Written by: Josephine S. Nakhla, PhD.

Gaspar and Carreira have recently addressed a well-known limitation in the literature for the catalytic hydrochlorination of unactivated olefins using a cobalt-derived catalyst. Most hydrochlorinations are inherently limited since common methods are restricted to strained olefins or alkenes providing stabilized intermediates or require the use of HCl, which is not conducive in the synthesis of molecules containing acid-sensitive functionalities. The reaction developed by Gaspar and Carreira proceeds with complete regioselectivity providing the Markovnikov product under two similar sets of reaction conditions—using cobalt Catalyst 1, PhSiH₃, EtOH, and TsCl as the chloride source or using Co(BF₄)₂·6H₂O (6-12 mol %), Ligand 1 (SALDIPAC), t-BuOOH (30 mol%), PhSiH₃, TsCl, and EtOH. The authors propose a radical pathway to explain the formation of the hydrochlorination products, which presumably is initiated by formation of a cobalt-hydride complex (from the Co-catalyst and PhSiH₃). Hydrocobaltation followed by capturing by TsCl, either via an alkyl radical or via direct reaction with the organocobalt species provides a general means for the regioselective formation of organochlorides, including monosubstituted olefins.

 Gaspar, B. and Carreria, E. M. Angew. Chem. Int. Ed. 2008, 47, ASAP.

Written by: Dr. Sharbil J. Firsan

1-Ethynylcyclohexanol acts as an effective acetylene substitute in the efficient synthesis of monarylated (85–99% isolated yields) and diarylated acetylenes (24–95% isolated yields) by the Sonogashira coupling.  In that regard, it is comparable to 2-methyl-3-butyn-2-ol and trimethylsilylacetylene in some cases, but it surpasses them in several others.  Its main advantages are:

•  The unsymmetrical diarylacetylenes can be synthesized in a one-pot sequence of two Sonogashira couplings without isolating the intermediate monoarylated acetylenes, which can be only moderately stable.
• Following the second Sonogashira coupling reaction, the chemically inert cyclohexanone is released as a byproduct.
• It is commercially available and moderately priced.

Csékei, M.; Novák, Z.; Kotschy, A. Tetrahedron 2008, 64, 975.

Written By: Dr. Sharbil J. Firsan 

Dirhodium(II) tetracarboxylates, in particular Rh₂(esp)₂, effectively catalyze a novel reaction cascade leading to sterically congested, fused 5,7 and 6,7 bicyclic ring systems.  This metallonitrene–alkyne metathesis sequence leads to the formation of new C–N, C–O, and C–C bonds intramolecularly from simple starting materials.  This reaction series tolerates alkyl and aryl substituents at either end of the alkyne, and allyl and benzyl groups are cleanly transferred.  Since the initially formed imine products are sensitive to hydrolysis on purification, they are more conveniently isolated as the corresponding amines after in situ reduction with sodium borohydride.

Thornton, A. R.; Blakey, S. B. J. Am. Chem. Soc. 2008, 130, 5020.

Written by: Josephine S. Nakhla, PhD.

Indoles and their derivatives constitute an important class of compounds due to their frequent occurrence in natural products, bioactive compounds and pharmaceuticals, and organic materials. Various Pd-catalyzed methods have been developed for substituting on the indole ring including the N1, C2, C3 positions; however, methods for further C-3 functionalization on already substituted and hindered 2,3-disubstituted indoles to generate indolenines with concomitant formation of a quaternary center has been a known challenge. Rawal and coworkers have developed a nice method for allylation of sterically congested 2,3-disubstituted indoles. Substitution occurs selectively in the 3-position using allyl ester electrophiles and an optimal catalyst system consisting of a combination of Pd₂(dba)₃ and P(2-fur)₃ as the ligand. Allyl indolenines were prepared in good to excellent yields (63-99% isolated yields). Substituted olefins also proved successful in providing more complex indolenines. Finally, the method was investigated in an increasingly complex setting utilizing several indole-containing natural products. The method is remarkably robust and allows for the facile preparation of novel allylated derivatives of (+/-)-geissoschiol (single diastereomer), yohimbine (single diastereomer), and reserpine (1:1 dr).
 
 

Kagawa, N.; Malerich, J. P.; Rawal, V. H. Org. Lett. 2008, 10, 2381.