersen, J
中科院分区：
文献类型：
--
作者：
Corey, EJ;Bo, YX;Busch-Petersen, J
最近详细的分子机制描述了相转移催化的对映选择性烷基化与使用手性季铵盐1a。通过甘氨酸叔丁基-二苯甲酮希夫碱的烷基化反应，制备了一系列(S)- r -氨基酸衍生物（天然的和非天然的），其对映选择性在400:1到60:1之间。在机理模型中，接触离子配对选择性地发生在烯酸酯的阴离子氧和1a的阳离子氮的一个四面体面之间（由于空间原因）。此外，在接触离子对内的烯酸盐和季铵离子上的互补结合位点之间发生了相当大的范德华吸引。静电和范德华结合的结合产生了高度结构化的接触离子对，在这种接触离子对中，亲电的烷基化物质只能接触到烯酸酯亲核R碳的一个面。这一机制图为催化烷基化过程的绝对立体化学过程和观察到的非常高水平的对映选择性提供了逻辑解释。在本文中，我们证明了这种显著的对映选择性烷基化催化剂可以应用于其他烯醇酯，并且对映选择性以可预测的方式随远端取代基对烯醇酯的电子效应而变化。此外，我们提出了烷基化过程的分析，强调了电荷密度和熵在确定对映体选择性水平中的重要性。以4,4′-双-（二甲胺）二苯甲酮（米歇尔酮）为原料，经以下步骤制备γ-不饱和酯2:(1)与γ-锂化丙酸叔丁酯（从丙酸酯上的n-BuLi合成）在THF -15℃中反应20 h (68%)；(2)在23℃条件下，用5%的Pd-BaSO4和1atm的H2催化还原20 min (91%)；(3)用CH3SO2Cl-Et3N-4-N， N-（二甲氨基）-吡啶在CH2Cl2中0℃脱水30 min（86%）。2在含有10mol %手性溴化铵1b的1:1 CH2Cl2-Et2O溶液中与各种溴化烷基或碘化物在固体CsOH， H2O存在下反应顺利，生成R烷基化产物3，收率高，ee高（94-98%），如表1所示。通过与(R)-(+)-2-甲基-3-叔丁基二甲基硅基丙烷- 1,3 -二醇（4，R） CH3), 4 [R] d25 + 13.18 （c 0.19, CHCl3）的化学对比，证实了3，R) CH3的烷基化产物的(R)绝对构型，通过以下顺序：(1)用二异丁基铝氢化物在CH2Cl2 -78°f - 0°c下，在30 min内将CO2t-Bu还原为CH2OH；(2)用叔丁基二甲基硅酰氯(TBSCl)-Et3N-DMF在23℃下进行硅化反应1 h；(3)用催化氧化OsO4和n -甲基啉n -氧化物（NMO）在8:1丙酮- h2o中23℃氧化24 h；(4)在CH2Cl2中与Pb (OAc) 4在0℃下氧化CC裂解1 h；(5)在CH3OH -40℃条件下，用NaBH4将CHO还原为CH2OH。以类似的方法，3，R) C6H5CH2, o-C6H5-C6H4， R) n-C6H13分别以较好的总收率合成了4，R) C6H5CH2, o-C6H5-C6H4， R) n-C6H13。因此，一系列手性2取代单保护丙烷- 1,3 -二醇是对映选择性合成的通用构件，可以通过对映选择性相转移催化2到3的转化来获得。一般的催化对映选择性转化2f3除用于手性化合物的合成外，还具有多种潜在的应用。
A detailed molecular mechanism has recently been described for the phase transfer catalyzed enantioselective alkylation of an enolate with use of the chiral quaternary cinchonidinium salt 1a. 1, 2 This reaction was illustrated by a variety of examples in which a series of (S)-R-amino acid derivatives (both natural and unnatural) was prepared with enantioselectivities in the range 400: 1 to 60: 1 by alkylation of the tert-butyl glycinate-benzophenone Schiff base. 3 In the mechanistic model contact ion pairing takes place selectively between the anionic oxygen of the enolate and just one of the tetrahedral faces of the cationic nitrogen of 1a (for steric reasons). In addition, considerable van der Waals attraction occurs between the enolate and a complementary binding site on the quaternary ammonium cation within the contact ion pair. The combination of electrostatic and van der Waals binding results in a highly structured contact ion pair in which only one face of the nucleophilic R carbon of the enolate is accessible to the electrophilic alkylating species. 1 This mechanistic picture provides a logical explanation for the absolute stereochemical course of the catalytic alkylation process and also the very high levels of enantioselectivity which are observed. In this paper we demonstrate that this remarkably enantioselective alkylation catalyst can be applied to other enolates and that the enantioselectivity varies in a predictable way with the electronic effect of remote substituents on the enolate. In addition, we present an analysis of the alkylation process that underscores the importance of charge density and entropy in determining the level of enantioselectivity. The, γ-unsaturated ester 2 was prepared from 4, 4′-bis-(dimethylamino) benzophenone (Michler’s ketone) by the following sequence:(1) reaction with γ-lithiated tert-butyl propiolate (from n-BuLi on the propiolate ester in THF at-78 C) in THF at-15 C for 20 h (68%);(2) catalytic reduction with 1 atm of H2 over 5% Pd-BaSO4 at 23 C for 20 min (91%); and (3) dehydration with CH3SO2Cl-Et3N-4-N, N-(dimethylamino)-pyridine in CH2Cl2 at 0 C for 30 min (86%). Reaction of 2 in 1: 1 CH2Cl2-Et2O solution containing 10 mol% of chiral ammonium bromide 1b with various alkyl bromides or iodides in the presence of solid CsOH ‚H2O proceeded smoothly to form the R alkylation product 3 in good yield and in high ee (94-98%), as summarized in Table 1. The (R)-absolute configuration for the alkylation products, which was predicted from the mechanistic model, was confirmed for the case of 3, R) CH3, by chemical correlation with (R)-(+)-2-methyl-3-tert-butyldimethylsilylpropane-1, 3-diol (4, R) CH3), 4 [R] D 25+ 13.18 (c 0.19, CHCl3), using the following sequence:(1) reduction of CO2t-Bu to CH2OH with diisobutylaluminum hydride in CH2Cl2 at-78 f 0 C over 30 min;(2) silylation with tert-butyldimethylsilyl chloride (TBSCl)-Et3N-DMF at 23 C for 1 h;(3) oxidation of CdC with catalytic OsO4 and stoichiometric N-methylmorpholine N-oxide (NMO) in 8: 1 acetone-H2O at 23 C for 24 h;(4) oxidative CC cleavage with Pb (OAc) 4 in CH2Cl2 at 0 C for 1 h; and (5) reduction of CHO to CH2OH with NaBH4 in CH3OH at-40 C. In an analogous manner 4, R) C6H5CH2, o-C6H5-C6H4, R) n-C6H13 were synthesized in good overall yield from 3, R) C6H5CH2, o-C6H5C6H4, and n-C6H13, respectively. Thus a range of chiral 2-substituted monoprotected propane-1, 3-diols, versatile building blocks for enantioselective synthesis, can be accessed by enantioselective phase transfer catalyzed conversion of 2 to 3.The general catalytic enantioselective conversion 2 f 3 has a variety of potential applications other than to the synthesis of chiral …