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4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) is a potent lung carcinogen present in tobacco products, and exposure to it is likely one of the factors contributing to the development of lung cancer in cigarette smokers. To exert its carcinogenic effects, NNK must be metabolically activated into highly reactive species generating a wide spectrum of DNA damage. We have identified a new class of DNA adducts, DNA-RNA cross-links found for the first time in NNK-treated mice lung DNA using our improved high-resolution accurate mass segmented full scan data-dependent neutral loss MS

Expansion of the scope of the 1,3-diaza-Claisen rearrangement beyond bridged-bicyclic tertiary allylic amines has been investigated through a tethering strategy. Isothioureas tethered to tertiary allylic amines are converted to carbodiimides through a reaction with AgOTf/Et3N. Intramolecular cyclization of the tertiary allylic amine to the carbodiimide equilibrates with a zwitterionic intermediate. Heating the carbodiimide/zwitterion affords a rearrangement product. Heating carbodiimide/zwitterion with a deuterated allyl group results in the scrambling of the deuterium label, which is consistent with an ionic mechanism involving heterolytic cleavage of the allylic C-N bond, followed by trapping of the allyl cation at either terminal carbon. The ionic mechanism is attributed to silver salt contamination since pushing deuterium-labeled carbodiimide/zwitterion through silica gel prior to heating results in clean deuterium transposition consistent with a sigmatropic mechanism, and adding back silver salts results in deuterium scrambling. Overall, the tethering strategy broadens the scope of the rearrangement to simpler allylic substrates. Density functional theory (DFT) calculations of the sigmatropic rearrangement are in agreement with reactivity trends observed with reactions run under silver-free conditions.

Hofmann rearrangement of carboxamides to carbamates using Oxone as an oxidant can be efficiently catalyzed by iodobenzene. This reaction involves hypervalent iodine species generated in situ from catalytic amount of PhI and Oxone in the presence of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) in aqueous methanol solutions. Under these conditions, Hofmann rearrangement of various carboxamides affords corresponding carbamates in high yields.

The pseudocyclic iodine(V) oxidants, such as esters of iodoxybenzoic acid (IBX-esters) and 2-iodylphenol ethers, can serve as stable and efficient sources of oxygen in catalytic oxidations, and their reactivity is similar to the commonly used thermally unstable and potentially explosive iodosylbenzene. In a specific example, primary or secondary benzylic alcohols are selectively oxidized by isopropyl IBX-ester in the presence of μ-oxo-(tetra-tert-butylphthalocyaninato)iron(III) (0.1 mol equiv) in dichloromethane at room temperature in 0.5–2 h to afford the respective carbonyl compounds in 100% conversion and preparative yields 91–95% after column chromatography.

Hofmann rearrangement of carboxamides to carbamates using Oxone as an oxidant can be efficiently catalyzed by iodobenzene. This reaction involves hypervalent iodine species generated in situ from catalytic amount of PhI and Oxone in the presence of 1,1,1,3,3,3-hexafluoroisopropanol (HFIP) in aqueous methanol solutions. Under these conditions, Hofmann rearrangement of various carboxamides affords corresponding carbamates in high yields.

A new, mild, and efficient method to prepare various methyl carbamates as well as other alkyl carbamates is reported.

A new, mild procedure for the Hofmann rearrangement of aromatic and aliphatic carboxamides using (tosylimino)phenyl-λ(3)-iodane, PhINTs, as a reagent is reported. Because of the mild reaction conditions, this method is particularly useful for the Hofmann rearrangement of substituted benzamides, which usually afford complex reaction mixtures with other hypervalent iodine oxidants. The mild reaction conditions and high selectivity in the reaction of carboxamides with PhINTs allow the isolation of the initially formed labile isocyanates or their subsequent conversion to stable carbamates by treatment with alcohols.

The pseudocyclic iodine(V) oxidants, such as esters of iodoxybenzoic acid (IBX-esters) and 2-iodylphenol ethers, can serve as stable and efficient sources of oxygen in catalytic oxidations, and their reactivity is similar to the commonly used thermally unstable and potentially explosive iodosylbenzene. In a specific example, primary or secondary benzylic alcohols are selectively oxidized by isopropyl IBX-ester in the presence of μ-oxo-(tetra-tert-butylphthalocyaninato)iron(III) (0.1 mol equiv) in dichloromethane at room temperature in 0.5–2 h to afford the respective carbonyl compounds in 100% conversion and preparative yields 91–95% after column chromatography.