Abbasov Mikail E, Hudson Brandi M, Tantillo Dean J, Romo Daniel
Department of Chemistry and Biochemistry , Baylor University , One Bear Place 97348 , Waco , Texas 76798 , USA.
Department of Chemistry , University of California-Davis , One Shields Avenue , Davis , California 95616 , USA . Email:
Chem Sci. 2017 Feb 1;8(2):1511-1524. doi: 10.1039/c6sc04273b. Epub 2016 Oct 21.
Chiral α,β-unsaturated acylammonium salts are novel dienophiles enabling enantioselective Diels-Alder-lactonization (DAL) organocascades leading to - and -fused, bicyclic γ- and δ-lactones from readily prepared dienes, commodity acid chlorides, and a chiral isothiourea organocatalyst under mild conditions. We describe extensions of stereodivergent DAL organocascades to other racemic dienes bearing pendant secondary and tertiary alcohols, and application to a formal synthesis of (+)-dihydrocompactin is described. A combined experimental and computational investigation of unsaturated acylammonium salt formation and the entire DAL organocascade pathway provide a rationalization of the effect of Brønsted base additives and enabled a controllable, diastereodivergent DAL process leading to a full complement of possible stereoisomeric products. Evaluation of free energy and enthalpy barriers in conjunction with experimentally observed temperature effects revealed that the DAL is a rare case of an entropy-controlled diastereoselective process. NMR analysis of diene alcohol-Brønsted base interactions and computational studies provide a plausible explanation of observed stabilization of transition-state structures through hydrogen-bonding effects.
手性α,β-不饱和酰铵盐是新型亲双烯体，可实现对映选择性狄尔斯-阿尔德-内酯化（DAL）有机串联反应，在温和条件下，以易于制备的二烯、市售酰氯和手性异硫脲有机催化剂为原料，生成并稠合的双环γ-和δ-内酯。我们描述了立体发散性DAL有机串联反应扩展到其他带有仲醇和叔醇侧基的外消旋二烯，并描述了其在（+）-二氢康百丁的形式合成中的应用。对不饱和酰铵盐形成和整个DAL有机串联反应途径进行的实验和计算相结合的研究，为布朗斯特碱添加剂的作用提供了合理化解释，并实现了可控的、非对映发散性DAL过程，从而得到所有可能的立体异构产物。结合实验观察到的温度效应评估自由能和焓垒，结果表明DAL是熵控制的非对映选择性过程的罕见实例。对二烯醇-布朗斯特碱相互作用的NMR分析和计算研究，为通过氢键效应观察到的过渡态结构稳定性提供了合理的解释。
