(R)-2,3-Cyclohexylideneglyceraldehyde: A Potential Intermediate for Convenient Synthesis of 2-C-Branched 2-Deoxypentofuranoses.
(R)-2,3-Cyclohexylideneglyceraldehyde: A Potential Intermediate for Convenient Synthesis of 2-C-Branched 2-Deoxypentofuranoses.
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(R)-2,3-亚环己基甘油醛：一种用于方便合成 2-C-支链 2-脱氧呋喃戊糖的潜在中间体。
DOI：
10.1021/jo982130k
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发表时间：
1999
影响因子：
3.6
通讯作者：
S. Hassarajani
中科院分区：
文献类型：
--
作者：
A. Chattopadhyay;B. Dhotare;S. Hassarajani
在过去的几十年里，简单或官能化有机金属与 R-和/或-烷氧基1或其他杂取代2羰基底物的C-C键形成亲核加成1-3立体控制引起了相当大的关注。所得的纯手性醇通常被用作通过凯龙方法合成光学纯化合物的结构单元。 4 因此，越来越需要在水性介质中进行此类有机金属化3，以期确定其实际可行性。同时，努力致力于理解和控制无环羰基有机金属化的立体选择性1-3，因为通过改变金属、溶剂、亲核体的立体化学等，存在获得此类加成的立体化学灵活性的可能性。虽然从合成的角度来看，羰基的高度立体选择性有机金属化总是令人期望的，但如果所有所得非对映醇都可以以纯形式从反应混合物中分离出来，则差或中等选择性的加成可能证明是有利的无需衍生化，因为这可能并不总是与后续反应方案兼容。在我们正在进行的生物活性化合物合成计划中，我们开发了 D-甘露醇来源的 1 的实用合成5a。我们发现 1 是 Zn 介导的 (E)-巴豆基化 5b 的良好底物，在 Luche 条件下有水存在时可产生 2、3 和 4。这些巴豆基化产物均具有三个连续的立体中心，其中两个是在有机金属化过程中产生的。值得一提的是，巴豆基金属化是传统羟醛缩合的有价值的替代品。然而，C-3 处甲基的存在阻止了该支化，需要进一步阐述。因此，为了引入羟甲基（C-3处最简单的官能化C支化取代甲基），按照与us5b先前所做的类似的程序，用溴化物7（1当量）和过量（2.5当量）的锌粉处理1，并发现在1.5小时内完全反应。化合物7由市售的(Z)-丁烯-1, 4-二醇(5)通过顺序单苄化和溴化制备，总产率可观。这也为我们提供了一个机会来比较手性 R-氧化醛（例如 1）在 Luche 条件下的 Zn 介导的 Barbier 型 (E)-和 (Z)-烯丙基金属化之间的立体选择。 6 据我们所知，这是此类研究的第一份报告。 1和7之间的反应具有高区域选择性，其中CC键的形成仅发生在γ位。这次，从 TLC 中可以明显看出，产物醇的所有四种可能的异构体 8-11 均已形成（方案 1）。然而，残余物的柱色谱法完全分离出10和11，并部分分离出所形成的9。发现一些初始级分含有8和9的混合物。根据柱色谱分离，估计8/9、10和11的形成比例为18.2:33.5:48.3。由于 8 的形成量可忽略不计且其 Rf 接近 9，因此尚未认真尝试通过柱色谱法分离它。纯形式的 9、10 和 11 的 1H NMR 谱显示，由于 H-4、H-5、H-6 和-CH2OBn，δ 3.5-4.2 区域中的信号具有明显的模式。 9 和 10 的立体化学可以通过分析其 1H NMR 光谱上述区域的信号来识别，这似乎与报道的 7 的信号非常相似……
StereocontrolinC-Cbondformingnucleophilicaddition1-3 of simple or functionalized organometallics to R-and/or-alkoxy1 or other heterosubstituted2 carbonyl substrates has drawn considerable attraction during the last few decades. The resulting homochiral alcohols are generally exploited as building blocks for the synthesis of optically pure compounds via a chiron approach. 4 Consequently, there has been an increasing demand to perform such organometalations in aqueous medium3 with a view to establishing their practical viability. Simultaneously, efforts are directed in understanding and controlling the stereoselectivity1-3 for the organometalations of acyclic carbonyls, as a possibility exists in attaining stereochemical flexibility for such additions by changing the metal, solvent, stereochemistry of the nucleophiles, etc. Although a highly stereoselective organometalation of a carbonyl is always desirable from a synthetic viewpoint, a poor or moderately selective addition may prove advantageous if all the resulting diastereo alcohols are isolable in pure form from the reaction mixture without being derivatized, as this may not always be compatible with subsequent reactions protocol. During our ongoing program on the synthesis of bioactive compounds, we have developed a practical synthesis5a of 1 of D-mannitol origin. We found 1 to be a good substrate for Zn-mediated (E)-crotylation5b in the presence of water under Luche’s condition6 to produce 2, 3, and 4. Each of these crotylation products has three contiguous stereocenters, two of which are generated during organometalation. It is worth mentioning that crotylmetalation is a valuable alternative to conventional aldol condensation. However, the presence of a methyl group at C-3 blocks that branching for further elaboration. Hence with a view to introducing a hydroxymethyl group, the simplest functionalized C-branching at C-3 in the place of the methyl group, 1 was treated with bromide 7 (1 equiv) and excess (2.5 equiv) of Zn dust following a procedure similar to one done previously by us5b and was found to be totally reacted within 1.5 h. Compound 7 was prepared from commercially available (Z)-buten-1, 4-diol (5) by sequential monobenzylation and bromination with an appreciable overall yield. This also provides us an opportunity to compare the stereoselection between Znmediated Barbier type (E)-and (Z)-allylmetalation of a chirally R-oxygenated aldehyde such as 1 under Luche’s condition. 6 To our knowledge, this constitutes the first report of this type of study. The reaction between 1 and 7 has been effected with high regioselectivity in which CC bond formation has exclusively taken place at the γ-position. This time the formation of all of the four possible isomers 8-11 of the product alcohol was evident from TLC (Scheme 1). However, column chromatography of the residue afforded total isolation of 10 and 11 and partial isolation of 9 that was formed. Some of the initial fractions were found to contain a mixture of 8 and 9. On the basis of column chromatographic isolation, the formation of 8/9, 10, and 11 has been estimated to be in the ratio of 18.2: 33.5: 48.3. Because of the formation of a negligible amount of 8 and its Rf close to that of 9, its isolation by column chromatography has not been attempted seriously. The 1H NMR spectra of 9, 10, and 11 available in pure form show distinguishable patterns of signals in the region of δ 3.5-4.2 due to H-4, H-5, H-6, and-CH2OBn. The stereochemistries of 9 and 10 could be identified by analyzing the signals in the aforementioned region of their 1H NMR spectra, which appear to be very much comparable with those of the reported ones7 for the …