Asymmetric synthesis by alkylation of alpha, beta-unsaturated aldehyde hydrazones

α,β-不饱和醛腙的烷基化不对称合成

• 批准号: 05650887
• 负责人: YAMASHITA Masakazu
• 金额: $ 1.22万
• 依托单位: Doshisha University, Faculty of Engineering
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1993
• 资助国家: 日本
• 起止时间: 1993 至 1994
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-05650887/
• 关键词: Asymmetric carbon; Hydrazones; Asymmetric synthesis; Alkylation; Aldehydes; Nitriles; 不斉アルキル化反応; alpha-ビニルアルデヒド; 転位反応; alpha,beta-不飽和アルデヒドヒドラゾン; 不斉第4級炭素原子

Enantio-and regioselective alkylation of alpha, beta-unsaturated aldehyed hydrazones or imines to alpha-alkyl-beta, gamma-unsaturated carbonyl compounds are described.2-Alkyl-2-methyl-3-butenal which has quaternary carbon atom at alpha-position was synthesized from 2-methyl-2-butenal cyclohexylimine by successive deprotonation by base, alkylation, and the following hydrolysis. This shows that alkylation occurred at alpha-position selectively and the alpha, beta-unsaturated double bond migrated to beta, gamma.Similar results were obtained using hydrazone derivatives such as dimethylhydrazones instead of cyclohexylimines. 2-Alkyl-2-methyl-3-butenal was obtained from these dimethylhydrazones by hydrolysis with copper (II) choride. When magnesium mono-peroxyphthalate was used, 2-methyl-2-butenonitrile which has quaternary carbon atom at alpha-position were produced from these dimethylhydrazones in good yields.When chiral hydrazones such as 2-methyl-2-butenal SAMP ( (S) -1-amino-2- (methoxymethyl) pyrrolidine) hydrazone were used, chiral nitriles were produced in good enantioselectivity. The absolute configuration of (-) -2-benzyl-2-methyl-3-butenonitrile was elucidated as (R) -series by chemical correlation with (S) - (+) -methyl 2-cyano-2-methyl-3-phenylpropionate, whose absolute configuration is already established.Moreover, chiral aldehydes which have asymmetric quaternary carbon atom at alpha-position were produced in moderate enantioselectivity when chiral imines such as 2-methly-2-butenal (S,S) -ADPD ( (4S,5S) - (+) -5-amino-2,2-dimethyl-4-phenyl-1,3-dioxane) imine were used.

本发明描述了α，β-不饱和取代腙或亚胺的对映和区域选择性烷基化反应，合成了α-烷基-β，γ-不饱和羰基化合物。以2-甲基-2-丁烯醛环己亚胺为原料，经碱脱质子、烷基化、水解等步骤，合成了α-位含季碳原子的2-烷基-2-甲基-3-丁烯醛。这表明，烷基化发生在α-位置选择性和α，β-不饱和双键迁移到β，γ。使用腙衍生物，如二甲基腙，而不是环己基亚胺得到类似的结果。用氯化铜水解这些二甲基腙得到2-烷基-2-甲基-3-丁烯醛。当使用单过氧邻苯二甲酸镁时，这些二甲基腙以较好的产率生成α位上含季碳原子的2-甲基-2-丁烯腈，当使用手性腙如2-甲基-2-丁烯醛SAMP（（S）-1-氨基-2-（甲氧基甲基）吡咯烷）腙时，以较好的对映选择性生成手性腈。（-）-2-苄基-2-甲基-3-丁烯腈的绝对构型通过与（S）-（+）-甲基2-氰基-2-甲基-3-苯基丙酸酯的化学关联确定为（R）系列，在α-位上具有不对称季碳原子的手性醛以中等的对映选择性由手性亚胺如2-甲基-2-使用丁烯醛（S，S）-ADPD（（4S，5S）-（+）-5-氨基-2，2-二甲基-4-苯基-1，3-二氧六环）亚胺。