Germanium(II)-Mediated Reductive Cross-Aldol Reaction of Bromoaldehydes with Aldehydes: NMR Studies and ab Initio Calculations

A highly practical reductive cross-aldol reaction of α-bromoaldehydes with various aldehydes has been developed using Ge(II)Cl2 to produce aldehyde germanium(IV) aldolates, which were directly transformed to various multifunctionalized compounds. A remarkable change in stereoselectivity depended on the α-bromoaldehydes employed; secondary α-bromoaldehydes gave syn selectivities, while tertiary α-bromoaldehydes accomplished the synthesis of anti-selective aldol products with a quaternary carbon center. NMR studies and X-ray analysis strongly suggested the formation of germanium enolate in the reaction of α-bromoaldehyde 2h with GeCl2−dioxane. Detailed mechanistic studies, including NMR analysis and ab initio calculations, revealed the generation of stable germanium aldolates, which was due to the remarkably low Lewis acidity of the germanium(IV).

本研究开发了一种实用性极强的α-溴代醛（α-bromoaldehydes）与多种醛之间的还原交叉羟醛缩合反应，以二氯化锗(II)（Ge(II)Cl2）为试剂，生成醛基锗(IV)羟醛加合物（aldehyde germanium(IV) aldolates），该中间体可直接转化为多种多官能团化化合物。反应的立体选择性会因所使用的α-溴代醛不同而发生显著变化：二级α-溴代醛可得到顺式选择性产物，而三级α-溴代醛则可合成带有季碳中心的反式选择性羟醛缩合产物。通过核磁共振波谱（NMR）研究与X射线衍射分析，我们有力证实，在α-溴代醛2h与二氧六环合二氯化锗(II)（GeCl2−dioxane）的反应中生成了锗烯醇盐（germanium enolate）。包括核磁共振波谱分析与从头算量子化学计算（ab initio calculations）在内的详细机理研究表明，稳定的锗(IV)羟醛加合物之所以能够生成，是因为锗(IV)具有极低的路易斯酸性（Lewis acidity）。