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Monday, May 18, 2009
Douglass F. Taber
University of Delaware

Functional Group Protection

Alcohols are usually protected as alkyl or silyl ethers. Michael P. Jennings of the University of Alabama found (Tetrahedron Lett. 2008, 49, 5175 ) that pyridinium tribromide can selectively remove the TBS (or TES) protection from the primary alcohol of a protected primary-secondary alcohol such as 1. Propargyl ethers are useful because they are stable, but can be selectively removed in the presence of other protecting groups. Shino Manabe and Yukishige Ito at RIKEN showed (Tetrahedron Lett. 2008, 49, 5159 ) that SmI2 could reductively remove a propargyl group in the presence of acetonides (illustrated, 3), MOM, benzyl and TBS ethers. Hisanaka Ito of the Tokyo University of Pharmacy and Life Sciences took advantage (Org. Lett. 2008, 10, 3873 ) of the reducing power of Cp2Zr to selectively remove the allyl ethers from 5, to give 6. These conditions might also remove propargyl ethers.

Esters can also be useful protecting groups. Naoki Asao of Tohoku University developed (Tetrahedron Lett. 2008, 49, 7046 ) the o-alkynyl ester 7. Au catalyst in EtOH removed the ester, leaving benzoates, acetates, OTBS and OTHP intact. Alternatively, an o-iodobenzoate can be removed by Sonogashira coupling followed by the Au hydrolysis.

N-Formylation is usually accomplished using mixed anhydrides. Weige Zhang and Maosheng Chang of Shenyang Pharmaceutical University put forward (Chem. Commun. 2008, 5429) ) an intriguing alternative, heating a secondary amine 9 with KCN in the presence of dimethyl malonate to give 10.

Many of the current methods for amination that have been developed deliver the aryl amine. John F. Hartwig of the University of Illinois established (J. Am. Chem. Soc. 2008, 130, 12220 ) that exposure of the amine 11 to Boc2O followed by CAN led to the protected, dearylated amine 12.

Adam McCluskey of The University of Newcastle observed (Tetrahedron Lett. 2008, 49, 6962 ) that microwave heating removed Boc protecting groups when there was a free carboxylic acid elsewhere in the molecule. Michael Lefenfeld of SiGNa Chemistry and James E. Jackson of Michigan State University used (Org. Lett. 2008, 10, 5441 ) easily-handled Na/silica gel to remove primary and secondary sulfonamides (e.g. 1516). Methanesulfonamides were also removed under these conditions.

Carboxylates are good SN2 nucleophiles. Santos Fustero of the Universidad de Valencia took advantage of this (J. Org. Chem. 2008, 73, 5617 ) in developing a transesterification of TMSE esters. Exposure of 17 to TBAF in the presence of 18 gave 19. Akihiko Ouchi of the University of Tsukuba showed (J. Org. Chem. 2008, 73, 8861 ) that an aryl selenide such as 20 could be unmasked by photo-oxygenation to give the corresponding aldehyde 21. Secondary selenides gave ketones. Liam R. Cox of the University of Birmingham converted (Tetrahedron Lett. 2008, 49, 4596 ) halosilanes such as 22 to the corresponding alkyne 23 by exposure to TBAF.

There has been much discussion about the exact role microwaves play in promoting organic reactions. It is clear that microwaves can activate peptide bond rotation. This may be a factor in the observation (J. Am. Chem. Soc. 2008, 130, 10048 ) by Alexander Deiters of North Carolina State University that the rate of the hydrolysis of 24 to 25 by the β-glucosidase CelB from the hyperthermophilic archaeon Pyrococcus furiosus increased by at least four orders of magnitude under microwave irradiation.

D. F. Taber, Org. Chem. Highlights 2009, May 18.
URL: https://www.organic-chemistry.org/Highlights/2009/18May.shtm