Optical Rotatory Dispersion Studies. XC.1 The Octant Rule and the Isopropyl Group. Synthesis of Steroidal Isopropyl Ketones2
Optical Rotatory Dispersion Studies. XC.1 The Octant Rule and the Isopropyl Group. Synthesis of Steroidal Isopropyl Ketones2
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旋光色散研究。
DOI：
10.1021/ja01055a020
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发表时间：
1964
影响因子：
15
通讯作者：
C. Beard
中科院分区：
文献类型：
--
作者：
C. Djerassi;P. A. Hart;C. Beard
为了获得环己酮中与羰基相邻的赤道或轴向异丙基的旋光色散幅度贡献的标准值，合成了2 α-和2/3-异丙基胆甾烷-3-酮、2 α-和2/3-异丙基-19-去甲-5 α-雄甾烷-3-酮以及光学纯的2-异丙基环己酮。对这些振幅值和由（-）-薄荷酮和（+）-异薄荷酮得到的振幅值的考虑证实了早先的结论，即轴向和赤道向α-异丙基环己酮之间的能量差小于1千卡。鼹鼠在对2-异丙基环己酮和（+）-异薄荷酮构象情况的讨论中，进一步证明了这种振幅值在构象分析中的实用性，并指出了在构象分析中获得可靠的环己酮环上羰基邻位取代基的Cotton效应振幅贡献值的重要性。[1]关于甲基4和（-丁基1）取代基的实验和结论已经有了记录，现在我们要描述关于异丙基的类似研究。这个取代基是特别令人感兴趣的，因为它是在天然存在的萜烯中频繁发现的，并且在将八分体规则应用于此类酮时，对该基团的旋光贡献的适当评估是必不可少的。6因此，在对（-）-薄荷酮（IV）8和（+）-异薄荷酮（V）8的旋光色散曲线的初步评估中，得出了当时未预料到的结论，即（+）-异薄荷酮（V）主要以异丙基为轴向的构象Va而不是先验预期的Vb存在。这一结论在Allinger 9和Rickborn 4最近的研究中得到了证实。为了得到关于异丙基取代基所起的旋转和构象作用的更详细的信息，需要最简单的光学活性2-异丙基-环己酮（III）-以及其他对差向异构-异丙基环己酮（类似于IV和V）。正如在（-丁基系列，1类固醇似乎代表令人钦佩的例子，我们报告
In order to obtain standard values for the rotatory dispersion amplitude contribution of an equatorial or axial isopropyl group adjacent to a carbonyl group in a cyclohexanone, 2a-and 2/3-isopropylcholestan-3-one, 2a-and 2/3-isopropyl-19-nor-5a-androstan-3-one, and optically pure 2-isopropylcyclohexanone were synthesized. Consideration ofthese amplitude values and those derived from (—)-menthone and (+)-isomenthone confirm the earlier conclusion that the energy difference between an axial and an equatorial a-isopropylcyclohexanone is less than 1 kcal./molé. The utility of such amplitude values in conformational analysis is demonstrated further in a discussion of the conformational situation existing in 2-isopropylcyclohexanone and (+)-isomenthone.The importance in conformational analysis of ob-taining reliable values for the Cotton effectamplitude contribution of substituents adjacent to a carbonyl group in a cyclohexanone ring has already been pointed out in the preceding article. 1 Experiments and con-clusions dealing with methyl4 and (-butyl1 substituents have been recorded and we should now like to describe similar studies with the isopropyl group. This sub-stituent is of particular interest, since it is found fre-quently among naturally occurring terpenes and a proper evaluation of the rotatory contribution of this group is indispensable in applications of the octant rule5 to such ketones. 6 Thus in a preliminary evaluation7 of the optical rotatory dispersion curves of (—)-menthone (IV) 8 and (+)-isomenthone (V), 8 the then un-expected conclusion was reached that (+)-isomenthone (V) existed largely in the conformation Va in which the isopropyl group is axial rather than the a priori anticipated Vb. This conclusion was substantiated in recent studies by Allinger9 and Rickborn 4 In order to get more detailed information on the rotational and conformational role played by an isopropyl substituent, the simplestmember—optically active 2-isopropyl-cyclohexanone (III)—as well as other pairs of epimeric-isopropylcyclohexanones (analogousto IV and V) were required. Just as in the (-butyl series, 1 steroids seemed to represent admirable examples and we report