Center for Molecular Discovery, Department of Chemistry, Boston University , 590 Commonwealth Avenue, Boston, Massachusetts 02215, United States.
Department of Chemistry, Northwestern University , 2145 Sheridan Road, Evanston, Illinois 60208, United States.
J Am Chem Soc. 2017 Feb 8;139(5):1998-2005. doi: 10.1021/jacs.6b11937. Epub 2017 Jan 25.
Allenes are useful functional groups in synthesis as a result of their inherent chemical properties and established reactivity patterns. One property of chemical bonding renders 1,3-substituted allenes chiral, making them attractive targets for asymmetric synthesis. While there are many enantioselective methods to synthesize chiral allenes from chiral starting materials, fewer methods exist to directly synthesize enantioenriched chiral allenes from achiral precursors. We report here an asymmetric boronate addition to sulfonyl hydrazones catalyzed by chiral biphenols to access enantioenriched allenes in a traceless Petasis reaction. The resulting Mannich product from nucleophilic addition eliminates sulfinic acid, yielding a propargylic diazene that performs an alkyne walk to afford the allene. Two enantioselective approaches have been developed; alkynyl boronates add to glycolaldehyde imine to afford allylic hydroxyl allenes, and allyl boronates add to alkynyl imines to form 1,3-alkenyl allenes. In both cases, the products are obtained in high yields and enantioselectivities.
烯丙基是合成中有用的功能基团，这是由于其固有化学性质和既定的反应性模式。化学成键的一个特性使得 1,3-取代的烯丙基具有手性，这使得它们成为不对称合成的有吸引力的目标。虽然有许多从手性起始原料合成手性烯丙基的对映选择性方法，但从非手性前体制备对映体富集的手性烯丙基的方法较少。我们在这里报道了一种通过手性联苯酚催化的不对称硼酸酯与亚磺酰腙的加成反应，以无痕迹的 Petasis 反应获得对映体富集的烯丙基。亲核加成的产物消除亚磺酸，生成丙二烯二氮，该丙二烯二氮进行炔烃行走，得到烯丙基。已经开发了两种对映选择性方法;炔基硼酸酯与乙二醇亚胺加成得到烯丙基羟基烯丙基，而烯丙基硼酸酯与炔基亚胺加成形成 1,3-烯基烯丙基。在这两种情况下，产物都以高产率和对映选择性获得。
