Reversibility and reactivity in an acid catalyzed cyclocondensation to give furanochromanes – a reaction at the ‘oxonium-Prins’ vs. ‘ortho-quinone methide cycloaddition’ mechanistic nexus

Abstract

Herein we report a combined experimental and computational investigation of the acid catalyzed cyclocondensation reaction between styrenyl homoallylic alcohols and salicylaldehyde to form furanochromanes.

Kinetic Analysis as an Optimization Tool for Catalytic Esterification with a Moisture-Tolerant Zirconium Complex

“…During the last decades, modern and user-friendly methods for intuitive visual kinetic analysis of organic reactions have been developed, starting with Blackmond’s pioneering reaction progress kinetic analysis (RPKA), and recently complemented with Burés’ variable time normalization analysis (VTNA) . These methodologies enable facile extraction of kinetic data by the utilization of full reaction profiles for a minimal number of experiments under synthetically relevant conditions to generate an in-depth understanding of a chemical system, and have been successfully employed for the mechanistic elucidation of a wide variety of organic transformations . While valuable from a fundamental perspective, mechanistic insights can also be converted into strategic modifications of reaction conditions to improve yields and selectivities .…”

Chiral Phosphoric-Acid-Catalyzed Cascade Prins Cyclization

“…We noted that an insightful investigation of the mechanism indicates that the diastereoselectivity (trans vs cis) of the Prins cyclization is dependent on the substrates and corresponding six-membered or five-membered transition states. , Thus we assumed a one-pot cascade process to access trans-fused THQs: Trans-fused oxygenated heterocycles could be obtained in the Prins cyclization and then delivered to the chiral THQs by sequential cyclization (Scheme b). The challenge associated with this hypothesis is the control of diastereo-/enantioselectivities in the Prins cyclization, which could be enabled by the design and utility of the advantaged six-membered transition state.…”

Asymmetric Brønsted Acid Catalyzed Cycloadditions of ortho-Quinone Methides and Related Compounds

“…Scheme 6 Intramolecular [4+2]-cycloaddition of salicylaldehydes 19 and dienyl homoallyl alcohols 20 and mechanistic considerations. 16,17 Highly valuable furanochromane products 21 carrying three contiguous chiral centers were formed with good yields, as single diastereomers and with exceptional enantioselectivities (Scheme 6). The substrate scope, however, appears to be limited as simple homoallyl alcohols lacking the additional double bond failed to give an enantioselective reaction.…”

“…Subsequent studies by Spivey and coworkers suggested that this cycloaddition may as well follow a stepwise Prins-like mechanism with a benzyl cation as discrete intermediate rather than a concerted cycloaddition. 17 The precise substrate structure and the exact reaction conditions appear to be responsible, which of the two reaction manifolds are operative.…”

“…Thus, List and Xie reacted salicylaldehydes 19 and dienyl homoallyl alcohols 20 in the presence of an imidodiphosphate catalyst (5 mol%) to produce the o-QM in situ, which in turn then engaged the appended dienophile in an oxa-Diels-Alder reaction (Scheme 6). 16 Scheme 6 Intramolecular [4+2]-cycloaddition of salicylaldehydes 19 and dienyl homoallyl alcohols 20 along with mechanistic considerations 16,17 Highly valuable furanochromane products 21 carrying three contiguous chiral centers were formed with good yields, as single diastereomers and with exceptional enantioselectivities (Scheme 6). The substrate scope, however, appeared to be limited as simple homoallyl alcohols lacking the additional double bond failed to give an enantioselective reaction.…”