Phosphatoxy

A 1,2-shift has been observed in radicals bearing an OCOR group at the p-carbon where the oxygen group migrates as shown in the interconversion of 36 and 37. This has been proven by isotopic labeling experiments and other mechanistic explorations. A similar rearrangement was observed with phosphatoxy alkyl radicals such as 38. ... 

Phosphorylated derivatives of /3-nitroalcohols, upon exposure to Bu3SnH and AIBN, afford /3-(phosphatoxy)alkyl radicals. These radicals undergo heterolytic cleavage of the phosphate group to afford an alkene radical cation which is trapped intramolecularly in a tandem polar/radical crossover sequence. Derivative 37 (Scheme 13), through a 6-exol 5-exo overall cyclization, afforded the indolizidine derivative 38 as an equimolecular mixture of two diastereoisomers <2003JA7942, 2002OL2573>. 

In parallel with the development of the heterolysis of b-substituted alkyl radicals, a rearrangement reaction was observed and extensively studied in organic solvents. This rearrangement was first noted for b-(acyloxy)alkyl radicals (Scheme 5) by Surzur et al. [48] and, later, for b-(phosphatoxy)alkyl radicals by the Crich and Giese groups [49,50]. 

The rearrangements of b-(acyloxy), (i-(phosphatoxy)alkyl, and related systems have been reviewed [51,52] and representative kinetic data are given in Table 2 above. As revealed by isotopic labeling experiments, the acyloxy... 

Scheme 12 1,2-phosphatoxy shifts in a cyclic phosphate ester... 

By means of diastereomeric probes, it has been demonstrated that the vicinal nucleophilic displacement of a diethylphosphate group from a jS-(phosphatoxy)alkyl radical may occur through backside or frontside attack, depending on steric constraints. ... 

The chemistry of radical sites adjacent to phosphatoxy centers elicited interest because of the involvement of such species in DNA degradation processes. These species can give rise to rearrangement, elimination, and substitution products, and for some time concerted eliminations and migrations as well as heterolysis to a radical cation and a phosphate anion were considered to be involved (Scheme 2). Recently, experimental studies of the l,2-dibenzyl-2-(diphenylphosphatoxy)-2-phenylethyl radical and complementary theoretical studies of l,l-dimethyl-2-(dimethylphosphatoxy)ethyl radical have been interpreted as indicating that a radical cation/anion pathway with initial formation of 49 is favored. ... 

A much simpler situation is the anion loss from an a-alkoxyalkyl radical with a leaving group in the P-position, such as the phosphate release from the 2-phosphato-methoxyethyl radical (Behrens et al. 1978 for some further reactions of P-(phosphatoxy)alkyl radicals see Whitted et al. 1999 Crich et al. 2000). This reaction only proceeds by a heterolytic cleavage into a radical cation and a phosphate ion. The rate of this reaction strongly depends on the protonation state of the phosphate group [reactions (40)-(44)]. 

Crich D, Huang X, Newcomb M (2000) Inter- and intramolecular pathways for the formation of tet-rahyrofurans from (5-(phosphatoxy)alkyl radicals. Evidence for a dissociative mechanism. J Org Chem 65 523-529... 

A comprehensive review of experimental as well as theoretical studies has been compiled by Beckwith et al. in 1997 for those systems with acyloxy or phosphatoxy substituents.3 This account will therefore concentrate on the theoretical studies published since then together with the relevant experimental results. Particular... 

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