Organic Chemistry Portal
Organic Chemistry Highlights

Monday, October 29, 2012
Tristan H. Lambert
Columbia University

Functional Group Protection

An efficient method for allylation of a sterically hindered alcohol in the presence of base sensitive functionality (cf. 1 to 2) has been developed (Tetrahedron Lett. 2012, 53, 1319. DOI: 10.1016/j.tetlet.2011.12.120) by Richard B. Silverman at Northwestern University. Mark S. Taylor at the University of Toronto found (J. Am. Chem. Soc. 2012, 134, 8260. DOI: 10.1021/ja302549c) that borinic acid 4 catalyzed the monofunctionalization of diols and carbohydrates such as 3.

The selective functionalization of unprotected peptides can be challenging, but Man-Kin Wong at Hong Kong Polytechnic University and Chi-Ming Che at the University of Hong Kong have shown (J. Am. Chem. Soc. 2012, 134, 2589. DOI: 10.1021/ja208009r) that selective N-terminal functionalization can be achieved with the alkynyl ketene 7, which allows for subsequent derivitization of the acylated products (e.g. 8) via click reactions with azides. To formylate amines such as morpholine (9), an N-heterocyclic carbene (e.g. 10) catalyzed procedure that utilizes CO2 and polymethylhydrosiloxane (PMHS) has been developed (J. Am. Chem. Soc. 2012, 134, 2934. DOI: 10.1021/ja211527q) by Thibault Cantat at the CEA in France.

For the protection of acyclic amino acid derivatives, Eiji Tayama at Niigata University has reported (Tetrahedron Lett. 2012, 53, 1373. DOI: 10.1016/j.tetlet.2012.01.013) a new protecting group, 1,2-dimethoxy-4,5-dimethylene, that is installed by double alkylation and can be removed with, for example, ethyl chloroformate to produce the corresponding carbamate (e.g 12 to 13). As far as protecting groups go, ethers can be especially challenging to remove, however a new procedure for the oxidative cleavage of glycol ethers, including dioxane, has been developed (Org. Lett. 2012, 14, 3218. DOI: 10.1021/ol301220s) by Zhong-Quan Liu at Lanzhou University. This copper catalyzed procedure employs carboxylic acids such as 14 and produces alkoxymethoxy esters 15. The cleavage of unactivated ethers such as dibutyl ether as a means to alkylate sulfonamides (cf. 16) has been reported (Synlett 2012, 595. DOI: 10.1055/s-0031-1290332) by Wei Zeng at South China University of Technology.

Protecting groups that are thermally labile offer the ability to achieve deprotection without added reagents. A new thermolabile protecting group has been developed (Tetrahedron Lett. 2012, 53, 666. DOI: 10.1016/j.tetlet.2011.11.122) by Marcin K. Chmielewski at the Polish Academy of Sciences based on 2-pyridyl-N-(2,4-difluorobenzyl)aminoethyl carbonates. Upon heating, molecules such as 17 undergo fragmentation by intramolecular displacement to produce bicyclic pyridinium 18 and alcohol 19.

Indium(III) fluoride has been shown (Tetrahedron Lett. 2012, 53, 697. DOI: 10.1016/j.tetlet.2011.11.135) by Sridhar Madabhushi at the Indian Institute of Chemical Technology to be an efficient catalyst for the hydrolysis of thioacetals, such as in the conversion of 20 to 21. For the protection of an electron-deficient olefin, use of the Diels-Alder adduct with cyclopentadiene is a strategy that has enjoyed much use. Do Hyun Ryu at Sungkyunkwan University has utilized (J. Org. Chem. 2012, 77, 2513. DOI: 10.1021/jo202357s) this approach for the scalable preparation of the complex vinyl bromide 23.

A chemoselective reduction of ketones in the presence of aldehydes (e.g. 24 to 25) was reported (Org. Lett. 2012, 14, 1306. DOI: 10.1021/ol300188e) by István E. Markó at the Université Catholique de Louvain by in situ protection of the aldehyde function as an O,S-aluminum acetal. This method recalls (Tetrahedron Lett. 1981, 22, 4213. DOI: 10.1016/S0040-4039(01)82107-9) the classic strategy using LDA by Daniel Comins, now at North Carolina State University. The reductive esterification of tosyl hydrazones such as 26 was reported (Eur. J. Org. Chem. 2012, 3925. DOI: 10.1002/ejoc.201200647) by Erick Cuevas-Yańez at UAEM-UNAM in Mexico and Carlos Valdés for the Universidad de Oviedo in Spain.

The team of Yasuhiro Ohki and Kazuyuki Tatsumi at Nagoya University and Martin Oestreich at the Technische Universität Berlin have developed (Org. Lett. 2012, 14, 2842. DOI: 10.1021/ol301089r) a base free, catalytic approach for the conversion of ketones such as 28 to their corresponding silyl enol ethers 30. Finally, an electrochemical deoxygenation of epoxides was reported (Org. Lett. 2012, 14, 22. DOI: 10.1021/ol2026944) by Jing-Mei Huang from South China University of Technology.

T. H. Lambert, Org. Chem. Highlights 2012, October 22.