LITHIUM TRI-SEC-BUTYLBOROHYDRIDE - NEW REAGENT FOR REDUCTION OF CYCLIC AND BICYCLIC KETONES WITH SUPER STEREOSELECTIVITY - REMARKABLY SIMPLE AND PRACTICAL PROCEDURE FOR CONVERSION OF KETONES TO ALCOHOLS IN EXCEPTIONALLY HIGH STEREOCHEMICAL PURITY
LITHIUM TRI-SEC-BUTYLBOROHYDRIDE - NEW REAGENT FOR REDUCTION OF CYCLIC AND BICYCLIC KETONES WITH SUPER STEREOSELECTIVITY - REMARKABLY SIMPLE AND PRACTICAL PROCEDURE FOR CONVERSION OF KETONES TO ALCOHOLS IN EXCEPTIONALLY HIGH STEREOCHEMICAL PURITY
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DOI：
10.1021/ja00775a053
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发表时间：
1972-01-01
影响因子：
15
通讯作者：
KRISHNAMURTHY, S
中科院分区：
文献类型：
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作者：
BROWN, HC;KRISHNAMURTHY, S
先生道：在室温下，将1摩尔当量的三仲丁基硼烷加入到三甲氧基铝氢化锂（LTMA）的四氢呋喃（THF）溶液中，导致容易且快速地置换甲醇铝，以定量产率产生新试剂三仲丁基硼氢化锂。这种高度受阻的三烷基硼氢化锂是第一种被报道的试剂，是一种活性还原剂，在环状和双环酮的还原中表现出基本上类似酶的立体选择性。因此，即使是具有相对远离反应中心的烷基的酮，例如3-甲基-和4-正丁基-环己酮，也以> 95%的立体选择性降低，产生较不稳定的差向异构体。这似乎是第一个亲核试剂能够还原这样的环状酮具有如此高的立体选择性。1受阻酮，如2-甲基环己酮、3，3，5-三甲基环己酮、樟脑等，使用这种新试剂可以快速定量地减少，对相应的不太稳定的异构体具有超过99.5%的立体选择性。因此，锂三甲氧基铝氢化物-三仲丁基硼烷组合提供了一种新的简单实用的方法，用于酮转化为醇，实现了最高的立体专一性。我们最近证实，锂全氢-9bboraphenalylhydride（PBPH），由cis，cis，-Irans-perhydro-9 b-boraphenalene和氢化锂制备，还原环状和双环酮具有高立体选择性，快速和定量。[2]从那时起，这种新试剂和相关的三烷基硼烷被广泛地用于酮的立体选择性还原为醇官能团，包括在三尖杉酯碱合成中的两个主要应用，其中使用所有其他以前已知的试剂都失败了。3-5似乎更受阻的三烷基硼氢化物可能会改善立体选择性。不幸的是，我们遇到了一个重大的合成困难。更受阻的三烷基硼烷不能以任何明显的速率与氢化锂在THF中反应。因此，三乙基-、三-丁基-和三异丁基硼烷与氢化锂在THF中的反应快速且定量地进行，而氢化锂在THF中的反应在THF中进行。
Sir: Addition of 1 mol equiv of tri-sec-butylborane to a tetrahydrofuran (THF) solution of lithium trimethoxyaluminohydride (LTMA) at room temperature results in a facile and rapid displacement of aluminum meth-oxide, producing the new reagent, lithium tri-sec-butylborohydride, in quantitative yield. This highly hindered lithium trialkylborohydride, first reagent of its kind to be reported, is an active reducing agent and exhibits essentially enzyme-like stereoselectivity in the reduction of cyclic and bicyclic ketones. Thus even ketones with an alkyl group relatively remote from the reaction center, such as 3-methyl-and 4-/cr/-butyl-cyclohexanone, are reduced in> 95% stereoselectivity, producing the less stable epimer. This appears to be the first nucleophilic reagent capable of reducing such cyclic ketones with such high stereoselectivity. 1 Hin-dered ketones, such as 2-methylcyclohexanone, 3, 3, 5-trimethylcyclohexanone, camphor, etc., are reduced rapidly and quantitatively with this new reagent with over 99.5% stereoselectivity to the corresponding less stable isomers. Thus, the lithium trimethoxyalumino-hydride-tri-sec-butylborane combination provides a new simple practical procedure for the conversion of ketones to alcohols with the highest stereospecificity realized.We recently reportedthat lithium perhydro-9bboraphenalylhydride (PBPH), prepared from cis, cis,-Irans-perhydro-9b-boraphenalene and lithium hydride, reduces cyclic and bicyclic ketones with high stereo-selectivity, rapidly and quantitatively. 2 Since thenthis new reagent and related trialkylborohydrides have been used extensively for the stereoselective reduction of ketones to the alcoholfunction, including two major applications in thesynthesis of prostaglandins, where the use of all other previously known reagents had failed. 3-5 It appeared possible that a more hindered trialkyl-borohydride might improve the stereoselectivity. Unfortunately, we encountered a major synthetic difficulty. The more hindered trialkylboranes failed to react at any appreciable rate with lithium hydride in THF. Thus, the reactions oftriethyl-, tri-71-butyl-, and tri-isobutylboranes proceeded rapidly and quantitatively with lithium hydride in refluxing THF, whereas the