Asymmetric Alkylation via Chiral Nucleophilic Catalysis

描述(由申请人提供)： 提出了一种通过手性亲核催化进行硅烯醇醚和硅酮缩醛的催化不对称烷基化反应的策略。预测含有亲核残基的多肽基催化剂既能激活亲硅烷基亲核试剂，又能提供手性环境(通过多肽的二级结构)来诱导烷基化反应中的对映选择性。具体地说，i-丁基组氨酸有望成为一种有效的亲核氨基酸，在此基础上构建这样的多肽催化剂。讨论了在烷基化过程中优化反应活性和选择性的策略，包括催化剂的设计、添加剂的可能益处、反应组分的缓慢添加以及底物的明智选择。建议发展这一方法以包括其他亲核剂的使用，包括取代的烯丙基锡烷和硅烷。此外，还讨论了替代亲电剂的使用，如氧源和卤源。

DESCRIPTION (provided by applicant): A strategy for the catalytic, asymmetric alkylation of silyl enol ethers and silyl ketene acetals via chiral nucleophilic catalysis is presented. Peptide-based catalysts containing a nucleophilic residue are predicted to both activate primary alkyl electrophiles toward attack by the silyl enol nucleophiles and provide a chiral environment (by way of the peptide's secondary structure) to induce enantioselectivity in the alkylation event. Specifically, i-butylhistidine is anticipated to be an effective nucleophilic amino acid upon which to build such peptide catalysts. Strategies for optimizing both reactivity and selectivity in the alkylation process are discussed, including catalyst design, the possible benefit of additives, slow addition of reaction components, and the judicious choice of substrates. Development of this method to encompass the use of other nucleophiles including substituted allylstannanes and silanes is proposed. Additionally, the use of alternative electrophiles such as oxygen and halogen sources is discussed.