Evans Enolates: Structures and Mechanisms Underlying the Aldol Addition of Oxazolidinone-Derived Boron Enolates

Abstract

The soft enolization of an acylated oxazolidinone using di-n-butylboron triflate (n-Bu2BOTf) and trialkylamines and subsequent aldol addition was probed structurally and mechanistically using a combination of IR and NMR spectroscopies. None of the species along the reaction coordinate shows a penchant for aggregating. Complexation of the acylated oxazolidinone by n-Bu2BOTf was too rapid to monitor, as was the subsequent enolization with Et3N (triethylamine). The pre-formed n-Bu2BOTf·Et3N complex displaying muted Lewis acidity and affiliated tractable rates reveals a rate-limiting complexation via a transition structure with a complicated counterion. n-Bu2BOTf·i-Bu3N bearing a hindered amine shifts the rate-limiting step to proton transfer. Rate studies show that the aldol addition with isobutyraldehyde occurs as proffered by others.

Stereodivergent approach in the protected glycal synthesis of L-vancosamine, L-saccharosamine, L-daunosamine and L-ristosamine involving a ring-closing metathesis step

“…Synthesis of vancosamine and saccharosamine glycals. The chiral (−)-lactic methyl ester was identified as the privileged starting material considering that the Evans aldol reaction via boron enolates [ 26 – 28 ] with an appropriately O-protected aldehyde should afford the desired aldol adduct with a syn relative configuration between the two newly created chiral centers [ 29 – 30 ]. Moreover, the boron-mediated stereoselective aldol reaction is all the more interesting for our synthetic plan as stereochemical diversity can be generated depending on the absolute configuration of the chiral auxiliary used.…”

Use of chiral auxiliaries in the asymmetric synthesis of biologically active compounds: A review

“…Recent studies have attempted to shed light on the mechanistic aspects of Evans' aldol additions mediated by boron enolates. Zhang and Collum used a combination of infrared and NMR spectroscopies to examine structurally and mechanistically the soft enolization of an acylated oxazolidinone with di‐ n ‐butylboron triflate ( n ‐Bu 2 BOTf) and trialkylamines and the subsequent aldol addition reaction. None of the species along the reaction coordinate showed a tendency to aggregate.…”

“…The most surprising aspect of this reaction is the complexation mechanism and the unusual organoboron coordination chemistry discovered from it (Scheme ). Perhaps, the most valuable contribution of Zhang and Collum's work is the insight that trialkylamines play a dual role in boron enolate‐based Evans' aldol additions, acting as inhibitors/complexants of both Lewis acids and Brønsted bases. Hypothesizing that, via this approach, boron enolates could be used to optimize Cα quaternizations, the authors prepared complex 99 from isobutyryl derivative 98 using Et 3 N to shift the equilibrium from enolate 100 to 98 .…”

Pyridylic anions are soft nucleophiles in the palladium-catalyzed C(sp3)–H allylation of 4-alkylpyridines

“…Here we report a new mechanistic framework for C(sp 3 )–H allylation of pyridines, which exploits their metal-free soft-enolization 15 to form alkylidene dihydropyridines 16 (ADHPs) as semi-stable intermediates that are primed for a palladium-catalyzed decarboxylative allylation reaction ( Fig. 1d ).…”