Division of Pharmaceutical Sciences and Department of Chemistry, University of Wisconsin, Madison, Wisconsin 53705, USA.
J Am Chem Soc. 2011 Sep 14;133(36):14443-51. doi: 10.1021/ja205700p. Epub 2011 Aug 18.
A systematic investigation of the regioselectivities and stereoselectivities of (4 + 3) cycloadditions between unsymmetrical furans and a chiral oxazolidinone-substituted oxyallyl is presented. Cycloadditions were performed using an oxyallyl containing a (R)-4-phenyl-2-oxazolidinone auxiliary (2(Ph)), under either thermal or ZnCl(2)-catalyzed conditions. Reactions of 2(Ph) with 2-substituted furans gave syn cycloadducts selectively, while cycloadditions with 3-substituted furans gave selectively anti cycloadducts. The stereoselectivities were in favor of a single diastereoisomer (I) in all but one case (2-CO(2)R). Density functional theory calculations were performed to explain the selectivities. The results support a mechanism in which all cycloadducts are formed from the E isomer of the oxyallyl (in which the oxazolidinone C═O and oxyallyl oxygen are anti to each other) or the corresponding (E)-ZnCl(2) complex. The major diastereomer is derived from addition of the furan to the more crowded face of the oxyallyl. Crowded transition states are favored because they possess a stabilizing CH-π interaction between the furan and the Ph group.
本文系统研究了不对称呋喃与手性恶唑烷酮取代的氧杂丙烯基之间的（4 + 3）环加成的区域选择性和立体选择性。环加成反应在含有（R）-4-苯基-2-恶唑烷酮辅助基（2（Ph））的氧杂丙烯基的条件下，在热或 ZnCl2 催化条件下进行。2（Ph）与 2-取代呋喃的反应选择性地生成顺式环加成产物，而与 3-取代呋喃的环加成则选择性地生成反式环加成产物。除了一种情况（2-CO（2）R）外，所有情况下的立体选择性都有利于单一非对映异构体（I）。进行了密度泛函理论计算以解释选择性。结果支持了一种机制，其中所有环加成产物均由 E 异构体的氧杂丙烯基（其中恶唑烷酮 C═O 和氧杂丙烯基氧彼此反式）或相应的（E）-ZnCl2 配合物形成。主要的非对映异构体是由呋喃加成到氧杂丙烯基较拥挤的面上生成的。拥挤的过渡态是有利的，因为它们在呋喃和 Ph 基团之间具有稳定的 CH-π相互作用。
