Studies on Asymmetric Hydrogenation

由于现有的均相催化剂缺乏反应性和/或立体选择性，因此开发实用的方法来实现单酮的立体选择性加氢是非常必要的。具有反式-RuCl2(膦)2(1，2-二胺)或反式-RuCl2(双膦)(1，2-二胺)的新的Ru(II)配合物在含碱的2-丙醇中对多种单酮的加氢反应具有简便性。例如，底物/催化剂摩尔比为2,400,000的苯乙酮在30℃，45大气压下加氢得到1-苯乙醇。周转频率(TOF)，定义为每摩尔Ru催化剂每小时产物的摩尔，接近228,000。即使在常压氢气下，反应也能以合理的速度进行。这种混合配体催化剂在烯烃或内乙酰键存在的情况下，实现了羰基功能的化学选择性氢化。该反应使用庚醛和1-辛烯的等摩尔混合物，显示出高达1500的羰基/烯烃选择性。此外，具有碳*碳多键的各种酮和醛优先在羰基上氢化，从而产生不饱和醇。当Ru催化剂被2，2‘-二(二苯基膦)-1，1’-联萘(BINAP)和某些手性1，2-二胺(如1，2-二苯乙二胺和1-烷基-2，2-二(对甲氧基苯基)-1，2-乙二胺)修饰时，单酮的不对称加氢反应是可以实现的。在室温下，烷基芳基酮和直链α，β-不饱和酮在1-8atm的氢气中进行加氢反应，得到相应的手性醇，产率接近100%，Ee高达99%。由于催化剂的低成本、操作简单和环境意识，该过程特别适用于大规模反应。

The development of practical methods effecting stereoselective hydrogenation of simple ketones is highly desirable, since the existing homogeneous catalysts lack reactivity and/or stereoselectivity. New Ru (II) complexes having a formula of trans-RuCl_2 (phosphine) _2 (1,2-diamine) or trans-RuCl_2 (diphosphine) (1,2-diamine) in 2-propanol containing alkaline base effect facile hydrogenation of a wide variety of simple ketones. For example, hydrogenation of acetophenone with a substrate/catalyst molar ratio of 2,400,000 under 45 atm at 30'C gives 1-phenylethanol quantitatively. The turnover frequency (TOF), defined as the moles of product per mol Ru catalyst per hour, approaches 228,000. The reaction proceeds at a reasonable rate even under atmospheric pressure of hydrogen.This mixed-ligand catalyst effects chemoselective hydrogenation of a carbonyl function in the presence of an olefinic or internal acetylenic bond. The reaction using an equimolar mixture of heptanal and 1-octene displays a carbonyl/olefin selectivity as high as 1500. Furthermore, a wide range of ketones and aldehydes possessing a carbon*carbon multiple bond are hydrogenated preferentially at the carbonyl group, leading to unsaturated alcohols. Both conjugated and unconjugated enals or enones can be used.Highly enantioselective hydrogenation of simple ketones is achievable when the Ru catalyst is modified by 2,2'-bis (diphenylphosphino)-1,1'-binaphthyl (BINAP) and certain chiral 1,2-diamines such as 1,2-diphenylethylenediamine and 1-alkyl-2,2-bis (p-methoxyphenyl)-1,2-ethylenediamine. The hydrogenation of alkyl aryl ketones and linear alpha, beta-unsaturated ketones under 1-8 atm of H_2 at room temperature affords the corresponding chiral alcohols in near 100% yield and in up to 99% ee.This procedure is particularly useful for a large-scale reaction because of the low cost of the catalyst, operational simplicity, and environmental consciousness.