Reactions of methyl-substituted Hex-5-enyl and Pent-4-enyl radicals

Abstract

Relative and absolute kinetic data have been determined for ring closure of methyl-substituted hex-5-enyl radicals: 2-methyl- (10a), 3-methyl-(4a), 4-methyl-(5a), 2,2-dimethyl-(10c), 3,3-dimethyl-(4c) and 4,4-dimethyl-hex-5-enyl (5c) radicals, generated by interaction of tributylstannane with the corresponding bromides (1a)-(3a) and (1c)-(3c). Each radical undergoes regiospecific or highly regioselective 1,5-cyclization more rapidly than does the unsubstituted radical (4d). The rate enhancements, which arise mainly from lowering of the activation energy, can be rationalized in terms of the gem-dimethyl effect. 1,5-Ring closures of monosubstituted species are stereoselective: 2-methyl- and 4-methyl-hex-5-enyl radicals (10a) and (5a) give mainly trans products, whereas 3-methylhex-4- enyl radical gives mainly the cis. This behaviour reflects the effect of the substituent on the stabilities of cyclic transition complexes in chair-like conformations. Ring closure of 2,2-dimethylpent-4-enyl radical or of 3,3-dimethylpent-4-enyl radical (19) could not be detected.

Light on Unsaturated Hydrocarbons – “Gotta Heterofunctionalize Them All”

“…This can be explained by a Beckwith-type model (Scheme 35). [50] From mechanistic considerations, the reactivity is quite similar to that for the hydroetherification reported above (Scheme 29). Indeed, the alkene is first oxidized by the photoexcited catalyst.…”

Stereocontrolled Formation of Three Contiguous Stereogenic Centers by Free Radical Cyclization – Synthesis of (+)‐Iridomyrmecin and (–)‐Iso‐iridomyrmecin – Formal Synthesis of δ‐Skythantine

“…It leads preferentially to 1,5-cis-disubstituted cyclopentanes, according to the Beckwith transition state model. [3] This model postulates an early transition state, which resembles a "chair-like" cyclohexane ring with substituents in pseudo-equatorial rather than pseudo-axial [4] positions. In the second case Equation (2), we have a stereogenic center at C-2.…”

Athelstan L. J. Beckwith and the Flowering of Hex-5-enyl Radical Cyclization Chemistry. The Adelaide Years

“…The cyclization of the parent pent-4-enyl radical, also complicated by reversibility, has never been observed, and Athel had to resort to an estimate of the maximum possible rate at which it could have cyclized without products being detectable under the conditions used at the time. [3,[21][22][23] The essentially complete exo-selectivity of this unobserved cyclization would be expected to be similar to its immediate homologues on stereoelectronic grounds.…”

“…[29] Cyclizations of hex-5-enyl radical bearing simple alkyl or alkenyl substituents at the non-reacting C-2 15, C-3 16, and C-4 17 positions (Scheme 7) also proceed at enhanced rates compared with the parent unsubstituted radical 1. [22,[31][32][33] Ph.D. student Tony Lawrence conducted a systematic study of the effect of methyl substituents at all three positions and found modest rate enhancements (1.9-3.5) for single methyl groups and more substantial ones (10.8-16.3) for geminal dimethyl groups. Other singly substituted (vinyl, allyl, propyl) hexenyl radicals had roughly comparable relative cyclization rates to those with single methyl groups at the same position.…”

“…[26] Fairly quickly, examples of hexenyl systems with substituents at C-2 and C-3 undergoing stereoselective cyclizations were produced by other members of the Beckwith group. Hexenyl radicals with substituents at the 2-position 15 (R ¼ methyl, [22,33] vinyl [33] ) cyclized preferentially to the trans-1,3disubstituted cyclopentanes 19t, while those with 3-substituents 16 (R ¼ methyl, [22,33] vinyl, [33] allyl, [31] propyl [33] ) gave mainly cis-1,3-disubstituted cyclopentanes 19c (Scheme 7). The major: minor isomer ratios varied with position and substituent and ranged from 1.7 to 4.8.…”