Of benzyl carbamates, to form amines

Electrolytic cleavage, 3 (review) of benzamides, to form amines, 356 of benzoate esters, to form alcohols, 102 of benzyl carbamates, to form amines, 336 of benzyl carbonates, to form alcohols, 109 of benzyl esters, to form carboxyl groups, 251... 

Amino Acids. Chloroformates play a most important role for the protection of the amino group of amino acids (qv) during peptide synthesis (32). The protective carbamate formed by the reaction of benzyl chloroformate and amino acid (33) can be cleaved by hydrogenolysis to free the amine after the carboxyl group has reacted further. The selectivity of the amino groups toward chloroformates results in amino-protected amino acids with the other reactive groups unprotected (34,35). Methods for the preparation of protected amino acids on an industrial scale have been developed (36,37). A wide variety of chloroformates have been used that give various carbamates that are stable or cleaved under different conditions. 

It has been mentioned earlier that when Burgess reagent is treated with primary alcohols the carbamate is formed rather than the dehydration product. The development of a benzyl Burgess reagent (49) was shown to convert primary alcohols to the corresponding amines that are conveniently protected with the Cbz group.15... 

Carbamates possess a more electron-rich nitrogen than amides or sulfonamides, and the intermolecular reaction of t-butylcarbamate with aryl halides to form t-Boc-protected anilines has been realized (Eq. 30). As one might expect from the increased rates for amine and indole arylation using the Pd(dba)2/P(t-Bu)3 catalyst, it is this system that allows for the arylation of i-butylcarbamate. Reaction of other carbamates, such as methyl or benzyl carbamate and oxazolinone, occurred in lower yield. However, reaction of t-butyl carbamate with bromoarenes occurred at 100 °C in yields ranging from 62% to 86% with electron-rich, electron-neutral, and sterically hindered or unhindered bromoarenes. Reactions of chloroarenes were again slower, but did occur at 130 °C to give Boc-protected aniline in 59% yield for reaction of chlorotoluene. 

Aresta and Quaranta studied the reactivity of alkylammonium N-alkylcarbamates (RNH3)02CNHR towards a different acylating substrate, such as dimethyl carbonate (DMC) [62a, b]. Carbamate salts (RNH3)02CNHR (R = benzyl, allyl, cyclohexyl), prepared in situ from aliphatic primary amines and C02, reacted with DMC to afford N-alkyl methylcarbamates (Equation 6.6). The reaction requires mild conditions (343-363 K 0.1 MPa C02 pressure) and can be carried out in DMC used as solvent and reagent. At 363 K, carbamate esters were obtained in satisfactory yield (45-92%) with high selectivity, as side products such as ureas, N,N-dialkylcarbamate esters, and alkylated amines were formed in very small amounts. 

In order to probe the effect of the substrate amine structure on this chemistry forming carbamates, a series of reactions were run under identical conditions to those described for Table I using benzyl chloride as the electrophile and tetramethylcyclohexyl guanidine as the co-base. The reaction rates are tabulated as relative rates with the rate for n-octyl amine set as 1. The results are summarized in Table II. 

The chemoselectivity of the reaction favors insertion in the most electron-rich C—H bond available to produce an oxazolidinone (Eqs. (5.6) and (5.7)) [33, 49, 50). When a bicyclic system is formed, the C—H amination reaction leans toward the formation of the cis-isomer. The scope of the reaction is large and many examples of carbamates derived from primary and tertiary alcohols are known. The use of carbamates derived from secondary alcohols is, however, more limited to substrates having conformational bias and/or very reactive C—H bonds (benzylic and allyl-ic) [51, 52]. Otherwise the formation of the corresponding ketone is observed, probably via a hydride shift process, similar to what is observed in C—H bond insertion with metal carbene [53, 54). 

A problem that is not entirely avoidable is the formation of imine byproducts via reaction of the released amine with the aldehydic group in the photoproduct. This occurrence could be suppressed with alkyl or aryl substitution at the benzylic position, leading to the formation of a less reactive ketone in comparison with the nitroso aldehyde formed with no substitution at the benzylic position. Imine byproduct formation is also less likely to occur in relatively nonpolar solvent systems, such as THF, which ultimately limits the application of the o-nitrobenzyl carbamate photoprotecting group to nonaqueous systems in this regard. 

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