STEREOELECTRONIC CONTROL IN ENOLIZATION-KETONIZATION REACTIONS
STEREOELECTRONIC CONTROL IN ENOLIZATION-KETONIZATION REACTIONS
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DOI：
10.1021/ja01605a013
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发表时间：
1956-01-01
影响因子：
15
通讯作者：
SNEEN, RA
中科院分区：
文献类型：
--
作者：
COREY, EJ;SNEEN, RA
本文用氘示踪法研究了3/3-乙酰氧基胆甾烷-7-酮烯醇化为Δ 6-烯-7-醇和该烯醇酮化的立体化学。以溴化氢为催化剂，在氯仿溶液中，烯醇化反应中C6轴向氢的损失速度是赤道氢的1.2倍（经同位素效应校正），在逆反应酮化反应中，C6轴向氢的损失速度约为赤道氢的1.2倍。1.5是赤道氢气的两倍这些值，在理论上应该是相同的，是在合理的良好的协议，并表明，尽管一个强大的空间位阻的增益和损失的轴向氢，轴向攻击仍然是至少一样有利的赤道攻击。这种立体效应的校正给出的结果是，立体电子因素有利于轴向攻击赤道攻击至少12倍。乙酸催化的烯醇化-酮化反应甚至更特异，轴向攻击比赤道攻击更有利，总因子至少为9，立体电子分量至少为50。氘在7-甾酮烯醇化反应中的动力学同位素效应被发现是一个很好的例子。7.4，接近理论最大值10。本文从热力学角度解释了立体电子控制程度随试剂反应活性的变化，并从氯化和溴化实验的比较中引用了支持数据。甾体4，5，6-烯丙基阳离子反应中观察到的唯一轴向进攻被认为是高度立体电子控制的结果。以前的研究表明，甾体酮经相应烯醇的溴化反应在几种情况下，可能一般是通过将引入的溴取代基导向轴向而不是赤道位置的效应来表征的。与这种效应相反的是经典的空间效应，它将一个大的取代基（如溴）导向不那么拥挤的赤道方向。这两种影响轴向溴和赤道溴差向异构体形成的相对速率的效应的净结果在被分离的溴酮是不稳定差向异构体的情况下是清楚的，其形成是动力学的而不是稳态的原因。在这种情况下，非空间效应的重要性是显而易见的，因为主要产物总是被发现是轴向溴的差向异构体。[2]有人提出，导致这种立体化学优先性的取向影响是立体化学电子性质的，并取决于外环轨道α位的受扰轴键和赤道键中电子离域程度的差异。参考图1，表明立体化学取向与聚合程度之间的关系。
The stereochemistry of the enolization of 3/3-acetoxycholestan-7-oneto the A6-en-7-ol and of the ketonization of this enol have been studied using deuterium tracer. With hydrogen bromide as catalyst in chloroform solution the axial hydrogen at C6 is lost in enolization 1.2 times as rapidly as the equatorial hydrogen (corrected for isotope effect); for the reverse reac-tion, ketonization, an axial hydrogen is gained ca. 1.5 times as rapidly as an equatorial hydrogen. These values, which in theory should be identical, are in reasonably good agreement and indicate that despite a strong steric retardation of the gain and loss of an axial hydrogen, axial attack is still at least as favorable as equatorial attack. Correction for this steric effect gives the result that stereoelectronic factors favor axial attack over equatorial attack by a factor of at least 12. The acetic acid catalyzed enolization-ketonization reaction is even more specific and axial attack is favored over equatorial at-tack by a total factor of at least 9 with a stereoelectronic component of at least 50. The kinetic isotope effect of deuterium in enolization of 7-ketosteroids has been found to be ca. 7.4, close to the theoretical maximum at 10. A thermodynamic explanation is presented to explain the variation in degree of stereoelectroniccontrol with reactivity of the reagent andsup-porting data are cited from a comparison of chlorination and bromination experiments. The occurrence of a high degree of stereoelectronic control is postulated to explain the exclusive axial attack observed in reactions of steroidal 4, 5, 6-allyl cations.It has been shown previously2 that the bromination of steroid ketones via the corresponding enols is characterized in several cases, and perhaps gen-erally, by an effect which directs the incoming bromine substituent to the axial rather than the equa-torial position. Opposing this effectis the classical steric effect, which directs a large substituent such as bromine to the less crowded equatorial orientation. The net result ofthese two effects, which in-fluence therelative rates of formation of the epimers with axial and equatorial bromine, is clear in those cases where the bromoketone which is isolated is the unstable epimer, formed for kinetic rather than for steady-state reasons. In such instances the importance of the non-steric effectis apparent since the major product has invariably been found to be the epimer with axial bromine. 2 It has been proposed that the orienting influence which is responsible for this stereochemical pref-erence is stereochemical-electronicin nature and depends on the difference in degree of delocaliza-tion of electrons in perturbed axial and equatorial bonds which are alpha to an exocyclic-orbital. Reference to Fig. 1 indicates the relationship between stereochemical orientation and the extent of