A green chemistry approach to a more efficient asymmetric catalyst: Solvent-free and highly concentrated alkyl additions to ketones
A green chemistry approach to a more efficient asymmetric catalyst: Solvent-free and highly concentrated alkyl additions to ketones
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DOI：
10.1021/ja052200m
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发表时间：
2005-11-30
影响因子：
15
通讯作者：
Walsh, PJ
中科院分区：
文献类型：
--
作者：
Jeon, SJ;Li, HM;Walsh, PJ
存在对开发不仅高效和高对映选择性而且环境友好的催化剂体系的巨大需求。本文报道了在高浓度和无溶剂条件下烷基和官能化烷基对酮的催化不对称加成反应。与使用甲苯和己烷的标准反应条件相比，无溶剂和高度浓缩的条件允许催化剂负载减少2- 40倍。这些新的条件是通用的，并适用于各种酮和二烷基锌试剂，以提供不同的叔醇具有高的对映选择性。使用环状共轭烯酮，我们已经进行了串联的不对称加成/clistereoselective环氧化反应，使用无溶剂的加成条件，然后引入5.5 M癸烷溶液的叔丁基过氧化氢（TBHP），以产生环氧醇。这种一锅法允许获得具有三个连续立构中心的顺式环氧醇，具有优异的对映体和非对映体选择性和高产率。无溶剂的不对称加成和不对称加成/对映选择性环氧化反应都已在较大规模（5g底物）上以0.5mol%催化剂负载量进行。在这些程序中，对映体选择性等于或优于92%，得到的分离产率为90%。无溶剂和高度浓缩的条件是对以前基于溶剂的方案的显著改进。此外，这种化学反应代表了催化不对称反应的一个罕见的例子，它在更环保的无溶剂条件下具有高度的对映选择性。
There is a great demand for development of catalyst systems that are not only efficient and highly enantioselective but are also environmentally benign. Herein we report investigations into the catalytic asymmetric addition of alkyl and functionalized alkyl groups to ketones under highly concentrated and solvent-free conditions. In comparison with standard reaction conditions employing toluene and hexanes, the solvent-free and highly concentrated conditions permit reduction in catalyst loading by a factor of 2- to 40-fold. These new conditions are general and applicable to a variety of ketones and dialkylzinc reagents to provide diverse tertiary alcohols with high enantioselectivities. Using cyclic conjugated enones, we have performed a tandem asymmetric addition/cliastereoselective epoxidation using the solvent-free addition conditions followed by introduction of a 5.5 M decane solution of tert-butyl hydroperoxide (TBHP) to generate epoxy alcohols. This one-pot procedure allows access to syn epoxy alcohols with three contiguous stereocenters with excellent enantio- and diastereoselectivities and high yields. Both the solvent-free asymmetric additions and asymmetric addition/cliastereoselective epoxidation reactions have been conducted on larger scale (5 g substrate) with 0.5 mol % catalyst loadings. In these procedures, enantioselectivities equal to or better than 92% were obtained with isolated yields of 90%. The solvent-free and highly concentrated conditions are a significant improvement over previous solvent-based protocols. Further, this chemistry represents a rare example of a catalytic asymmetric reaction that is highly enantioselective under more environmentally friendly solvent-free conditions.