Barton esters amination

Free radicals generated under photochemical conditions from thiohydroxamates add readily to the NN double bond of diaziridines and in particular to the 3-bromo or 3-trifluoromethyl-3-phenyldiazirine to produce diaziridinyl radicals (Scheme 25) these intermediates undergo dimerization and fragmentation to yield the corresponding imines, which can be hydrolyzed to the corresponding amines. Barton esters can also be used for the direct preparation of nitroso compounds. From a synthetic standpoint, the yields are moderate and the method is limited to primary and secondary carboxylic acids, which form dimers as an end product. Tertiary nitroso compounds do not dimerize and further react with the radical present under the reaction conditions. 

O-acyl thiohydroxamates was initially thwarted by competing ionic reactions but eventually culminated in the introduction of 3-bromo or 3-(trifluoromethyl)-3-phenyl diazirine as extremely effective reagents [27]. In contrast to almost all of the other reactions of Barton esters described in this chapter, however, the reaction sequence does not involve a chain process. Thus, as outlined in Scheme 25, capture of the alkyl radical by the diazirine is followed by dimerization and subsequent loss of nitrogen to give the product imine from which the desired amide or amine is easily liberated by mild hydrolysis. Some typical yields are shown in the Scheme 26. 

The required nitrite esters 1 can easily be obtained by reaction of an appropriate alcohol with nitrosyl chloride (NOCl). The 3-nitroso alcohols 2 formed by the Barton reaction are useful intermediates for further synthetic transformations, and might for example be converted into carbonyl compounds or amines. The most important application for the Barton reaction is its use for the transformation of a non-activated C-H group into a functional group. This has for example been applied for the functionalisation of the non-activated methyl groups C-18 and C-19 in the synthesis of certain steroids. ... 

Barton and Narang" have prepared nitrate esters by treating primary and secondary alky-lamines with dinitrogen tetroxide in the presence of an amidine base like DBU. Wudl and Lee " conducted deamination reactions without any amidine base and reported much lower yields of nitrate ester product. The use of an amidine base is not necessary if the amine substrate... 

Chatgilialoglu studied (MesSijsGeH as a new radical hydrogen donor, and found that reduction of chlorides, bromides, and iodides, deoxygenation of secondary alcohols via a thiono ester (Barton-McCombie reaction), deamination of primary amines via isocyanides, removal of PhSe group, and replacement of a tertiary nitro group by hydrogen were extremely effective (Scheme 11.15) [31]. 

---