REDUCTION OF DELTA-2-ISOXAZOLINES .3. RANEY-NICKEL CATALYZED FORMATION OF BETA-HYDROXY KETONES
REDUCTION OF DELTA-2-ISOXAZOLINES .3. RANEY-NICKEL CATALYZED FORMATION OF BETA-HYDROXY KETONES
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DOI：
10.1021/ja00356a021
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发表时间：
1983-01-01
影响因子：
15
通讯作者：
CURRAN, DP
中科院分区：
文献类型：
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作者：
CURRAN, DP
0-羟基酮部分的重要性导致了用于其构建的各种各样的羟醛类型方法的发展。本文提出了一种新的合成“羟醛加合物”的方法，即通过原位生成的氧化腈和烯烃的[3+ 2]偶极环加成反应，然后还原生成的A2-异恶唑啉。这种方法为羟醛型反应提供了很好的补充。A2-异恶唑啉转化为O-羟基酮的最佳条件是使用Raney镍催化剂、硼酸、5/1 MeOH/H2O和氢气。在这些温和的条件下，3-甲基-5-正丁基-Δ 2-异恶唑啉（3a）以高产率转化为4-羟基-2-辛酮（4a）。因此，通过选择合适的烯烃和腈氧化物前体（通常为硝基化合物），可以容易地获得“定向羟醛”型加合物。优点在于前体的易得性、反应条件的温和性、高度的化学选择性和与许多官能团的相容性，以及在立体选择性和新碳-碳键的位置方面与羟醛型反应的一般互补性。最重要的是，环加成-还原序列允许三个和三个产物的非对映体特异性形成的独特可能性。例如，甲基腈氧化物与反式-2-丁烯的环加成得到反式取代的异恶唑啉8 t，其被还原以仅得到苏型0-羟基酮9 t。相反，使用顺式-2-丁烯在还原时得到异恶唑啉8 c和顺式异构体9 e。在此，发现添加剂的性质对于防止差向异构化是最关键的。这一方法将极大地拓展A_2-异恶唑啉在有机合成中的应用。羟醛缩合反应及相关的羰基加成和缩合反应在有机化学中具有重要意义。在过去的几年里，羟醛型加成反应领域的研究并没有减少，事实上，已经大大增加了。这部分是由于大量重要的天然产物含有O-羟基羰基单元。从合成策略的观点来看，绝大多数的0-羟基酮是通过羰基加成作为关键的碳-碳-碳键形成反应来构建的。因此，人们认识到，形成0-羟基酮的一系列令人印象深刻的优雅方法主要来自羰基加成的这一基本概念。4显然，需要开发其他根本不同的策略，这些策略可能有望补充羟醛型反应。这样的策略可能在复杂的天然产物中具有巨大的应用潜力
The importance of the 0-hydroxy ketone moiety has led to the development of a wide variety of aldol type methodologies for its construction. A conceptually new approach to these “aldol adducts” is presented on the basis of [3+ 2] dipolar cycloaddition of in situ generated nitrile oxides and olefins followed by reductionof the resulting A2-isoxazoIines. This approach provides a nice complement to the aldol type reaction. Optimum conditions for the transformationof A2-isoxazolines to 0-hydroxy ketones use Raney-nickel catalyst, boric acid, 5/1 MeOH/H20, and hydrogen gas. Under these mild conditions, 3-methyl-5-n-butyl-A2-isoxazoline (3a) is transformed to 4-hydroxy-2-octanone (4a) in high yield. Thus “directed aldol” type adducts are readily available by selection of the appropriate olefin and nitrile oxide precursor (usually the Io nitro compound). Advantages lie in the ready availability of precursors, the mildness of reaction conditions, the high degree of chemoselectivity and compatibility with many functional groups, and the general complimentarity to the aldol type reaction with regards to stereoselectivity and location of the new carbon-carbon bond. Most importantly, the cycloaddition-reduction sequence allows the unique possibility for diastereospecific formationof three and erythro products. For example, cycloaddition of methylnitrile oxide with iraŦs-2-butene gives the trans-substituted isoxazoline 8t, which is reduced to give exclusively the threo 0-hydroxy ketone 9t. In contrast, use of c/s-2-butene gives isoxazoline 8c and the erythro isomer 9e upon reduction. Here the nature of the additive was found to be most critical to prevent epimerization. It is expected that this approach will greatly expand the utility of A2-isoxazolines in organic synthesis.The aldol and related carbonyl addition and condensation re-actions are of fundamentalimportance in organic chemistry. 3 Over the past several years, research in the area of aldol type addition reactions has not waned but, in fact, has dramatically increased. This is due inpart to the large number of important natural products containing the 0-hydroxy carbonyl unit. From the standpoint of synthetic strategy, the vast majority of 0-hydroxy ketones are constructed by a carbonyl addition as the key car-bon-carbon bond-forming reaction. As such, it is realized that the impressive arrayof elegant methods for formation of 0-hydroxy ketones emanate largely from this singlebasic concept of carbonyl addition. 4 Clearly it would be desirable to develop other fundamentally different strategies that might be expected to com-plement the aldol type reaction. Such strategies might then have tremendous potential for applications in complex natural product