Athelstan L. J. Beckwith

Regio- and stereo-selectivity of alkenyl radical ring closure: a theoretical study

Abstract A theoretical study has been undertaken of the relative rates and the regio- and stereo-chemistry of ring closure of a variety of alkenyl, alkenylaryl, alkenylvinyl and similar radicals. The method involves the application of MM2 force-field calculations to model transition structures for which the dimensions of the arrays of reactive centres have been obtained by MNDO-UHF techniques. The results, which generally accord with guidelines based on stereochemical considerations, show excellent qualitative and satisfactory quantitative agreement with experimental data. The method has been successfully applied to complex systems including ring closure of alkylperoxy radicals, and formation of the triquinane system by three consecutive cyclisations.

Kinetics and mechanism of some vinyl radical cyclisations

Abstract The vinyl radicals 2a, 2b, and 11 each undergo fast exo ring closure to give 5a, 5b, and 12, the first two of which readily rearrange to ring-expanded radicals.

A force-field study of alkenyl radical ring closure

Abstract In accord with stereoelectronic considerations there is a good correlation between the relative rates, regiochemistry, and stereochemistry of ring closure of ω-alkenyl radicals, and the strain energies of transition structures determined by force field calculations.

A comparison of methods for measuring relative radical stabilities of carbon-centred radicals

This article discusses and compares various methods for defining and measuring radical stability, including the familiar radical stabilization energy (RSE), along with some lesser-known alternatives based on corrected carbon-carbon bond energies, and more direct measures of the extent of radical delocalisation. As part of this work, a large set of R-H, R-CH(3), R-Cl and R-R BDEs (R = CH(2)X, CH(CH(3))X, C(CH(3))(2)X and X = H, BH(2), CH(3), NH(2), OH, F, SiH(3), PH(2), SH, Cl, Br, N(CH(3))(2), NHCH(3), NHCHO, NHCOCH(3), NO(2), OCF(3), OCH(2)CH(3), OCH(3), OCHO, OCOCH(3), Si(CH(3))(3), P(CH(3))(2), SC(CH(3))(2)CN, SCH(2)COOCH(3), SCH(2)COOCH(3), SCH(2)Ph, SCH(3), SO(2)CH(3), S(O)CH(3), Ph, C(6)H(4)-pCN, C(6)H(4)-pNO(2), C(6)H(4)-pOCH(3), C(6)H(4)-pOH, CF(2)CF(3), CF(2)H, CF(3), CCl(2)H, CCl(3), CH(2)Cl, CH(2)F, CH(2)OH, CH(2)Ph, cyclo-CH(CH(2))(2), CH(2)CH[double bond, length as m-dash]CH(2), CH(2)CH(3), CH(CH(3))(2), C(CH(3))(3), C[triple bond, length as m-dash]CH, CH[double bond, length as m-dash]CH(2), CH[double bond, length as m-dash]CHCH(3), CHO, CN, COCH(3), CON(CH(2)CH(3))(2), CONH(2), CONHCH(3), COOC(CH(3))(3), COOCH(2)CH(3), COOCH(3), COOH, COPh), and associated radical stability values are calculated using the high-level ab initio molecular orbital theory method G3(MP2)-RAD. These are used to compare the alternative radical stability schemes and illustrate principal structure-reactivity trends.

The mechanisms of the rearrangements of allylic hydroperoxides: 5α-hydroperoxy-3β-hydroxycholest-6-ene and 7α-hydroperoxy-3β-hydroxycholest-5-ene

The rearrangement of 5α-hydroperoxy-3β-hydroxycholest-6-ene in solution under 18O2, gives isotopically normal 7α-hydroperoxy-3β-hydroxycholest-5-ene, whereas the epimerization of this product to give 7β-hydroperoxy-3β-hydroxycholest-5-ene involves incorporation of 73–83% of 18O2 into the hydroperoxy group. These two reactions proceed through the corresponding hydroperoxyl radicals, which have different e.s.r. spectra and which therefore must exist as separate and distinct species.The former reaction shows a first-order dependence on hydroperoxide concentration, and a half order dependence on t-butyl hyponitrite which was added as an initiator.It is suggested that the first reaction involves a sigmatropic [2,3]-rearrangement, whereas the second reaction proceeds through a dissociative mechanism.

Cyano or acyl group migration by consecutive homolytic addition and β-fission

Suitably constituted aryl and alkyl radicals readily rearrange by 1,2- or 1,4-acyl or cyano migration.

The frequently overlooked importance of solvent in free radical syntheses

This tutorial review is designed to dispel the myth, still believed by many synthetic organic chemists, that radical-based syntheses are free from significant solvent effects. However, many synthetically valuable radical reactions do exhibit large kinetic solvent effects. It is therefore important to select the solvent for any proposed radical synthesis with considerable care if good product yields are to be achieved.

Formation of fused bi- and tri-cyclic β-lactams by radical ring closure

Abstract Methods involving intramolecular homolytic addition or intramolecular S H 2 processes in suitably constituted radicals provide convenient routes to bi- and tri-cyclic systems containing the azetidinone moiety.

Diastereoselective formation of cyclic carbonates by cyclization of alkenyloxycarbonyloxy radicals

Abstract The alkenyloxycarbonyloxy radical ( 8 ) derived from trans -hex-2-en-1-ol via the N -hydroxypyridine-2-thione carbonate ( 4 ) undergoes fast ( k c > 4.0 × 10 8 s −1 at 80°C) cyclization exclusively in the exo mode to give a cyclic radical ( 9 ) which is converted into products ( 6,7 ) by diastereoselective S H 2 reactions; radicals derived from homoallylic alcohols behave similarly.

The synthesis of indolizidine and quinolizidine ring systems by free radical cyclization of 4-aza-6-methoxycarbonyl-5-hexenyl radicals

Abstract The formation of bicyclic amines by the intramolecular cyclization of 4-aza-6-methoxycarbonyl-5-hexenyl radicals is described. The direct attachment of a nitrogen atom to the double bond changes the electronic nature of the alkene such that the cyclization is less efficient than the all carbon analogue or the other aza-substituted 5-hexenyl cyclizations.The reaction has been used in a short, convenient synthesis of a variety of indolizidines from methyl nicotinate. In addition, the cyclization was used as the key step in a short synthesis of (±)-epilupinine from methyl nicotinate.