Stereospecific carbinolamine formation

Intramolecular rhodium-catalyzed carbamate C-H insertion has broad utility for substrates fashioned from most 1° and 3° alcohols. As is typically observed, 3° and benzylic C-H bonds are favored over other C-H centers for amination of this type. Stereospecific oxidation of optically pure 3° units greatly facilitates the preparation of enantiomeric tetrasubstituted carbinolamines, and should find future applications in synthesis vide infra). Importantly, use of PhI(OAc)2 as a terminal oxidant for this process has enabled reactions with a class of starting materials (that is, 1° carbamates) for which iminoiodi-nane synthesis has not proven possible. Thus, by obviating the need for such reagents, substrate scope for this process and related aziridination reactions is significantly expanded vide infra). Looking forward, the versatility of this method for C-N bond formation will be advanced further with the advent of chiral catalysts for diastero- and enantio-controlled C-H insertion. In addition, new catalysts may increase the range of 2° alkanol-based carbamates that perform as viable substrates for this process. 

Smith, J., Harris, T.M., Lloyd, R.S., Rizzo, C.J., and Stone, M.P. (2006) Stereospecific formation of interstrand carbinolamine DNA cross-links by crotonaldehyde- and acetaldehyde-derived a-CH3-y-OH-l,N2-propano-2 -deoxyguanosine adducts in the 5 -CpG-3 sequence. Chem. Res. Toxicol, 19, 195-208. 

Formation of a carbinolamine as the short-lived Schiff base precursor (C) could be trapped by Hash freezing of 2-keto-3-deoxy-6-phosphogluconate aldolase in the presence of its natural donor substrate pyruvate [46]. Stereospecificity of the reaction seems to be ensured mostly by hydrophobic contact of the pyruvate methyl group in the active site. 

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