Radical cyclization of epoxyketones via a 1,5-Bun 3Sn group or a 1,5-H atom transfer

Kim, Sunggak; Koh, Jae Suk

doi:10.1039/c39920001377

Cited by 32 publications

(7 citation statements)

References 12 publications

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“…[21] Radical-induced epoxide opening was used for the isomerization of a,b-epoxyketones to carbocycles (Scheme 1B). [22] As ubsequent 1,5-H shift would give the isomeric alkoxy radical IM2, [23] which would undergo intramolecular addition to the double bond in a6-exo manner.T he resulting tertiary radical PD would undergo one electron oxidation to give atertiary cation, [24][25][26][27][28] which would be trapped by the terthydroxy group,furnishing the A/B rings (Scheme 1A,path a).…”

Section: Resultsmentioning

confidence: 99%

Biosynthesis of Indole Diterpene Lolitrems: Radical‐Induced Cyclization of an Epoxyalcohol Affording a Characteristic Lolitremane Skeleton

et al. 2020

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Lolitrems are tremorgenic indole diterpenes that exhibit a unique 5/6 bicyclic system of the indole moiety. Although genetic analysis has indicated that the prenyltransferase LtmE and the cytochrome P450 LtmJ are involved in the construction of this unique structure, the detailed mechanism remains to be elucidated. Herein, we report the reconstitution of the biosynthetic pathway for lolitrems employing a recently established genome‐editing technique for the expression host Aspergillus oryzae. Heterologous expression and bioconversion of the various intermediates revealed that LtmJ catalyzes multistep oxidation to furnish the lolitrem core. We also isolated the key reaction intermediate with an epoxyalcohol moiety. This observation allowed us to establish the mechanism of radical‐induced cyclization, which was firmly supported by density functional theory calculations and a model experiment with a synthetic analogue.

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Section: Resultsmentioning

confidence: 99%

Biosynthesis of Indole Diterpene Lolitrems: Radical‐Induced Cyclization of an Epoxyalcohol Affording a Characteristic Lolitremane Skeleton

et al. 2020

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“…9 In addition to several reports involving 1,2-silyl and germyl shifts, 10 intramolecular homolytic group transfers involving silicon, germanium, and tin have been put to good use by Davies and co-workers 11 as well as by Kim and his associates (Scheme 2). 12 There also appear to be several early reports of 1,2 migrations of halogen, 13 the Nesmeyanov rearrangement 14 (1,2-migration of chlorine) typifying the chemistry in question. Despite the appearance of rearranged products in these transforma- tions, there is still some considerable ambiguity concerning the reaction mechanism, namely, concerted migration versus a process involving dissociation followed by recombination.…”

Section: Introductionmentioning

confidence: 99%

Intramolecular Homolytic Translocation Chemistry: An ab Initio Study of 1,n-Halogen Atom Transfer Reactions in Some ω-Haloalkyl Radicals

Schiesser

Wild

1998

J. Org. Chem.

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Ab initio calculations using all-electron (3-21G(()()), 6-311G) and pseudopotential (DZP) basis sets, with (MP2, QCISD) and without (UHF) the inclusion of electron correlation, predict that 1,n-halogen transfer reactions in the 5-halo-1-pentyl (6), 6-halo-1-hexyl (7), and 7-halo-1-heptyl radicals (8) proceed via C(s)- and/or C(2)-symmetric transition states (9-11), except for the 5-bromo-1-pentyl (6, X = Br) radical for which a C(s)-symmetric transition state (9) was located only at the UHF/3-21G(()()) level of theory and the 5-iodo-1-pentyl radical (6, X = I) for which no transition state (9) could be located at any level of theory used in this study. Energy barriers for these translocation reactions of between 120.0 (1,7-iodine transfer) and 191.0 kJ mol(-)(1) (1,5-chlorine transfer) are predicted at the MP2/DZP level of theory; QCISD/DZP (single-point) calculations predict similar energy barriers. These high energy barriers are a consequence of unfavorable factors associated with ring size and long carbon-halogen separations in transition states (9-11) which lead to significant deviations from the collinear arrangement of attacking and leaving radicals preferred in transition states involved in homolytic substitution reactions at halogen. The dependence of transition state energy on attack angle at halogen has been explored for the attack of methyl radical at chloromethane. At the MP2/DZP level of theory, attack angles of between 80 and 90 degrees are calculated to lead to increases in energy barrier of about 100 kJ mol(-)(1) when compared with the collinear (180 degrees ) arrangement of attacking and leaving groups. The mechanistic implications of these predictions are discussed.

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“…Intramolecular translocation chemistry in molecules containing halo, phenylthio, trialkylsilyl, germyl, and stannyl moieties is representative of a homolytic substitution process in which the attacking and leaving radical form part of the same molecule . In addition to several reports involving 1,2-silyl and germyl shifts, intramolecular homolytic group transfers involving silicon, germanium, and tin have been put to good use by Davies and co-workers as well as by Kim and his associates the Nesmeyanov rearrangement typifying this chemistry.…”

Section: Introductionmentioning

confidence: 99%

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

Schiesser

Wild

1999

J. Org. Chem.

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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.

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Radical cyclization of epoxyketones via a 1,5-Bun 3Sn group or a 1,5-H atom transfer

Cited by 32 publications

References 12 publications

Biosynthesis of Indole Diterpene Lolitrems: Radical‐Induced Cyclization of an Epoxyalcohol Affording a Characteristic Lolitremane Skeleton

Biosynthesis of Indole Diterpene Lolitrems: Radical‐Induced Cyclization of an Epoxyalcohol Affording a Characteristic Lolitremane Skeleton

Intramolecular Homolytic Translocation Chemistry: An ab Initio Study of 1,n-Halogen Atom Transfer Reactions in Some ω-Haloalkyl Radicals

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

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