Synthesis of quaternary carbon stereogenic centers through enantioselective Cu-catalyzed allylic substitutions with vinylaluminum reagents.
Catalytic enantioselective allylic substitution (EAS) reactions, which involve the use of alkyl- or aryl-substituted vinylaluminum reagents and afford 1,4-dienes containing a quaternary carbon stereogenic center at their C-3 site, are disclosed. The C-C bond-forming transformations are promoted by 0.5-2.5 mol % of sulfonate bearing chiral bidentate N-heterocyclic carbene (NHC) complexes, furnishing the desired products efficiently (66-97% yield of isolated products) and in high site (>98% S(N)2')- and enantioselectivity [up to 99:1 enantiomer ratio (er)]. To the best of our knowledge, the present report puts forward the first cases of allylic substitution reactions that result in the generation of all-carbon quaternary stereogenic centers through the addition of a vinyl unit. The aryl- and vinyl-substituted vinylaluminum reagents, which cannot be prepared in high efficiency through direct reaction with diisobutylaluminum hydride, are accessed through a recently introduced Ni-catalyzed reaction of the corresponding terminal alkynes with the same inexpensive metal-hydride agent. Sequential Ni-catalyzed hydrometalations and Cu-catalyzed C-C bond-forming reactions allow for efficient and selective synthesis of a range of enantiomerically enriched EAS products, which cannot be accessed by previously disclosed strategies (due to inefficient vinylmetal synthesis or low reactivity and/or selectivity with Si-substituted derivatives). The utility of the protocols developed is demonstrated through a concise enantioselective synthesis of natural product bakuchiol.
Gao
Fang
F
Department of Chemistry, Merkert Chemistry Center, Boston College, Chestnut Hill, Massachusetts 02467, USA.
McGrath
Kevin P
KP
Lee
Yunmi
Y
Hoveyda
Amir H
AH
D000498:Allyl Compounds / Q000737:chemistry*; D000535:Aluminum / Q000737:chemistry*; D002244:Carbon / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D007202:Indicators and Reagents / Q000737:chemistry*; D013237:Stereoisomerism
D000498:Allyl Compounds; D007202:Indicators and Reagents; D002244:Carbon; D003300:Copper; D000535:Aluminum