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

以2-甲基-2-丁烯基环己亚胺为原料，经碱去质子化、烷基化、水解制得2-烷基-2-甲基-3-丁烯醛，α位含四碳原子。这表明烷基化反应选择性地发生在α-位，α，β-不饱和双键转移到了β，伽马。类似的结果也是用肼类化合物如二甲肼取代环己亚胺得到的。2-烷基-2-甲基-3-丁烯醛通过氯化铜(II)的水解制得。以过氧邻苯二甲酸镁为原料，高产率地合成了α-位含季碳原子的2-甲基-2-丁烯腈；使用2-甲基-2-丁烯醛((S)-1-氨基-2-(甲氧基甲基)吡咯烷)肼等手性肼类化合物，手性腈的对映选择性较好。通过与已确定绝对构型的(S)-(+)-2-氰基-2-甲基-3-苯基丙酸甲酯的化学关联，确定了(-)-2-苄基-2-甲基-3-丁烯腈的绝对构型为(R)-系列。此外，当2-甲基-2-丁烯醛(S，S)-ADPD((4S，5S)-(+)-5-氨基-2，2-二甲基-4-苯基-1，3-二恶烷)亚胺。

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.