Enantioselective Robinson-Type Annulation Reaction Catalyzed by Chiral Phosphoric Acids
Enantioselective Robinson-Type Annulation Reaction Catalyzed by Chiral Phosphoric Acids
复制标题
DOI：
10.1002/anie.200901127
复制
发表时间：
2009-01-01
影响因子：
16.6
通讯作者：
Mori, Keiji
中科院分区：
文献类型：
--
作者：
Akiyama, Takahiko;Katoh, Takuya;Mori, Keiji
罗宾逊环合反应是构建环己烯酮结构的重要方法之一，广泛应用于复杂天然产物的合成。[1]它由三个连续的过程组成：1）羰基化合物与α，β不饱和酮的Michael加成，2）分子内Aldol反应，3）脱水。在罗宾逊成环反应中，酸催化剂和碱催化剂都得到了广泛的应用。为了用罗宾逊成环反应合成光学纯形式的环己烯酮亚结构，使用手性酮作为起始原料，并通过非对映选择性迈克尔加成反应提供对映体富集的罗宾逊成环产物。[2]另外，对映选择性Michael加成反应是对映选择性罗宾逊成环反应的关键反应。[3]在20世纪70年代，赫尔曼和温伯格进行了开创性的工作，在金鸡纳生物碱作为催化剂的存在下，β-酮酯与甲基乙烯基酮的对映选择性共轭加成。[4，5] Sasai和Shibasaki公开了β-酮酯与甲基乙烯基酮的高度对映选择性共轭加成反应。[6]手性钪（III）催化剂，[7]钯催化剂，[8]和钌催化剂[9]也已被采用。Maruoka和同事报道了相转移催化。[10]最近，邓和同事开发了一种有效的金鸡纳生物碱催化剂。[11]在我们正在进行的磷酸催化合成方法的研究中，[12-14]我们发现了一种用于对映选择性Robinson型成环反应的新策略，包括：1）手性Brønsted酸催化α-烷基-β-酮酯与甲基乙烯基酮的不对称Michael加成反应，和2）在分子内羟醛缩合反应中的手性布朗斯台德酸催化动力学拆分，随后脱水。通过Michael加成反应选择性地获得的对映体优先反应，得到具有优异的对映选择性的相应Robinson型成环产物（方案1）。首先，我们考察了β-酮酸酯3a（X= Y= H，Z= CH_2）与甲基乙烯基酮在手性磷酸存在下的Michael加成反应。磷酸的筛选揭示磷酸1作为迈克尔加成反应的催化剂是最有效的。
The Robinson annulation reaction is one of the most useful methods for the construction of the cyclohexenone structure and is widely employed in the synthesis of complex natural products.[1] It consists of three consecutive processes: 1) Michael addition of a carbonyl compound to an α, βunsaturated ketone, 2) an intramolecular aldol reaction, and 3) dehydration. Both acid and base catalysts have been extensively utilized in the Robinson annulation reaction. To synthesize the cyclohexenone substructures in an optically pure form with the Robinson annulation reaction, a chiral ketone is used as the starting material and an enantioenriched Robinson annulation product is furnished by the diastereoselective Michael addition reaction.[2] Alternatively, the enantioselective Michael addition reaction is a key reaction for the enantioselective Robinson annulation reaction.[3] In the 1970s Hermann and Wynberg conducted seminal work on the enantioselective conjugate addition of β-keto esters to methyl vinyl ketone in the presence of cinchona alkaloid as catalyst.[4, 5] Sasai and Shibasaki disclosed the highly enantioselective conjugate addition reaction of β-keto esters with methyl vinyl ketone.[6] Chiral scandium (III) catalysts,[7] palladium catalysts,[8] and ruthenium catalysts [9] have been also employed. Maruoka and co-workers have reported phasetransfer catalysis.[10] Recently, Deng and co-workers have developed an efficient cinchona alkaloid catalyst.[11] In our ongoing studies of synthetic methods which are catalyzed by phosphoric acid,[12–14] we found a novel strategy for the enantioselective Robinson-type annulation reaction which includes: 1) a chiral Brønsted acid catalyzed enantioselective Michael addition reaction of α-alkyl-β-keto esters with methyl vinyl ketone, and 2) a chiral Brønsted acid catalyzed kinetic resolution in the intramolecular aldol reaction followed by dehydration. The enantiomer that was obtained selectively by the Michael addition reaction reacted preferentially to give the corresponding Robinson-type annulation product with excellent enantioselectivities (Scheme 1). Herein, we wish to describe the details of our strategy.At the outset, the Michael addition reaction of β-keto ester 3a (X= Y= H, Z= CH2) with methyl vinyl ketone in the presence of a chiral phosphoric acid was examined. Screening for the phosphoric acid revealed that phosphoric acid 1 was the most effective as a catalyst for the Michael