Concerning the synthesis of the elusive anti,anti-dipropionate stereotriad via the crotylation of β-hydroxy α-methyl aldehydes with (Z)-crotyltrifluorosilane.: Application to the synthesis of the C(7)-C(16) segment of zincophorin
Concerning the synthesis of the elusive anti,anti-dipropionate stereotriad via the crotylation of β-hydroxy α-methyl aldehydes with (Z)-crotyltrifluorosilane.: Application to the synthesis of the C(7)-C(16) segment of zincophorin
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DOI：
10.1021/jo980387c
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发表时间：
1998-06-12
影响因子：
3.6
通讯作者：
Roush, WR
中科院分区：
文献类型：
--
作者：
Chemler, SR;Roush, WR
抗、抗二丙酸立体三联体3是聚酮类天然产物中常见的一种亚基，通常被认为很难合成。2，3通过羟醛或巴豆基金属化方案选择性地合成这种立体三元化合物本身是有问题的，因为它必须产生于不受欢迎的过渡态，4，5其中试剂以反Felkin的方式添加到手性醛中(如下所示，用于1与类型1巴豆基金属试剂的反应)。6原则上以1为原料，在错配的双不对称反应中使用手性试剂可直接合成二丙酸酯3。Masamune7和Hoffmann8分别开发了高对映体选择性的烯醇硼酸酯和巴豆基硼酸酯试剂，并在挑战错配的双对称反应中实现了对反、反二丙酸酯的高选择性。然而，Masamune和Hoffmann试剂需要几个步骤来准备。此外，Marshall9和Panek10已经证明，手性烯基锡烷和克辛基硅烷试剂与R-甲基-β-苯甲氧基取代醛的络合控制加成选择性地提供了抗、抗二丙酸3。在这里，马歇尔试剂和帕内克试剂也需要多步准备。综述了合成抗、抗二丙酸立体三联体的其他策略。3我们报道了R-甲基β-羟基醛与(Z)-巴豆基三氟硅烷(5，11)的巴曲化反应，以2，3-反β-羟基R-甲基醛为起始原料，得到了具有良好选择性的反，反二丙酸7。我们也报告了这种方法的应用。
The anti, anti-dipropionate stereotriad 3, a common subunit found in polyketide-derived natural products, has generally been acknowledged as difficult to synthesize. 2, 3 The selective synthesis of this stereotriad by way of aldol or crotylmetalation protocols is inherently problematic as it must arise from a disfavored transition state, 4, 5 where the reagent adds to the chiral aldehyde in an anti-Felkin manner (illustrated below for the reaction of 1 with a type 1 crotylmetal reagent). 6In principle, dipropionate 3 can be prepared directly from 1 by using chiral reagents in mismatched double-asymmetric reactions. Masamune7 and Hoffmann8 have developed highly enantioselective enol boronate and crotylboronate reagents, respectively, and have achieved high selectivity for the anti, anti-dipropionate in challenging mismatched doubleasymmetric reactions. However, the Masamune and Hoffmann reagents require several steps to prepare. Additionally, Marshall9 and Panek10 have demonstrated that chelatecontrolled addition of chiral allenylstannane and crotylsilane reagents to R-methyl-β-benzyloxy-substituted aldehydes provide anti, anti-dipropionate 3 selectively. Here also, the Marshall and Panek reagents require multistep preparations. Other strategies for the synthesis of the anti, anti-dipropionate stereotriad have been reviewed. 3 We report herein a new approach to this problem involving the crotylation reaction of R-methyl β-hydroxy aldehydes with (Z)-crotyltrifluorosilane (5), 11 which provides the anti, anti-dipropionate 7 with excellent selectivity using 2, 3-anti β-hydroxy R-methyl aldehydes 4 as the starting material. We report as well an application of this methodology