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Monday, July 11, 2005
Douglass Taber
University of Delaware

Best Synthetic Methods: Functional Group Transformations

An advantage of polymer-based reagents is that both the excess and the spent reagent are easily separated from the product. Bruno Linclau of the University of Southampton has reported (J. Org. Chem. 2004, 69, 5897. DOI: 10.1021/jo049239e) the preparation of a polymer-bound carbodiimide. Exposure of the polymer to alcohol gives a family of O-alkylisoureas that smoothly convert carboxylic acids to the corresponding esters. Methyl, benzyl, allyl and p-nitrobenzyl transfer smoothly. The polymeric t-butyl reagent could not be prepared.

Many procedures have been developed for the conversion of an alcohol to the iodide. Nevertheless, the ZrCl4-based procedure reported (Tetrahedron Lett. 2004, 45, 7451. DOI: 10.1016/j.tetlet.2004.08.056) by Habib Firouzabadi and Nasser Iranpoor of Shiraz University, Iran is promising. It works well with primary, secondary and tertiary alcohols under mild conditions, and there are no organic sideproducts.

The conversion of an alcohol to the amine is often a multi-step procedure. Jonathan M.J. Williams of the University of Bath has described (Chem. Commun. 2004, 1072. DOI: 10.1039/b402020k) a direct Ir-catalyzed procedure for this transformation. The reaction probably involves oxidation of the alcohol to the aldehyde, imine formation, and then reduction of the imine to the amine. No secondary examples were reported.

Oxidative decarboxylation of acids to alkenes is often accompanied by alkene rearrangement. Lukas J. Goossen of the Max-Planck-Institut, Mühlheim, has found (Chem. Commun. 2004, 724. DOI: 10.1039/b316613a) that in situ activation of the acid with phthalic anhydride and inclusion of the bis phosphine DPE-Phos substantially slow alkene isomerization, which can be essentially eliminated by running the reaction to only 80% conversion. Both linear and branched carboxylic acids work well.

The specific construction of trisubstituted alkenes is a continuing challenge. Shigeru Nishiyama of Keio University has described (Tetrahedron Lett. 2004, 45, 8273. DOI: 10.1016/j.tetlet.2004.09.085) the specific bromination-dehydrobromination of the allylic ester 9, delivering 10 as a 60:1 mixture of geometric isomers. Pd-mediated coupling led to the ester 11.

The least expensive starting organic “functional group” is a C-H bond. Two facile procedures for C-H activation have recently appeared. Melanie Sanford of the University of Michigan has developed (J. Am. Chem. Soc. 2004, 126, 9542. DOI: 10.1021/ja046831c) a procedure for specifically oxygenating methyl groups α to a ketone, by Pd-mediated oxidation of the derived methoxime 12. The process is catalytic in Pd. John F. Hartwig of Yale University has found (J. Am. Chem. Soc. 2004, 126, 15334. DOI: 10.1021/ja044933x) that methyl groups can also be specifically functionalized by Rh-mediated oxidative borylation. In the case of 14, steric effects direct the borylation to the ethyl group. The product borane 15 undergoes the expected oxidation and coupling reactions.

D. F. Taber, Org. Chem. Highlights 2005, July 11.