All-catalytic, efficient, and asymmetric synthesis of alpha,omega-diheterofunctional reduced polypropionates via "one-pot" Zr-catalyzed asymmetric carboalumination-Pd-catalyzed cross-coupling tandem process.
All-catalytic, efficient, and asymmetric synthesis of alpha,omega-diheterofunctional reduced polypropionates via "one-pot" Zr-catalyzed asymmetric carboalumination-Pd-catalyzed cross-coupling tandem process.
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通过“一锅法”Zr催化不对称碳铝化-Pd催化交叉偶联串联工艺全催化、高效、不对称合成α,omega-二杂官能还原聚丙酸酯。
DOI：
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发表时间：
2005
影响因子：
15
通讯作者：
E. Negishi
中科院分区：
文献类型：
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作者：
T. Novák;Ze Tan;B. Liang;E. Negishi
发展了一种高效合成立体化学纯（>/= 99%ee和> 50/1dr）的α，ω-双杂官能还原聚丙酸酯的方法。该方法的基本特征是通过在（NMI）2ZrCl 2存在下由苯乙烯通过Zr催化的不对称碳铝化（ZACA）反应和在Zn（OTf）2和催化量的Pd（DPEphos）Cl 2存在下原位生成的异烷基丙氨烷的Pd催化的乙烯化，在两个步骤中以50%的产率将廉价的苯乙烯转化为2-甲基-4-苯基-1-戊醇（1）。该ZACA-Pd催化的乙烯化可以根据需要重复而无需纯化。在最终的ZACA反应之后，用O2氧化得到α-羟基-ω-苯基还原的聚丙酸酯，其可以通过色谱法完全或部分纯化。在乙酰化、Ru催化的Ph环的氧化裂解和用BH 3.THF还原之后，第二色谱纯化提供立体异构纯的α，ω-双杂官能还原聚丙酸酯（例如，9和11），其可以通过已知反应进一步转化为分别用于合成离子霉素（4）和疏螺旋体素（5）的关键中间体6和7。
A highly efficient method for the synthesis of stereochemically pure (>/=99% ee and >50/1 dr) alpha,omega-diheterofunctional reduced polypropionates has been developed. The essential features of the method are represented by the conversion of inexpensive styrene into 2-methyl-4-phenyl-1-pentanol (1) in 50% yield over two steps from styrene via Zr-catalyzed asymmetric carboalumination (ZACA) reaction in the presence of (NMI)2ZrCl2 and Pd-catalyzed vinylation of the in situ generated isoalkylalanes in the presence of Zn(OTf)2 and a catalytic amount of Pd(DPEphos)Cl2. This ZACA-Pd-catalyzed vinylation may be repeated as needed without purification. After the final ZACA reaction, oxidation with O2 provides alpha-hydroxy-omega-phenyl reduced polypropionates, which can be fully or partially purified by chromatography. After acetylation, Ru-catalyzed oxidative cleavage of the Ph ring, and reduction with BH3.THF, the second chromatographic purification provides stereoisomerically pure alpha,omega-diheterofunctional reduced polypropionates (e.g., 9 and 11) that can be further converted to key intermediates 6 and 7 for the synthesis of ionomycin (4) and borrelidin (5), respectively, by known reactions.