Written by: Josephine S. Nakhla, Ph.D

Sames and coworkers have reported a Lewis-acid catalyzed [1,5] H-shift followed by C-C bond formation via reactive alkenyl oxocarbenium intermediates. Sames and coworkers have previously reported that expensive transition metal Lewis acids promoted cylizations of alpha,beta-unsaturated aldehydes and ketones, but were hampered with low yields and slow reaction times. The preparation of the corresponding acetals and ketals led to an improvement in the yield, reactivity and diastereoselectivity.  Thus, using the standard conditions of BF₃·Et₂O in CH₂Cl₂ at room temperature, a variety of tetrahydropyrans can be prepared, including those from more hindered and complex precursors. Finally, it was demonstrated that the acetals and ketals could be formed catalytically in situ when OHCH₂CH₂OH is added to the reaction mixture and that this method effects an increase in the rate (and in some cases, an increase in yield and diastereoselectivity) of the reaction, while also obviating the need for preparation of these precursors, and resulting in a binary catalytic system composed of BF₃·Et₂O as the catalyst and OHCH₂CH₂OH as the organocatalyst.

McQuaid, K. M.; Sames, D. J. Am. Chem. Soc. ASAP.

Written by: Dr. Sharbil J. Firsan

A mild, regioselective protocol for the C–H functionalization of heteroarenes has been reported by Lu and Falck.  This method, which is a marked improvement over existing ones for the direct silylation of heteroarenes, employs [{Ir(OMe)(cod)}₂] as catalyst, Et₃SiH as the inexpensive silylating reagent, and 4,4-di-tert-butyl-2,2-bipyridine as ligand.  Some of the attractive features of this process are:

• Moderate-to-high yields and high regioselectivities are observed.
• Only a small excess (3 equiv) of the silylating reagent is needed.
• Protection of the NH group in indoles is not required.
• Electron-donating and electron-withdrawing substituents in the heteroarene are tolerated.
• 2-Norbornene is used as a promoter and is believed to function as a hydrogen sink for the hydrogen produced in the reaction.

(1) Lu, B.; Falck, J. R. Angew. Chem., Int. Ed. 2008, 47, 7508.

Written by: Josephine S. Nakhla, Ph.D

Lectka and coworkers have recently disclosed a catalytic, asymmetric alpha-fluorination of acid chlorides using NFSi (N-Fluorobenzenesulfonimide) as the source of electrophilic fluorine upon formation of the ketene enolate in the presence of benzoylquinidine (BQd-10 mol %), Hunig’s base, and (1,3-dppp)NiCl₂ or trans-(PPh₃)₂PdCl₂ (3 mol %). Upon quenching (a variety of nucleophiles can be employed, such as water, alcohols, amines, and thiols), the product is released in excellent yield and enantiopurity. Initial attempted development of the reaction was impeded by low yields; the addition of a metal co-catalyst resulted in higher yields. The mechanism proposed is based on previous work by Lectka and coworkers and relies on the formation of a key metal-bound zwitterionic ketene enolate species, which is followed by reaction with NFSi, and transacylation to form the observed products.

Paull, D.H.; Scerba, M.T.; Alden-Danforth, E.; Widger, L. R. Lectka, T. J. Am. Chem. Soc. ASAP.