Organic Chemistry Portal
Organic Chemistry Highlights

Monday, March 15, 2010
Douglass F. Taber
University of Delaware

Organic Functional Group Protection

Masato Kitamura of Nagoya University investigated (Chem. Lett. 2009, 38, 188. DOI: 10.1246/cl.2009.188) the Ru-mediated deprotection of allyl ethers such as 1. The same catalyst was effective for the preparation of allyl ethers from the alcohol 2 and allyl alcohol. István E. Markó of the Université Catholique de Louvain showed (Org. Lett. 2009, 11, 2752. DOI: 10.1021/ol900828x) that SmI2 effected the reductive cleavage of an aryl ester 3, liberating the alcohol 4.

Osamu Onomura of Nagasaki University found (Tetrahedron Lett. 2009, 50, 1466. DOI: 10.1016/j.tetlet.2009.01.063) that catalytic CuCl2 mediated the selective monoallylation of symmetrical diols such as 5. Péter Fügedi of the Hungarian Academy of Sciences, Budapest observed (Tetrahedron Lett. 2009, 50, 2914. DOI: 10.1016/j.tetlet.2009.03.194) that TMSOTf catalyzed the selective reduction of 7 to the benzyl ether. BH3•NMe2 delivered the opposite regioisomer.

Direct amination of an ester has been a long-sought transformation. Vladimir B. Birman of Washington University found (Org. Lett. 2009, 11, 1499. DOI: 10.1021/ol900098q) that 1,2,4-triazole 11 in combination with DBU was an effective catalyst for this reaction. Unactivated esters required higher reaction temperatures.

Deprotection of amides often requires vigorous conditions, and the product free amines can be challenging to handle. Stefan G. Koenig of Sepracor Chemical Process devised (Org. Lett. 2009, 11, 433. DOI: 10.1021/ol802482d) a simple protocol for in situ formation and hydrolysis of the imidoyl chloride from 12 that delivered the amine hydrochloride 13 directly. Remarkably, benzamides are stable under these conditions. Hongmei Li of Merck Process devised (Tetrahedron Lett. 2009, 50, 1010. DOI: 10.1016/j.tetlet.2008.12.050) a related procedure, heating the more reactive trifluoroacetamide 14 with stoichiometric p-toluenesulfonic acid, and isolating the product as the p-toluenesulfonate salt 15.

There has been a reluctance to use sulfonamide protecting groups, as they have been thought to be difficult to remove. Göran Hilmersson of the University of Gothenburg established (Org. Lett. 2009, 11, 503. DOI: 10.1021/ol802243d) that SmI2 instantaneously deprotected 16.

Daniel E. Falvey of the University of Maryland designed (J. Org. Chem. 2009, 74, 3894. DOI: 10.1021/jo900182x) the benzyl ester 17, that was readily released under photolysis. Stanislaw Krompiec of the University of Silesia described (Tetrahedron Lett. 2009, 50, 1193. DOI: 10.1016/j.tetlet.2008.12.110) what appears to be a general strategy for the preparation of ortho esters such as 21.

To incorporate a sulfonic acid in a synthetic target, it is usually necessary to bring it along in protected form, then release the free sulfonic acid at the end of the synthesis. Scott D. Taylor of the University of Waterloo devised (J. Org. Chem. 2009, 74, 3583. DOI: 10.1021/jo900122c) the trichloroethyl ester 22 for this purpose. Masahiro Hirama of Tohoku University employed (Angew. Chem. Int. Ed. 2009, 48, 1110. DOI: 10.1002/anie.200805518) the ester mesylate 24 as a protected form of the alkene 25. Note that the sensitive 25 was stable to the SmI2 reduction.

D. F. Taber, Org. Chem. Highlights 2010, March 15.