Asymmetric Synthesis of Densely Functionalized Medium-Ring Carbocycles and Lactones through Modular Assembly and Ring-Closing Metathesis of Sulfoximine-Substituted Trienes and Dienynes

被引：17

作者：

Lejkowski, Michal ^{[1
]}

Banerjee, Prabal ^{[1
]}

Schueller, Sabine ^{[1
]}

Muench, Alexander ^{[1
]}

Runsink, Jan ^{[1
]}

Vermeeren, Cornelia ^{[1
]}

Gais, Hans-Joachim ^{[1
]}

机构：

[1] Rhein Westfal TH Aachen, Inst Organ Chem, D-52074 Aachen, Germany

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2012年 / 18卷 / 12期

关键词：

carbocycles; lactones; medium-sized rings; ring-closing metathesis; sulfoximines; MEDIUM-SIZED CARBOCYCLES; METALATED ALKENYL SULFOXIMINES; CATALYZED OLEFIN METATHESIS; CROSS-COUPLING REACTIONS; FORMAL TOTAL-SYNTHESIS; ALPHA-AMINO-ACIDS; ENYNE METATHESIS; RUTHENIUM CARBENE; NATURAL-PRODUCTS; ENANTIOSELECTIVE SUBSTITUTION;

D O I：

10.1002/chem.201103060

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

An asymmetric synthesis of densely functionalized 711-membered carbocycles and 911-membered lactones has been developed. Its key steps are a modular assembly of sulfoximine-substituted C- and O-tethered trienes and C-tethered dienynes and their Ru-catalyzed ring-closing diene and enyne metathesis (RCDEM and RCEYM). The synthesis of the C-tethered trienes and dienynes includes the following steps: 1) hydroxyalkylation of enantiomerically pure titanated allylic sulfoximines with unsaturated aldehydes, 2) a-lithiation of alkenylsulfoximines, 3) alkylation, hydroxy-alkylation, formylation, and acylation of a-lithioalkenylsulfoximines, and 4) addition of Grignard reagents to a-formyl(acyl)alkenylsulfoximines. The sulfoximine group provided for high asymmetric induction in steps 1) and 4). RCDEM of the sulfoximine-substituted trienes with the second-generation Ru catalyst stereoselectively afforded the corresponding functionalized 711-membered carbocyles. RCDEM of diastereomeric silyloxy-substituted 1,6,12-trienes revealed an interesting difference in reactivity. While the (R)-diastereomer gave the 11-membered carbocyle, the (S)-diastereomer delivered in a cascade of cross metathesis and RCDEM 22-membered macrocycles. RCDEM of cyclic trienes furnished bicyclic carbocycles with a bicyclo[7.4.0]tridecane and bicyclo[9.4.0]pentadecane skeleton. Selective transformations of the sulfoximine- and bissilyloxy-substituted carbocycles were performed including deprotection, cross-coupling reaction and reduction of the sulfoximine moiety. Esterification of a sulfoximine-substituted homoallylic alcohol with unsaturated carboxylic acids gave the O-tethered trienes, RCDEM of which yielded the sulfoximine-substituted 911-membered lactones. RCEYM of a sulfoximine-substituted 1,7-dien-10-yne showed an unprecedented dichotomy in ring formation depending on the Ru catalyst. While the second-generation Ru catalyst gave the 9-membered exo 1,3-dienyl carbocycle, the first-generation Ru catalyst furnished a truncated 9-membered 1,3-dieny carbocycle having one CH2 unit less than the dienyne.

引用

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页码：3529 / 3548

页数：20

共 42 条

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