Asymmetric synthesis of α-substituted allyl boranes and their application in the synthesis of iso-agatharesinol
Asymmetric synthesis of α-substituted allyl boranes and their application in the synthesis of iso-agatharesinol
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DOI：
10.1002/anie.200603659
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发表时间：
2007-01-01
影响因子：
16.6
通讯作者：
Aggarwal, Varinder K.
中科院分区：
文献类型：
--
作者：
Fang, Guang Yu;Aggarwal, Varinder K.
手性烯丙基硼试剂与醛的反应已经并将继续在复杂天然产物的不对称合成中发挥重要作用尽管α-取代的烯丙基硼试剂经常与几乎完全立体感应的醛反应，但这类试剂并没有享受到相同的轮廓，可能是因为它们的不对称合成不太容易。然而，许多方法已经描述了α-取代丙烯基硼酸盐在对映体富集形式的合成。[2-5]然而，更活泼的α-取代烯丙基硼烷的合成被证明是难以实现的：唯一报道的例子是由环1,3 -二烯的不对称硼氢化而得到的本文描述了一种合成具有很高对映选择性的α-取代烯丙基硼烷的简单方法，并证明了其在合成中的实用性。我们最近描述了手性硫酰化物与对称硼烷的反应，硼烷氧化后生成具有很高对映选择性的仲醇本研究提出了一种合成α取代烯丙基硼烷的方法：手性硫酰基与乙烯基硼烷的反应。取代的9-硼比环-[3.3][1]壬烷（9-BBN）很容易通过末端炔与9-BBN的区域选择性硼化反应得到。然而，在不对称硼烷与硫酰基的反应中，不同基团的迁移能力问题必须加以解决虽然乙烯基被认为是一个比硼环更好的迁移基团，但结果并不清楚，因为我们已经在b -苯基-9- bbn与衍生自1的乙基的反应中经历了惊喜，我们发现了硼环的竞争性迁移在此情况下，由1衍生的乙基醚在À1008C与乙烯基硼烷2a反应，然后在相同温度下加入PhCHO，以96%的收率得到了纯烯丙醇5a，作为具有高Z选择性的单一非对映体（程序a，方案1）。获得的高产量清楚地表明乙烯基是排他性迁移的。我们还发现，将丙烯硼烷3a加热至08℃可异构化为4a，再冷却至À788C并与苯甲醛捕获后，产生另一种具有同样高非对映选择性的同丙烯醇6a（程序B，方案1）。我们使用手性磺酸盐（表1）对一系列乙烯基硼烷进行了步骤A，该盐先前用于硼烷与硫酰、[7]环氧化、[12]和其他相关反应的高度对映选择性反应在所有情况下，我们观察到基本上完全的对映体选择性和非对映体选择性，具有非常高的Z选择性。
The reaction of chiral allyl boron reagents with aldehydes has played and continues to play a major role in the asymmetric synthesis of complex natural products.[1] Despite the fact that α-substituted allyl boron reagents often react with aldehydes with almost complete stereoinduction, such reagents have not enjoyed the same profile, possibly because their asymmetric synthesis is less facile. Nevertheless, a number of methods have been described for the synthesis of α-substituted allyl borates in enantiomerically enriched form.[2–5] However, the synthesis of the more reactive α-substituted allyl boranes has proved elusive: the only examples that have been reported are those derived from the asymmetric hydroboration of cyclic 1, 3-dienes.[6] Herein we describe a simple procedure for the synthesis of α-substituted allyl boranes with very high enantioselectivity and demonstrate their utility in synthesis. We recently described the reaction of chiral sulfur ylides with symmetrical boranes which after oxidation furnished secondary alcohols with very high enantioselectivity.[7] This study suggested to us a potential solution to the synthesis of αsubstituted allyl boranes: the reaction of chiral sulfur ylides with vinyl boranes. Substituted vinyl 9-borabicyclo-[3.3. 1] nonanes (9-BBNs) are easily obtained by regioselective hydroboration of terminal alkynes with 9-BBN. However, in the reaction of nonsymmetrical boranes with sulfur ylides, issues of migration ability of the different groups have to be addressed.[8] Although the vinyl group is expected to be a better migrating group than the boracycle,[9] the outcome was not clear, as we had already experienced surprises in the reaction of B-phenyl-9-BBN with the ylide derived from 1, in which we found competing migration of the boracycle.[10] In the event, reaction of the ylide derived from 1 with vinylborane 2a at À1008C followed by addition of PhCHO at the same temperature furnished the homoallylic alcohol 5a in 96% yield as a single diastereomer with high Z selectivity (procedure A, Scheme 1). The high yield obtained clearly indicated that the vinyl group migrated exclusively. We also found that warming allylborane 3a to 08C resulted in isomerization to 4a, which upon recooling to À788C and trapping with benzaldehyde furnished another homoallylic alcohol 6a with similarly high diastereoselectivity (procedure B, Scheme 1).We applied procedure A to a range of vinyl boranes using the chiral sulfonium salt 7 [11](Table 1) that had previously been used in highly enantioselective reactions between boranes and sulfur ylides,[7] epoxidations,[12] and other related reactions.[13] In all cases, we observed essentially complete enantio-and diastereoselectivity with very high Z selectivity.