Highly enantioselective Rh-catalyzed intramolecular Alder-ene reactions for the syntheses of chiral tetrahydrofurans.

Abstract

Alder±ene reactions are a powerful way to construct carbon±carbon bonds. The intramolecular version of these reactions can provide efficient routes to produce a variety of heterocyclic and carbocyclic compounds.[1] Since the thermal Alder±ene reaction requires high temperature, it has found limited applications in organic syntheses. In contrast, transition-metal-catalyzed Alder±ene reactions can be performed under mild conditions and therefore are widely applied to organic syntheses.[2] However, the enantioselective processes of metal-catalyzed Alder±ene reactions are relatively unexplored and the development of highly efficient catalysts still remains a great challenge.[3] Recently, we have developed Rhcatalyzed intramolecular Alder±ene reactions of enynes using a [{Rh(diphos)Cl}2] precursor.[4] Enantioselectivities between 65±98% ee were obtained by using 1,2-bis(phospholano)benzene (Duphos), (2R,2’R)-bis(diphenylphosphanyl)-(1R,1’R)dicyclopentane (BICP), or the related (2R,2’R)-bis(diphenylphosphinite)-(1R,1’R)-dicyclopentane (BICPO) as chiral ligands.[4a] Herein, we report a significant improvement of the catalytic system for these reactions. The new catalysts are prepared in situ by simply mixing a commercially available metal precursor and a ligand. Over 99% ee has been achieved for a number of substrates. To achieve high enantioselectivities for Rh-catalyzed Alder±ene reactions, we have screened a number of chiral phosphane ligands. The enyne 1a was chosen as a standard substrate to optimize the reaction conditions and the results are given in Table 1. In the absence of phosphane ligand, [{Rh(cod)Cl}2] was an ineffective catalytic precursor at either room temperature or 65 8C (Table 1, entries 1 and 2). However, [{Rh(nbd)Cl}2] (nbd1⁄4 norbornadiene) can be used as a catalyst precursor at 65 8C (Table 1, entry 6). Using the CnTunaphos ligands developed by our group,[5] high efficiency was observed. When rac-C4-Tunaphos was used as the ligand in the presence of [{Rh(cod)Cl}2] and AgSbF6, high conversion (100%) and a high yield (98%) were obtained at room temperature within 20 min (Table 1, entry 9). Control experiments indicated that there were big differences between this new catalytic system and the earlier protocol developed by us using [{Rh(diphosphane)Cl}2] as catalytic precursor. We previously reported that [{Rh(BINAP)Cl}2] (BINAP1⁄4 2,2’COMMUNICATIONS