Studies on the construction of multi-contiguous asymmetric synthesis using mercapto alcohol as a chiral template

以巯基醇为手性模板的多重连续不对称合成的构建研究

• 批准号: 13470474
• 负责人: NODE Manabu
• 金额: $ 5.7万
• 依托单位: Kyoto Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-13470474/
• 关键词: mercapto alcohol; Michael addition; MPV reduction; dimethylchloroaluminum; three contiguous chiral centers; pentafluorobenzoic acid; odorless thiol; odorless sulfide; メルカプト基; キラルアルコール; Michael付加; γ-ブチロラクトン; 光学活性メルカプトアルコール; 1,3-オキサチアン; [4+2]c

We report herein the highly stereoselective construction of three contiguous stereogenic centers in tandem Michael addition and Meerwein-Ponndorff-Verley (MPV) reduction of the α,β-unsaturated ketones with chiral mercapto alcohol. The reaction of α,β-unsaturated ketones with (-)-10-mercaptoisobornenol in the presence of Me_2AlCl involved asymmetric protonation at ctposition in the Michael addition step and 1,i-hydride shift to reduce carbonyl group. Since the mercapto alcohol behaves as a chiral template during the tandem reaction proceeds, the conformation of the Michael adducts (10-membered transition-state) was rather restricted to control the stereochemistry of the products. The reaction of, α,β-disubstituted vinyl phenyl ketone with (-)-10-mercaptoisobornenol afforded excellent results accompanying the stereoselective construction of three contiguous chiral carbons in the absence ofadditives. On the other hand, the range of the stereoselectivities of the reaction choosing α,β-disubstituted vinyl alkyl ketone as a substrate was potently affected by the pH values of additives. After being scrutinized many additives, pentafluorobenzoic acid (pKa 1.7) provided the best result to afford the high stereoselectivity. Furthermore, isoborneol moiety that is the chiral auxiliary in the reaction was removed by taking advantage of Wagner-Meerwein rearrangement to afford enatiomerically pure 1,3-mercapto alcohols with three contiguous chiral centers. Whisky lactones and cognac lactones were facilely prepared in optically pure form by using the tandem reaction mentioned above. In addition, we succeeded in preparing odorless thiols (Dodesyl-SH) and odorless sulfides (Dodesyl-S-Me), which carry 10 carbons as the alkyl chain, on the basis of the fact (-)-10-mercapto-isobornenol smells faint. Corey-Kim and Swern oxidations, dealkylation with AlCls-thiols combination, and reductive work up of ozonolysis became,attainable under odorless conditions by using the odorless reagents

本文报道了α，β-不饱和酮与手性巯基醇在串联Michael加成和Meerwein-Ponndorff-Verley（MPV）还原中高度立体选择性地构建三个连续的立体中心。在Me_2AlCl存在下，α，β-不饱和酮与（-）-10-巯基异冰片烯醇的反应，在Michael加成步骤中，α，β-不饱和酮在α-位发生不对称质子化，羰基发生1，1-氢化物位移还原。由于巯基醇在串联反应过程中起着手性模板的作用，因此Michael加成物（10元过渡态）的构象受到相当大的限制，以控制产物的立体化学。α，β-二取代乙烯基苯基酮与（-）-10-巯基异冰片烯醇的反应在无添加剂存在下得到了很好的结果，并伴有三个相邻手性碳的立体选择性构建。另一方面，添加剂的pH值对以α，β-二取代乙烯基烷基酮为底物的反应的立体选择性范围有很大的影响。在考察了多种添加剂后，五氟苯甲酸（pKa 1.7）提供了最好的结果，以提供高的立体选择性。此外，利用Wagner-Meerwein重排反应除去了反应中的手性助剂异冰片，得到了对映体纯的3个手性中心相连的1，3-巯基醇。利用上述串联反应，可方便地制备光学纯的威士忌内酯和干邑白兰地内酯。此外，我们成功地制备了无味的硫醇（十二烷基-SH）和无味的硫化物（十二烷基-S-Me），它们带有10个碳作为烷基链，基于（-）-10-巯基-异冰片烯醇气味微弱的事实。Corey-Kim和Swern氧化反应、AlCl 3-硫醇组合脱烷基反应以及臭氧分解的还原后处理在无臭条件下可通过使用无臭试剂来实现

项目成果

S.Ohsugi, K.Nishide, M.Node: "A novel tandem [4^++2] cycloaddition-elimination reaction : 2-alkenyl-4,4-dimethyl-1,3-oxathianes as synthetic equivalents for α,β-unsaturated thioaldehydes"Tetrahedron. 59. 1859-1871 (2003)

S.Ohsugi、K.Nishide、M.Node：“一种新型串联 [4^++2] 环加成消除反应：2-烯基-4,4-二甲基-1,3-氧杂硫烷作为 α,β 的合成等价物-不饱和硫醛”四面体。59。1859-1871（2003）

K.Nishide, M.Ozeki, H.Kunishige, Y.Shigeta, P.K.Patra, Y.Hagimoto, M.Node: "One-step stereocontrol of three contiguous stereogenic centers in acyclic system : The tuning effect of an additive in tandem Michael addition and MPV reduction."Angew.Chem.Int.Ed

K.Nishide、M.Ozeki、H.Kunishige、Y.Shigeta、P.K.Patra、Y.Hagimoto、M.Node：“非循环系统中三个连续立体中心的一步立体控制：串联迈克尔中添加剂的调谐效果

Manabu Node et al.: "A Novel asymmetric Tandem Michael Addition/Meerwein-Ponndorf-verley Reduction ; The highly Asymmetric Reduction of Acyclic α,β-Unsaturated Ketones to Secondary Alcohols and"J.Am.Chem.Soc.. 122. 1927-1936 (2000)

Manabu Node 等人：“新颖的不对称串联迈克尔加成/Meerwein-Ponndorf-verley 还原；无环 α,β-不饱和酮高度不对称还原为仲醇”和“J.Am.Chem.Soc.. 122. 1927 -1936 (2000)

M.Ozeki, K.Nishide, F.Teraoka, M.Node: "Diastereo-and enantioselective synthesis of anti-1,3-mercapto alcohols from α,β-unsaturated ketones via tandem Michael addition-MPV reduction"Tetrahedron Asymmetry. 15. 895-907 (2004)

M.Ozeki、K.Nishide、F.Teraoka、M.Node：“通过串联迈克尔加成 - MPV 还原从 α,β-不饱和酮非对映和对映选择性合成抗 1,3-巯基醇”四面体不对称性 15。 .895-907 (2004)

K.Nishide, S.Nishide, M.Fudesaka, S.Kodama, M.Node: "New odorless protocols for the Swern and Corey-Kim oxidations"Tetrahedron Lett.. 43. 5177-5179 (2002)

K.Nishide、S.Nishide、M.Fudesaka、S.Kodama、M.Node：“Swern 和 Corey-Kim 氧化的新无气味方案”Tetrahedron Lett.. 43. 5177-5179 (2002)