Radicals phosphatoxy alkyl

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]. 

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. ... 

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... 

Table 4 Cumulative charges q and cumulative spin densities SD of the phosphatoxy groups in ground and transition states of phosphatoxy alkyl radicals 13a- 13e as calculated at the UB3LYP/6-3 lG(d)//UB3LYP/6-3 lG(d) level of theory38 14...

Extensive computational studies have been carried out on the )8-(acyloxy)alkyl and ff-( phosphatoxy)alkyl rearrangements by Radom and coworkers and by Zipse. These calculations in general support the possibility of concerted rearrangements taking place via 5-center-5-electron and 3-center-3-electron cyclic transition states [25, 26]. However, before such computations can be used as an aid in distinguishing between reaction pathways, it will be necessary for theoretical chemists to circumvent the present difficulties in calculating the radical ionic fragmentations. 

Two regioisomeric y9-(phosphatoxy)alkyl radicals (23) and (24), generated from Barton esters in the presence of ter/-butyl thiol and allyl alcohol, gave a single pair of diastereomeric tetrahydrofurans (26) in excellent yield. This result is most readily interpreted in terms of the highly regioselective quenching of a common radical cation (25) with formation of the more stable benzylic radical (Scheme 25) [49]. 

Scheme 25. Two regioisomeric / - phosphatoxy)alkyl radicals give one set of stereoisomeric tetra-hydrofurans via common radical cation...

Scheme 26. Diastereoselectivity in the cine substitution of /i-(phosphatoxy)alkyl radicals...

Beckwith, A. L. J., Crich, D., Duggan, P. J., and Yao, Q. W., Chemistry of beta-(acyloxy)alkyl and beta-(phosphatoxy)alkyl radicals and related species radical and radical ionic migrations and fragmentations of carbon-oxygen bonds, Chem. Rev., 97, 3273, 1997. 

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