Mechanism Of The Asymmetric Dehydrative Allylative Cyclization Of Alcohols To Cyclic Ethers Catalyzed By A Cpru Complex Of The Chiral Picolinic Acid-Type Ligand, Cl-Naph-Pycooh: Is A Pi-Allyl Intermediate Present?

Ru(II)Cp((R)-Cl-Naph-PyCOOH)]PF6 ((R)-1) catalyzes the dehydrative cyclization of (E)-hept-2-ene-1,7-diol (2) to 2-vinyltetrahydro-2H-pyran (3) with a 97:3 S/R enantiomer ratio. Complex (R)-1 is in equilibrium between two diastereomers (R,R-Ru)- 1 (A(R)) and (R,S-Ru)-1 (A(S)). A difference of turn over efficiency between the A(S) and A(R) cycles is thought to be the origin of the high enantioselectivity. The A(S) gives a major enantiomeric product (S)-3, according to the results of detailed mechanistic investigation via i) X-ray crystallographic analysis of related complexes, ii) NMR experiments using allylic alcohol 2, OH-lacking 2-mimic 4, d-labeled (S)-4-1d, enantiomerically enriched hept-6-ene-1,5-diol (6) as branched isomer of 2, and OH-lacking 6-mimic 5, iii) substrate structure/reactivity and selectivity relationships, iv) deuterium-labeling experiment, v) kinetics via calorimetric analysis, and vi) ligand structure/reactivity and selectivity relationships. A(S) captures 2 via hydrogen and halogen bonds. Oxidative addition in an H2Oin mode leads to a macrocyclic sigma-allyl intermediate. Here, an efficient n(C(7)OH)/pi*(C(3)=C(2)) trans-annular (TA) interaction facilitates an S(N)2' nucleophilic addition of OH in an OHTA manner to furnish (S)-3. Contrary to the A(S), A(R) cannot capture 2 using the halogen bond and slowly operates to give (R)-3. A conventional pi-allyl-complex-involved mechanism is ruled out by a contradiction in the result of ii) and iii).