Intramolecular Homolytic Substitution Chemistry:  An ab Initio Study of 1,n-Chalcogenyl Group Transfer and Cyclization Reactions in Some ω-Chalcogenylalkyl Radicals

Abstract

Ab initio calculations using a pseudopotential (DZP) basis set and with the inclusion of electron correlation (MP2) predict that intramolecular homolytic substitution at the chalcogen atom in the 4-chalcogenyl-1-butyl (4), 5-chalcogenyl-1-pentyl (5), 6-chalcogenyl-1-hexyl (6), and 7-chalcogenyl-1-heptyl radicals (7) proceeds preferentially with the degenerate translocation of the chalcogen-containing moiety for radicals 6 and 7 and with ring closure in the case of the lower homologues (4, 5). All reactions involving homolytic substitution at the tellurium atom are predicted to proceed with the involvement of [9-Te-3] hypervalent intermediates, while the analogous reactions involving sulfur and selenium are calculated to proceed without the involvement of intermediates at all levels of theory, except during the 1,6-translocation of selanyl in which a shallow local minimum was located on the potential-energy surface at the MP2/DZP level of theory. Energy barriers for ring-closure reactions of between 48.4 (cyclization of 4: E = Te) and 162.6 kJ·mol-1 (cyclization of 5: E = S) are calculated and are expected to decrease significantly with the inclusion of better leaving groups. Energy barriers for 1,n-translocation reactions of between 62.8 (1,7-tellanyl transfer) and 139.3 kJ·mol-1 (1,5-sulfanyl transfer) are predicted at the MP2/DZP level of theory; these high energy barriers are presumably a consequence of unfavorable factors associated with ring size and long carbon−chalcogen separations in transition states and intermediates (9−13) which lead to significant deviations from the ideal arrangement of attacking and leaving radicals preferred in homolytic substitution reactions at chalcogen. The dependence of transition-state energy on attack angle at chalcogen has been explored for the attack of methyl radical at methanethiol. Attack angles of around 110° are calculated to lead to increases in the energy barrier of about 140 kJ·mol-1 when compared with the preferred (159.5°) arrangement of attacking and leaving groups. The mechanistic implications of these predictions are discussed.

Intramolecular Homolytic Substitutions in Synthesis

“…Five-membered transition states are most favorable because the required collinear arrangement of attacking and leaving radicals is more easily accommodated with four bridging atoms than with the five involved in the formation of the analogous six-membered ring. 8 As can be seen from the data in Table 1, six-membered rings are often formed 1 to 2 orders of magnitude more slowly than their five-membered counterparts.…”

“…Computational chemistry as well as carefully constructed experiments have shed light on the underlying reasons for the trends observed for these group transfer reactions. [7][8][9][10][11][12] Other than the substitution at hydrogen, which would appear to "go around corners" because of the orbitals involved during homolytic substitution, for the remaining main group elements, the backside mechanism requires a collinear (or nearly so) arrangement of attacking and leaving radicals with deviations from this geometry resulting in unfavorable processes with high-energy transition states. For example, Wild showed that 1,4-, 1,5-, and 1,6-homolytic translocations of chlorine, bromine, and iodine have prohibitively high-energy barriers as determined by MP2/DZP calculations (Scheme 2) consistent with substantially "bent" transition state geometries at the halogen (120-145…”

“…However, unlike halogen, Wild was able to locate a second transition state for intramolecular homolytic substitution at sulfur and selenium, and that transition state led to the formation of the corresponding heterocycle. 8 Indeed, so unfavorable is intramolecular translocation at sulfur and selenium that even a hydrogen atom is calculated to prefer to leave, resulting in the formation of the heterocycle in preference to group transfer (Scheme 3)! So, here we have a fundamental difference between chalcogen and halogen: the second substituent on the chalcogen can act as a leaving group; indeed, it would appear to be easier to adopt the required "backside attack" orientation of attacking and leaving radicals during ring formation, than during translocation.…”

“…The story is slightly more complicated for reactions involving tellurium in that radical attack at tellurium mostly results in the formation of hypervalent intermediates; however, they are calculated to lie in very shallow wells on their respective potential energy surface and, as a consequence, behave in a similar manner to their sulfur and selenium counterparts in relation to the overall chemistry observed (Scheme 3). 8 Given these computational data, one might begin to imagine ways of engineering systems that would result in efficient ring formation and it is no surprise that many synthetically useful examples of this chemistry are carried out using stable radical leaving groups such as tert-butyl and benzyl.…”

Alkyl Radical Generation by an Intramolecular Homolytic Substitution Reaction between Iron(II) and Trialkylsulfonium Groups

“…[8] However, in this work we show that trialkylsulfonium species can easily be cleaved reductively via an intramolecular homolytic substitution reaction. [11,12] In accordance with Pryor's recommendation [13] we use the designation "S H 2" for homolytic, direct, one step displacement reactions with backside attack (1) in this paper. They are generally accepted to follow one of three possible mechanisms.…”