Structure–reactivity relationship for alcohol oxidations via hydride transfer to a carbocationic oxidizing agent

Abstract

Second‐order rate constants were determined for the oxidation of 27 alcohols (R1R2CHOH) by a carbocationic oxidizing agent, 9‐phenylxanthylium ion, in acetontrile at 60 °C. Alcohols include open‐chain alkyl, cycloalkyl, and unsaturated alcohols. Kinetic isotope effects for the reaction of 1‐phenylethanol were determined at three H/D positions of the alcohol (KIEα‐D = 3.9, KIEβ‐D3 = 1.03, KIEOD = 1.10). These KIE results are consistent with those we previously reported for the 2‐propanol reaction, suggesting that these reactions follow a hydride‐proton sequential transfer mechanism that involves a rate‐limiting formation of the α‐hydroxy carbocation intermediate. Structure–reactivity relationship for alcohol oxidations was deeply discussed on the basis of the observed structural effects on the formation of the carbocationic transition state (Cδ+OH). Efficiencies of alcohol oxidations are largely dependent upon the alcohol structures. Steric hindrance effect and ring strain relief effect win over the electronic effect in determining the rates of the oxidations of open‐chain alkyl and cycloalkyl alcohols. Unhindered secondary alkyl alcohols would be selectively oxidized in the presence of primary and hindered secondary alkyl alcohols. Strained C7C11 cycloalkyl alcohols react faster than cyclohexyl alcohol, whereas the strained C5 and C12 alcohols react slower. Aromatic alcohols would be efficiently and selectively oxidized in the presence of aliphatic alcohols of comparable steric requirements. This structure–reactivity relationship for alcohol oxidations via hydride‐transfer mechanism is hoped to provide a useful guidance for the selective oxidation of certain alcohol functional groups in organic synthesis. Copyright © 2011 John Wiley & Sons, Ltd.

Lewis Acid Catalyzed Reductive Cyclization of 2‐Aryloxybenzaldehydes and 2‐(Arylthio)benzaldehydes to Unsubstituted 9H‐Xanthenes and Thioxanthenes in Diisopropyl Ether

“…The reductive cyclization of 1 d also occurs in dry isopropanol to furnish xanthene 3 d in good yield (Scheme 8b). These results support the reduction of xanthylium ion 12 via hydride transfer from isopropanol and are in complete agreement with literature report [18b] . The cyclic alcohol 2 d could be synthesized in two steps [15d,22] and when subjected to the standard conditions provided xanthene 3 d within very short time (10 min) in 79% yield (Scheme 8c).…”

Computational Replication of the Abnormal Secondary Kinetic Isotope Effects in a Hydride Transfer Reaction in Solution with a Motion Assisted H-Tunneling Model

“… 29 These hydride transfer processes strictly follow the second-order kinetics and are thus proper systems to study the relationship between the magnitude of 2° KIEs and 1° H-tunneling. 29 − 32 The 2° KIEs on both the β-CH 3 /CD 3 position of the 2-propanol (β-D 6 2° KIE = 1.05) and on the α-9-H/D position of the Xn + (α-D 2° KIE = 0.99) (Scheme 1 , R = R′ = CH 3 , R″ = H) were found to be very close to unity and far from the corresponding EIEs (1.52 and 0.89, respectively). 29 They are expected to be closer to the corresponding EIEs, though, since Hammond’s Postulate predicts a late TS for such reactions that produce a highly unstable α-hydroxy carbocation product (C + –OH).…”

Imbalanced tunneling ready states in alcohol dehydrogenase model reactions: rehybridization lags behind H-tunneling

“…[24][25][26][27] Here, kinetics of the hydride-transfer reactions from alcohols to Xn + ClO 4 À in MeCN were similarly determined by following the decay of the Xn + UV-Vis absorption (Fig. S1, ESIw).…”