Allylic sulfones in solid-phase synthesis: Preparation of cyclobutylidenes
Allylic sulfones in solid-phase synthesis: Preparation of cyclobutylidenes
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DOI：
10.1021/jo990954b
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发表时间：
1999-11-12
影响因子：
3.6
通讯作者：
Kurth, MJ
中科院分区：
文献类型：
--
作者：
Cheng, WC;Halm, C;Kurth, MJ
聚合物结合的烯丙基砜（参见9)用于与表氯醇的偕环烷基化以产生顺式-苯磺酰基环丁醇衍生物（参见，11)一步到位在该固相合成序列的最后一步中，筛选铜酸盐、有机钼和有机钯试剂以获得用于从树脂“无痕迹”裂解亚环丁基产物的最佳方案。其中，钯催化的烯丙基烷基化反应是最有效的。此外，在烯丙基片段的较少受阻末端的高度区域选择性亲核攻击（即，总的S（N）2 ′亚磺酸酯置换）。通过引入不同的烯丙基取代基、0-官能化和C-亲核试剂来证明亚环丁基多样化，以制备八种亚环丁基衍生物的示范文库（即，4）的衍生物，总收率为30-38%。
Polymer-bound allyl sulfones (cf. 9) were utilized in geminal cycloalkylations with epichlorohydrin to generate a cis-phenylsulfonylcyclobutanol derivative (cf. 11) in one step. In the final step of this solid-phase synthetic sequence, cuprate, organomolybdenum, and organopalladium reagents were screened to obtain an optimal protocol for "traceless" cleavage of cyclobutylidene products from the resin. Among these, palladium-catalyzed allylic alkylation was the most efficient. In addition, highly regioselective nucleophilic attack at the less hindered terminus of the allyl fragment (i.e., overall S(N)2' sulfinate displacement) was observed. Cyclobutylidene diversification was demonstrated by incorporating different allylic substituents, O-functionalizations, and C-nucleophiles to prepare a demonstration library of eight cyclobutylidene derivatives (i.e., derivatives of 4) in four steps and 30-38% overall yield from lithium polystyrene/divinylbenzene sulfinate.