The Emergence of Quinone Methides in Asymmetric Organocatalysis

Abstract

Quinone methides (QMs) are highly reactive compounds that have been defined as "elusive" intermediates, or even as a "synthetic enigma" in organic chemistry. Indeed, there were just a handful of examples of their utilization in catalytic asymmetric settings until some years ago. This review collects organocatalytic asymmetric reactions that employ QMs as substrates and intermediates, from the early examples, mostly based on stabilized QMs bearing specific substitution patterns, to more recent contributions, which have dramatically expanded the scope of QM chemistry. In fact, it was only very recently that the generation of QMs in situ through strategies compatible with organocatalytic methodologies has been realized. This tactic has finally opened the gate to the full exploitation of these unstable intermediates, leading to a series of remarkable disclosures. Several types of synthetically powerful asymmetric addition and cycloaddition reactions, applicable to a broad range of QMs, are now available.

Asymmetric Organocatalytic C‐C Bond Forming Reactions with Organoboron Compounds: A Mechanistic Survey

“…o ‐Quinone methides are novel and powerful motifs used in organic synthesis . ( R )‐3,3′‐dibromo‐BINOL ( R )‐ 49 was found to catalyze the addition of arylboronates as 48 to the benzylic position of ortho ‐quinone methide 47 to yield ortho substituted phenols 50 with er higher than 90:10 (Scheme ) .…”

Cooperative Catalysis for the Highly Diastereo‐ and Enantioselective [4+3]‐Cycloannulation of ortho‐Quinone Methides and Carbonyl Ylides

“…[9,10] Ortho-quinone methides (o-QMs) feature a particularly reactive 4p-system and have increasingly been exploited as versatile synthetic intermediates for the construction of complex heterocycles. [11] In recent years, we and others have meticulously developed Brønsted acid catalyzed reactions of o-QMs with a wide range of typically 2p-nucleophiles, leading to a broad range of benzannulated oxygen heterocycles with good to excellent stereocontrol. [12,13] We now report the first cooperative, catalytic, enantioselective [4+3]-cycloannulation of o-QMs and carbonyl ylides to afford complex and enantiomerically highly enriched oxabicyclic dibenzooxacines.…”

Asymmetric Synthesis of 2,3‐Dihydrobenzofurans by a [4+1] Annulation Between Ammonium Ylides and In Situ Generated o‐Quinone Methides

“…It has been reported that the introductiono fs terically demanding groups at this positionl eads to the preferred formation of the (Z)-quinone methides, whereas unsubstituted derivatives mainly form E isomers. [14] We thusr ationalised that this lower selectivity mayb ea ttributed to formation of al ess selective (Z)-quinone methide (or an E/Z mixture) in theset wo cases.…”

“…[4-6, 12, 13] One particularly powerful methodology for the generation of carbo-and heterocyclic targets through [4+ +n]a nnulation approaches relies on the use of in situ generated o-quinone methides or analogousa za-o-quinonem ethides. [14,15] Recently, the first example of the use of in situ generated o-quinone methides 3 (precursor 1)f or [4+ +1] annulation reactions with in situ generated carbonyl-stabilised sulfur ylides 4 (obtained from sulfonium salts 2)t oa ccess 2,3-dihydrobenzofurans 5 was reported by Zhou and co-workers( Scheme 1). [5a] High yields and excellent diastereoselectivities were obtained fordifferent carbonyl-stabiliseds ulfur ylides.…”