Relative reactivity of alkenyl alcohols in the palladium-catalyzed redox-relay Heck reaction

The relative rates of alkenyl alcohols in the Pd-catalyzed redox-relay Heck reaction were measured in order to examine the effect of their steric and electronic properties on the rate-determining step. Competition experiments between an allylic alkenyl alcohol and two substrates with differing chain lengths revealed that the allylic alcohol reacts 3–4 times faster in either case. Competition between di- and trisubstituted alkenyl alcohols provided an interesting scenario, in which the disubstituted alkene was consumed first followed by reaction of the trisubstituted alkene. Consistent with this observation, the transition structures for the migratory insertion of the aryl group into the di- and trisubstituted alkenes were calculated with a lower barrier for the former. An internal competition between a substrate containing two alcohols with differing chain lengths demonstrated the catalyst's preference for migrating toward the closest alcohol. Additionally, it was observed that increasing the electron-density in the arene boronic acid promotes a faster reaction, which correlates with Hammett [sigma-rho] values to give a [rho] of −0.87

Palladium(II)-Catalyzed Enantioselective Aerobic Dialkoxylation of 2-Propenyl Phenols: A Pronounced Effect of Copper Additives on Enantioselectivity

A direct O2-coupled Pd(II)-catalyzed enantioselective dialkoxylation of 2-propenylphenols has been developed by utilizing chiral quinoline oxazoline ligands. A detrimental effect of added copper salts on enantioselectivity was observed which is attributed to the displacement of the chiral ligand off of Pd(II)

Palladium-Catalyzed Hydroarylation of 1,3-Dienes with Boronic Esters via Reductive Formation of π-Allyl Palladium Intermediates under Oxidative Conditions

A palladium-catalyzed reductive cross-coupling of 1,3-dienes with boronic esters in which a π-allyl Pd species is generated directly from a 1,3-diene via a Pd-catalyzed aerobic alcohol oxidation is reported. Both the scope of the process and the origin of a highly selective 1,2-addition are discussed

Design of Hydrogen Bond Catalysts Based on a Modular Oxazoline Template: Application to an Enantioselective Hetero Diels−Alder Reaction

A catalyst system that displays two hydrogen bond donating arms from a rigid oxazoline backbone and its utility in a hydrogen bond promoted enantioselective hetero Diels−Alder reaction are described

Modular Synthesis of Amine-Functionalized Oxazolines

Substituted oxazoline amines have been prepared in high yield from β-amino alcohols and Fmoc-protected α-amino acids using CCl4, PPh3, and Hünig's base in a one-pot procedure followed by base-mediated deprotection

Palladium-Catalyzed 1,1-Difunctionalization of Ethylene

The 1,1-difunctionalization of ethylene, with aryl/vinyl/heteroaryl transmetalating agents and vinyl electrophiles, is reported. The reaction is high-yielding under a low pressure of ethylene, and regioselectivity is generally high for the 1,1-disubstituted product. The process is highlighted by the use of heteroaromatic cross-coupling reagents, which have not been competent reaction partners in previously reported efforts

Modular Synthesis of Amine-Functionalized Oxazolines

Substituted oxazoline amines have been prepared in high yield from β-amino alcohols and Fmoc-protected α-amino acids using CCl4, PPh3, and Hünig's base in a one-pot procedure followed by base-mediated deprotection

Palladium-Catalyzed Enantioselective Relay Heck Arylation of Enelactams: Accessing α,β-Unsaturated δ‑Lactams

In this Communication, we describe the construction of chiral α,β-unsaturated δ-lactams, widely used as pharmacophores, in high yields and excellent enantio­selectivities using an oxidative relay Heck arylation reaction. This strategy also allows facile access to 7-substituted α,β-unsaturated ε-lactam products and δ-lactams containing a tetrasubstituted nitrogen-bearing stereocenter

Development of a General Pd(II)-Catalyzed Intermolecular Hydroalkoxylation Reaction of Vinylphenols by Using a Sacrificial Alcohol as the Hydride Source

A general hydroalkoxylation of vinylphenols has been successfully developed wherein primary, secondary, and tertiary alcohols can be used as nucleophiles. The key conceptual breakthrough is the use of sec-phenethyl alcohol at relatively low concentrations as the sacrificial alcohol to undergo oxidation and provide the proposed Pd−H intermediate

Steric Effects in the Aerobic Oxidation of π-Allylnickel(II) Complexes with <i>N</i>-Heterocyclic Carbenes

π-Allylchloro(NHC)nickel(II) complexes were synthesized and their reactions with O2 were studied. Ligand steric effects were found to determine the difference between rapid oxidation of the allyl group to produce bis-μ-hydroxonickel complexes and no observable reaction. The ability of the metal−NHC bond to rotate correlates with the ability of the complex to react with O2. In the limiting cases, conformationally restricted complexes are stable to O2 and complexes with rapid Ni−NHC bond rotation react rapidly with O2. Complexes with intermediate conformational flexibility were found to exhibit lesser reactivity with O2. On the basis of the observed inertness of complexes with saddle-shaped ligands to O2, we propose the adoption of a nonplanar geometry upon reaction with O2 to be required. The issue of conformational flexibility versus rigidity is expected to directly impact the catalytic behavior of metal−NHC complexes