Organic Chemistry Portal
Organic Chemistry Highlights

Monday, November 11, 2013
Tristan H. Lambert
Columbia University

Functional Group Protection

Alfonso Iadonisi at the University of Naples Federico II developed (Eur. J. Org. Chem. 2013, 3137. DOI: 10.1002/ejoc.201300064) a procedure for the selective acetolysis of the perbenzylated sugar 1 to furnish 3 using isopropenyl acetate (2) instead of the more typical and high-boiling acetic anhydride. The (3,4-dimethoxylphenyl)benzyl (DMPBn) protecting group, which is removed (cf. 45) under acidic conditions in the presence of the cation scavenger 5, was developed (J. Org. Chem. 2013, 78, 5264. DOI: 10.1021/jo4004184) by David S. Larsen at the University of Otago as an alternative to the p-methoxybenzyl (PMB) group. Another new hydroxyl protecting group, the AzDMB group, which can be installed by simple acylation of (7+89) and removed under reductive conditions, was developed by Gijsbert A. van der Marel and Jeroen D. C. Codée of Leiden University. Stefan Grimme at the University of Bonn and Armido Studer at Westfälische-Wilhelms-Universität Münster found (Chem. Sci. 2013, 4, 2177. DOI: 10.1039/C3SC00099K) that NHC precatalyst 11 in the presence of NaH, benzaldehyde, and the oxidant 12 allows for the selective O-acylation of aminoalcohol 10 to 13.

The reductive deprotection of benzyl carbamate 14 using the strong organic reductant 15 under photolytic conditions was achieved (Angew. Chem. Int. Ed. 2013, 52, 2239. DOI: 10.1002/anie.201208066) by John A. Murphy at the University of Strathclyde. Liang-Qiu Lu and Wen-Jing Xiao at Central China Normal University found (Chem. Asian J. 2013, 8, 1090. DOI: 10.1002/asia.201300224) that mixed imide 17 could be detosylated under visible light photoredox catalysis in the presence of Hantzsch ester 18.

Frank Glorius at Westfälische-Wilhelms-Universität Münster developed (Org. Lett. 2013, 15, 1776. DOI: 10.1021/ol400639m) a ruthenium-catalyzed procedure for the N-formylation of amine 20 using methanol as the source of the formyl group. Protection of the thymine derivative 22 with a 2-(methoxycarbonyl)ethenyl (MocVinyl) group to produce 23 was developed (J. Org. Chem. 2013, 78, 5832. DOI: 10.1021/jo4006409) by Jaume Vilarrasa at the University of Barcelona. Deprotection of the MocVinyl group is readily achieved by treatment with a nucleophilic reagent such as pyrrolidine.

Robert H. Grubbs at Caltech demonstrated (Chem. Sci. 2013, 4, 1640. DOI: 10.1039/C3SC22256J) that ether 24 could be demethylated with triethylsilane and potassium tert-butoxide at high temperatures. The protection of catechol 26 as the dioxepane 27 and subsequent removal with aluminum(III) chloride was reported (Synlett 2013, 24, 741. DOI: 10.1055/s-0032-1318332) y Ya-Fei Ji at East China University of Science & Technology.

David A. Colby at Purdue University demonstrated (Org. Lett. 2013, 15, 3082. DOI: 10.1021/ol401265a) that the ketone function of substrate 28 could be selectively protected by treatment with N,O-dimethylhydroxylamine in the presence of trimethylaluminum and butyllithium. In situ treatment with methyl Grignard followed by hydrolysis then produced the tertiary alcohol 29. Selective deprotection of the 1,3-oxathiolane group of 30 was achieved (Tetrahedron Lett. 2013, 54, 2217. DOI: 10.1016/j.tetlet.2013.02.053) by Bo Liu at Sichuan University and the Shanghai Institute of Organic Chemistry.

Last but not least, Adrián Sánchez and Alfredo Vazquez demonstrated (Synthesis 2013, 45, 1364. DOI: 10.1055/s-0032-1316848) that α-amino acids including lysine (32) could be protected by treatment with 9-BBN. The free amino group of the corresponding oxazaborolidinone 33 was easily protected as a benzyl carbamate and then deprotected rapidly by treatment with 2-aminoethanol under microwave irradiation to furnish mono-protected 34.

T. H. Lambert, Org. Chem. Highlights 2013, November 11.