123751-66-6Relevant academic research and scientific papers
Mechanism, reactivity, and selectivity in palladium-catalyzed redox-relay heck arylations of alkenyl alcohols
Xu, Liping,Hilton, Margaret J.,Zhang, Xinhao,Norrby, Per-Ola,Wu, Yun-Dong,Sigman, Matthew S.,Wiest, Olaf
supporting information, p. 1960 - 1967 (2014/03/21)
The enantioselective Pd-catalyzed redox-relay Heck arylation of acyclic alkenyl alcohols allows access to various useful chiral building blocks from simple olefinic substrates. Mechanistically, after the initial migratory insertion, a succession of β-hydride elimination and migratory insertion steps yields a saturated carbonyl product instead of the more general Heck product, an unsaturated alcohol. Here, we investigate the reaction mechanism, including the relay function, yielding the final carbonyl group transformation. M06 calculations predict a ΔΔGa of 1 kcal/mol for the site selectivity and 2.5 kcal/mol for the enantioselectivity, in quantitative agreement with experimental results. The site selectivity is controlled by a remote electronic effect, where the developing polarization of the alkene in the migratory insertion transition state is stabilized by the C-O dipole of the alcohol moiety. The enantioselectivity is controlled by steric repulsion between the oxazoline substituent and the alcohol-bearing alkene substituent. The relay efficiency is due to an unusually smooth potential energy surface without high barriers, where the hydroxyalkyl-palladium species acts as a thermodynamic sink, driving the reaction toward the carbonyl product. Computational predictions of the relative reactivity and selectivity of the double bond isomers are validated experimentally.
Enantioselective redox-relay oxidative heck arylations of acyclic alkenyl alcohols using boronic acids
Mei, Tian-Sheng,Werner, Erik W.,Burckle, Alexander J.,Sigman, Matthew S.
supporting information, p. 6830 - 6833 (2013/06/05)
A general, highly selective asymmetric redox-relay oxidative Heck reaction using achiral or racemic acyclic alkenols and boronic acid derivatives is reported. This reaction delivers remotely functionalized arylated carbonyl products from acyclic alkenol substrates, with excellent enantioselectivity under mild conditions, bearing a range of useful functionality. A preliminary mechanistic investigation suggests that the regioselectivity of the initial migratory insertion is highly dependent on the electronic nature of the boronic acid and more subtle electronic effects of the alkenyl alcohol.
Synthesis and Antifolate Properties of 10-Alkyl-5,10-dideaza Analogues of Methotrexate and Tetrahydrofolic Acid
DeGraw, Joseph I.,Christie, Pamela H.,Kisliuk, Roy L.,Gaumont, Yvette,Sirotnak, Francis M.
, p. 673 - 677 (2007/10/02)
Synthesis of the 10-methyl and 10-ethyl analogues of 5,10-dideazatetrahydrofolic acid (DDTHF), a potent inhibitor of glycinamide ribotide (GAR) formyltransferase, is reported.Key intermediates in the process were 10-methyl- and 10-ethyl-4-amino-4-deoxy-5,
