Ruthenium Catalyzed Diastereo- and Enantioselective Coupling of Propargyl Ethers with Alcohols: Siloxy-Crotylation via Hydride Shift Enabled Conversion of Alkynes to π-Allyls.
Ruthenium Catalyzed Diastereo- and Enantioselective Coupling of Propargyl Ethers with Alcohols: Siloxy-Crotylation via Hydride Shift Enabled Conversion of Alkynes to π-Allyls.
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DOI：
10.1021/jacs.5b08019
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发表时间：
2015-10-14
影响因子：
15
通讯作者：
Krische MJ
中科院分区：
文献类型：
--
作者：
Liang T;Zhang W;Chen TY;Nguyen KD;Krische MJ
首次报道了直接使用炔作为手性烯丙基金属等价物的不对称羰基巴豆酰化反应。Josiphos修饰的手性钌（II）配合物（SL-J 009 -1）催化TIPS保护的炔丙基醚1a与伯醇2a-2 o的C-C偶联以形成羰基炔丙基-巴豆酰化产物3a-3 o，其在甲硅烷基脱保护-还原后以优异的区域-、反-非对映-和对映选择性控制得到1，4-二醇5a-5 o。结构相关的炔丙基醚1b和1c轴承乙基和苯基取代基从事非对映和对映选择性耦合，如所示的形成加合物5 p和5 q，分别。二醇5a、5c、5e、5 f、5 k和5 m的选择性单甲苯磺酰化伴随着自发环化以分别提供反式-2，3-二取代的呋喃6a、6c、6 e、6 f、6 k和6 m。伯醇2a、2l和2 p转化为甲硅烷基-巴豆酰化产物3a、3l和3 p，这些产物在甲硅烷基脱保护-内半乳醇氧化后转化为反式-4，5-二取代γ-丁内酯7a、7 l和7 p。7 p的形成代表（+）-trans-whisky内酯的全合成。与密切相关的钌催化的炔-醇C-C偶联不同，氘标记研究提供了新的1，2-氢化物移位机制的明确证据，该机制在没有插入联烯的情况下将金属结合的炔转化为π-烯丙基。
The first enantioselective carbonyl crotylations through direct use of alkynes as chiral allylmetal equivalents are described. Chiral ruthenium(II) complexes modified by Josiphos (SL-J009-1) catalyze the C-C coupling of TIPS-protected propargyl ether 1a with primary alcohols 2a-2o to form products of carbonyl siloxy-crotylation 3a-3o, which upon silyl deprotection-reduction deliver 1,4-diols 5a-5o with excellent control of regio-, anti-diastereo- and enantioselectivity. Structurally related propargyl ethers 1b and 1c bearing ethyl- and phenyl-substituents engage in diastereo- and enantioselective coupling, as illustrated in the formation of adducts 5p and 5q, respectively. Selective mono-tosylation of diols 5a, 5c, 5e, 5f, 5k and 5m is accompanied by spontaneous cyclization to deliver the trans-2,3-disubstituted furans 6a, 6c, 6e, 6f, 6k and 6m, respectively. Primary alcohols 2a, 2l and 2p were converted to the siloxy-crotylation products 3a, 3l and 3p, which upon silyl deprotection-lactol oxidation were transformed to the trans-4,5-disubstituted γ-butyrolactones 7a, 7l and 7p. The formation of 7p represents a total synthesis of (+)-trans-whisky lactone. Unlike closely related ruthenium catalyzed alkyne-alcohol C-C couplings, deuterium labeling studies provide clear evidence of a novel 1,2-hydride shift mechanism that converts metal-bound alkynes to π-allyls in the absence of intervening allenes.