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Monday, March 23, 2009
Douglass F. Taber
University of Delaware

New Methods for Functional Group Conversion

Yujiro Hayashi of Tokyo University of Science and Teruaki Mukaiyama of the Kitasato Institute developed (Chem. Lett. 2008, 37, 592 ) a reduction-oxidation method for converting primary, secondary (such as 1, with clean inversion) and tertiary alcohols to sulfides. Peter A. Crooks of the University of Kentucky found (Chem. Lett. 2008, 37, 528 ) that tetrabenzylpyrophosphate 5 was an effective agent for condensing an acid 4 with an amine 6 to give the amide 7. This protocol, that runs in near quantitative yield in an hour at room temperature, with all impurities readily removable by washing with aqueous base and aqueous acid, appears to be well-suited both for scale-up, and for solid-phase synthesis.

Balchandra M. Bhanage of the University of Mumbai reported (Tetrahedron Lett. 2008, 49, 965 ) the reductive amination of aldehydes, including 8, and ketones to the corresponding amines, using H2 and an inexpensive Fe catalyst. André Charette of the Université de Montréal showed (J. Am. Chem. Soc. 2008, 130, 18 ) that the Hantzsch ester 12, in the presence of Tf2O, reduced amides selectively to amines. Esters, epoxides, ketones, nitriles and alkynes were stable to these conditions.

Matthew Tudge of Merck Rahway demonstrated (Tetrahedron Lett. 2008, 49, 1041 ) that Br2 in DME activated NaBH4, allowing facile reduction of esters, including the congested diester 14, at ambient temperature. David J. Procter of the University of Manchester made (J. Am. Chem. Soc. 2008, 130, 1136 ) the remarkable observation that six-membered ring lactones such as 16 were reduced to the corresponding diol with SmI2. Five-membered ring and seven-membered ring lactones were not reduced under these conditions.

Bruce H. Lipshutz of the University of California, Santa Barbara devised (Org. Lett. 2008, 10, 289 ) a convenient and economical procedure for CuH, using Cu and an inexpensive ligand in catalytic amounts, with PMHS as the bulk reductant. The reduction of 18 presumably proceeds by electron transfer, as with dissolving metal reduction, delivering 19 with the more stable trans ring fusion. In the presence of t-BuOH as a proton source, the reduction goes on to the alcohol 20. This may be the current method of choice for selectively reducing a cyclohexanone to the equatorial alcohol.

It is well known that tertiary allylic alcohols such as 21 can be oxidized to the corresponding enone 23 with chromium reagents. Yoshiharu Iwabuchi of Tohoku University observed (J. Org. Chem. 2008, 73, 4750 ) that the oxammonium salt 22 derived from TEMPO effected the same transformation. David E. Richardson of the University of Florida found (Tetrahedron Lett. 2008, 49, 1071 ) that H2O2 could be used to oxidize N-methylmorpholine in situ to the N-oxide, that in turn reoxidized catalytic OsO4. In the presence of the Sharpless ligand, the dihydroxylation proceeded with high ee. This approach could offer cost and waste stream advantages over currently used oxidants.

G. Sekar of the Indian Institute of Technology Madras, in Chennai, established (Tetrahedron Lett. 2008, 49, 2457 ) a convenient procedure for oxidizing primary alcohols such as 26 to the acid 27. Secondary alcohols were oxidized to ketones. Allylic and benzylic alcohols could be oxidized in preference to saturated alcohols. Tobin J. Marks of Northwestern University devised (Org. Lett. 2008, 10, 317 ) a La catalyst for the oxidative amination of aldehydes. In its present incarnation, excess aldehyde served as the reductant. If a less expensive reductant could be found, this would be a very useful procedure, avoiding the carboxylic acid activation usually required for amide formation.

D. F. Taber, Org. Chem. Highlights 2009, March 23.