A Chiral Picolinic Acid Ligand, Cl-Naph-PyCOOH, for CpRu-Catalyzed Dehydrative Allylation: Design, Synthesis, and Properties

Abstract

Abstract A CpRu/Brønsted acid-combined catalyst, CpRu(II)/picolinic acid (PyCOOH), acts as an efficient catalyst for the allyl protection/deprotection of alcohols. This discovery has resulted in the development of a new axially chiral ligand, Cl-Naph-PyCOOH (2a; 6-(2-chloronaphthalen-1-yl)-5-methylpyridine-2-carboxylic acid) through an investigation on the ligand structure-reactivity relationship in the CpRu-catalyzed dehydrative cyclization of (E)-hept-2-ene-1,7-diol (5) to 2-vinyltetrahydro-2H-pyran (6). A large-scale synthetic procedure for 2a and the allyl esters 2b has been established. The activation energy ΔG‡ of the stereoinversion and the half-life time of (R)-2b racemization have been determined to be 33.7 kcal mol−1 and 16,000 years at 25 °C, respectively. The CpRu(II)/(R)-Cl-Naph-PyCOOH catalyst exists as a 1:1 diastereomeric mixture of (R,RRu)-3 (AR) and (R,SRu)-3 (AS) because of the axial chirality of 2a and the Ru stereogenic center. The epimerization rate of the Ru center is 19.5 s−1 at 30 °C with an energy barrier ΔG‡ of 16.0 kcal mol−1. Both AR and AS have their own reactivity and enantioselectivity. Nevertheless, an enantiomer ratio of up to >99:1 can be realized in the allylative cyclization of E-allylic alcohols possessing a protic nucleophile, OH, NHCOR, NHSO2R, or COOH, at the terminal position. Questions about the mechanism have been raised as progress is being made towards a mechanistic investigation.