Streamlined Catalytic Enantioselective Synthesis of α-Substituted β,γ-Unsaturated Ketones and Either of the Corresponding Tertiary Homoallylic Alcohol Diastereomers.
Streamlined Catalytic Enantioselective Synthesis of α-Substituted β,γ-Unsaturated Ketones and Either of the Corresponding Tertiary Homoallylic Alcohol Diastereomers.
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DOI：
10.1021/jacs.0c08732
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发表时间：
2020-10-21
影响因子：
15
通讯作者：
Hoveyda AH
中科院分区：
文献类型：
--
作者：
Pozo JD;Zhang S;Romiti F;Xu S;Conger RP;Hoveyda AH
公开了一种广泛适用、实用和可扩展的策略，用于含有α-立体中心的β，γ-不饱和酮的高效和对映选择性合成。因此，含有α-立体碳的芳基、杂芳基、炔基、烯基、烯基或烷基酮可以用现成的原料和市售的手性配体合成，产率为52-96%，对映体比为93:7至99:1。为了开发新方法，确定了具有高对映选择性的条件，并且得到的α-取代的nh -酮胺具有很强的C=N→B（pin）配位，在水解转化为衍生酮之前不会发生异构化。通过与烷基、芳基、杂芳基、烯丙基、乙烯基、炔基或丙炔金属试剂反应，酮类产品可以以70-96%的产率和92:8 ~ 98:2的非对映体形式转化为各种各样的均烯丙基叔醇。该方法的效用是通过提供其他所需衍生物的转化和简明的合成路线来突出的，这些合成路线提供了一克以上的抗艾滋病毒药物红氟二内酯a和B的主要片段以及特定的立体异构体类似物。
A widely applicable, practical, and scalable strategy for efficient and enantioselective synthesis of β,γ-unsaturated ketones that contain an α-stereogenic center is disclosed. Accordingly, aryl, heteroaryl, alkynyl, alkenyl, allyl, or alkyl ketones that contain an α-stereogenic carbon with an alkyl, an aryl, a benzyloxy, or a siloxy moiety can be generated from readily available starting materials and by the use of commercially available chiral ligands in 52–96% yield and 93:7 to >99:1 enantiomeric ratio. To develop the new method, conditions were identified so that high enantioselectivity would be attained and the resulting α-substituted NH-ketimines, wherein there is strong C=N→B(pin) coordination, would not epimerize before conversion to the derived ketone by hydrolysis. It is demonstrated that the ketone products can be converted to an assortment of homoallylic tertiary alcohols in 70–96% yield and 92:8 to >98:2 dr – in either diastereomeric form – by reactions with alkyl-, aryl-, heteroaryl-, allyl-, vinyl-, alkynyl-, or propargyl-metal reagents. The utility of the approach is highlighted through transformations that furnish other desirable derivatives and a concise synthesis route affording more than a gram of a major fragment of anti-HIV agents rubriflordilactones A and B and a specific stereoisomeric analogue.
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DOI：
10.1002/anie.201703079
发表时间：
2017-08-01
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Cano R;Zakarian A;McGlacken GP
通讯作者：
McGlacken GP
DOI：
10.1002/anie.201506366
发表时间：
2015-10-19
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
--
作者：
Goh SS;Chaubet G;Gockel B;Cordonnier MC;Baars H;Phillips AW;Anderson EA
通讯作者：
Anderson EA
影响因子：
16.6
作者：
Fujihara, Tetsuaki;Sawada, Ayumi;Tsuji, Yasushi
通讯作者：
Tsuji, Yasushi
DOI：
10.1002/chem.201502077
发表时间：
2015-10-12
期刊：
Chemistry (Weinheim an der Bergstrasse, Germany)
影响因子：
--
作者：
Bandyopadhyay A;Gao J
通讯作者：
Gao J
DOI：
10.1016/s0020-1693(00)88590-4
发表时间：
1981-01-01
期刊：
INORGANICA CHIMICA ACTA-ARTICLES
影响因子：
--
作者：
GULLIVER, DJ;LEVASON, W;WEBSTER, M
通讯作者：
WEBSTER, M