New Methods for Stereoselective Addictions to Carbonyls

描述(由申请人提供)：本建议的目的是在天然产物的全合成的背景下，有时在与羰基化合物的反应之外发现新的反应性。具体目标包括完成氧代多烯大环内酯类抗生素RK-397的合成。我们已经准备了一个后期中间体，在下一个资金阶段，我们将完成这一合成。我们还将研究类似于山本分子间乙烯基羟醛的分子内醇醛反应，并将该方法应用于细胞毒性大环内酯芳烯内酯的合成。我们还将研究一种基于C-硅烷化酯作为亲核成分进行分子内Aldol反应的新策略。这些化合物与醛是相容的，只有在活化时才能反应。在过去的资助期间，我们还开发了一种有趣的不对称O-亲核催化剂，用于对映体选择性酰基转移。该催化剂目前对α-乙酰氧基-N-酰基噻唑硫酮的甲醇分解反应的S值达31。我们将在即将到来的资助期探索这一催化剂系统，并说明其范围和局限性。

DESCRIPTION (provided by applicant): The aims of this proposal are to discover new reactivity in addition reactions to carbonyl compounds, at times in the context of the total synthesis of natural products. Specific aims include completion of the synthesis of the oxo-polyene macrolide antibiotic RK-397. We have prepared a late stage intermediate and in the next funding period, we will complete this synthesis. We will also study an intramolecular vinylogous aldol reaction similar to the Yamamoto intermolecular vinylogous aldol and we will apply this method to the synthesis of the cytotoxic macrolide, arenolide. We will also study a new strategy for conducting intramolecular aldol reactions based on using C-silylated esters as the nucleophilic component. These compounds are compatible with aldehydes and should react only upon activation. We have also developed an interesting asymmetric O-nucleophilic catalyst for enantioselective acyl transfer in the past funding period. This catalyst currently displays s-values of up to 31 for the methanolysis of alpha-acetoxy N- acylthiazolidinethiones. We will explore this catalyst system in the upcoming funding period and delineate its scope and limitations.