γ—手性—α,β—不饱和醛与二烷基铜锂的立体选择性反应

Stereoselective Reactions of Chiral y-Amino Enals with Cuprates

本文研究了在γ-手性-α,β-不饱和醛④的一些亲核加成反应中的1,4-不对称诱导效应。研究结果表明:共轭烯醛④与格氏类试剂(RM)的1,2-亲核加成反应,未表现出有意义的非对映立体选择性,这意味着在这类反应中可能存在的电子和立体效应无法通过传递双键系统传递;而在助剂(氯化三甲基硅烷、六甲基磷酸三酰胺和三乙胺)存在下,化合物④和二烷基铜锂的反应,导致了大于98％的1,2-加成选择性和优良的非对映立体选择性(82～95％)。这说明在后者反应中,γ-位的不对称信息已成功地通过π-电子系统进行了传递,从而产生了一个远距离的1,4-不对称诱导效应。通过对反应中立体因素的考察,证实共轭烯醛④中β-位立体阻碍是产生高度的1,2-加成选择性的原因;而饱和醛和共轭烯醛竞争反应的实验结果显示:在与二烷基铜锂的加成反应中,共轭烯醛具有较高的反应活性。因而,作者提议反应的第一步是选择性形成d,π-化合物,然后发生立体选择性的1,2-加成反应。

In this paper, the possibility of 1, 4-asymmetric induction in some nucleophilic reactions of the chiral enals (4) was investigated. Upon reaction of the enals (4) with various Grignard-type reagents, essentially stereorandom behaviour was observed. This indicates that possible electronic and steric effects are not transmitted through or across the alkene n-system in these reactions. In striking contrast, the reactions of cuprates R2CuLi in the presence of the Me3SiCl, hexamethylphosphoric triamide (HMPA) and triethylamine led to high levels of 1, 2-regioselectivity (>98%) and diastereoselectivity (ds: 82-95%). Both regioselectivity and 1, 4-asymmetric induction are novel. This means that chiral information is transferred successfully through the double bond so that a remote 1, 4-asymmetric induction results. The control experiments show that the stenc factor is very important in this transformation. If B-position of the enal bears a large proup, the reaction proceeds preferentially along the 1, 2-path. The competition reactions between saturated aldehydes and the enals show that the enals have a higher reactivity in cuprate addition reactions. Thus, the above mentioned reaction mechanism is proposed, in which the initial step is n-facially selectived, n-complexation, followed by stereoselective 1, 2-addition at the terminus of the it-system in the s-trans conformation to provide the main diastereoisomer.