Asymmetric Alkylation via Chiral Nucleophilic Catalysis

通过手性亲核催化进行不对称烷基化

• 批准号: 6998078
• 负责人: ELIZABETH A COLBY DAVIE
• 金额: $ 4.21万
• 依托单位: BOSTON COLLEGE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6998078
• 关键词: alkylation; catalyst; chemical addition; chemical substitution; enol; ketene; molecular asymmetry; postdoctoral investigator; stereoisomer

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.

描述（由申请人提供）： 提出了一种手性亲核催化烯醇醚和烯酮缩醛的不对称烷基化反应策略。预测含有亲核残基的肽基催化剂既活化伯烷基亲电试剂朝向甲硅烷基烯醇亲核试剂的攻击，又提供手性环境（通过肽的二级结构）以诱导烷基化事件中的对映选择性。具体地，预期叔丁基组氨酸是构建此类肽催化剂的有效亲核氨基酸。在烷基化过程中的反应性和选择性的优化策略进行了讨论，包括催化剂的设计，添加剂的可能的好处，缓慢添加的反应组分，和明智的选择基板。发展这种方法，包括使用其他亲核试剂，包括取代的烯丙基锡烷和硅烷的建议。此外，使用替代亲电试剂，如氧和卤素源进行了讨论。