| Description |
Transition metal-catalyzed synthesis of carbocycles and heterocycles is described. A Ni/NHC catalyst couples diynes to the C(a)-C(B) double bond of tropone, a type of reactions that is unprecedented for metal-catalyzed cycloadditions with aromatic tropone. Many different diynes were efficiently coupled to afford [5-6-7] fused tricyclic products, while [5-7-6] fused tricyclic compounds were obtained as minor byproducts in a few cases. The reaction has broad substrate scope and tolerates a wide range of functional groups, and excellent regioselectivity is found with unsymmetrical diynes. The mechanism of this interesting cycloaddition has been investigated using DFT calculations and it reveals an interesting 8p-insertion of tropone to afford [5-6-7] and [5-7-6] fused tricyclic products. A unique and catalytic way to synthesize challenging eight-membered heterocycles is disclosed. The Ni/P(p-tol)3 catalyst promoted the cycloaddition of a variety of 1,3-dienes with 3-azetidinones and 3-oxetanones to afford both monocyclic and bicyclic azocine and oxocine ring systems, respectively. Interestingly, the cycloaddition with 1,3-diene conjugated with a p-methoxylphenyl group led to a 3-piperidinone product instead of the azocine ring. The synthesis of the these interesting eight-membered heterocycles involved the challenging steps of C(sp2)-C(sp3) bond activation and C(sp3)-C(sp3) reductive elimination. An efficient and convenient procedure that generates the active Ni(0) catalyst in situ from cheap, air stable Ni(II) precursors is developed for the [4+2]-cycloaddition of alkynes and 3-azetidinones. The reaction affords useful 3-dehydropiperidinones in comparable yields to the reported Ni(0) procedure. Additionally, the cycloaddition with 3-oxetanone afforded the 3-dehydropyranone product. The application of this methodology to the total synthesis of (+)-septicine is also described. A protocol for the Suzuki-Miyaura coupling of heteroaryl boronic acids and vinyl chlorides that minimizes protodeboronation is disclosed. A combination of catalytic amounts of Pd(OAc)2 and SPhos in conjunction with CsF in isopropanol effectively affords a variety of coupled products. Surprisingly, a dramatic temperature dependence in product selectivity was observed. |
