Direct Synthesis of N-Protected Serine- and Threonine-Derived Weinreb Amides via Diboronic Acid Anhydride-Catalyzed Dehydrative Amidation: Application to the Concise Synthesis of ­Garner’s Aldehyde

Abstract

An efficient method for the direct synthesis of Weinreb amides derived from serine and threonine derivatives via diboronic acid anhydride-catalyzed hydroxy-directed amidation is described. This is the first successful example of the synthesis of serine- or threonine-derived Weinreb amides using catalytic dehydrative amidations. The methodology could be applied to the concise synthesis of Garner’s aldehyde.

Chemistry and Biology of Acyloin Natural Products

“…4 The configurations of soraphinols A ( 1 ) and B ( 3 ) were eventually confirmed by synthesis. 11 12 Similarly, the absolute configuration of 2 has been confirmed by synthesis. 13 The stereochemistry of ( S )-sattabacin ( 5a ), 14 4-hydroxysattabacin ( 7 ), 6 14 actinopolymorphol A ( 8 ), 6 and sattazolin A ( 14 ) 15 have all been assigned by total synthesis.…”

“…The Shimada group 12 has recently developed a catalytic Weinreb amide formation from α-hydroxy acids and N , O -dimethylhydroxylamine using a diboronic acid anhydride (DBAA) type catalyst 96 . This method is the first example of a catalytic dehydrative amidation for the formation of Weinreb amides, culminating in the synthesis of eight acyloins, including the first total synthesis of soraphinol B ( 3 ) in a one-pot fashion, which served to confirm the absolute configuration.…”

Heteroelement Analogues of Benzoxaborole and Related Ring Expanded Systems

“…However, unlike benzoxadiboroles, the B-O-B linkage in 32 seems to be rather stable as there are no data which might indicate that a reversible hydrolysis to naphthalene-1,8-diboronic acid occurs to any appreciable extent. Compound 32 was used as a starting material for synthesis of a few 1H,3H-naphth[l,8-cd][l,2,6]oxadiborin derivatives (34)(35)(36)(37) where hydroxyl groups were replaced with OMe, Cl, Me [23], or mesityl (Mes) substituents [24], respectively. Very recently, a structurally extended analogue of 32 based on bicyclohexene-perinaphthalene framework 38 was obtained using an analogous protocol involving brominelithium exchange in an appropriate dibromide, followed by boronation.…”

“…Remarkably, 41-42 were reported as efficient catalysts of dehydrative amidation of carboxylic acids with amine substrates. Initially, they were employed for efficient preparation of various α-and β-hydroxy substituted amides [32] but thereafter also proved effective in catalyzing the formation of Weinreb amides [33,34] as well as various oligopeptides [35]. In the former case, the proposed mechanism of the catalytic process involves the cooperation of the two boron atoms in 41-42, which enables the formation of a cyclic mixed anhydride with carboxylic acid molecule, as evidenced by the ESI MS spectrum; this is followed by an attack of amine on the activated carbonyl group (Scheme 15) [32].…”

Expeditious Access to the B3NO2 Heterocycle Enabling Modular Derivatization

“…Since the pioneering report by Yamamoto et al revealing the specific utility of boronic acids for catalytically coupling carboxylic acids and amines without coproducing waste, a number of boronic acid derivatives and related boron-containing compounds have been reported. , The previous 5 years have witnessed the emergence of diboron compounds as superior catalysts to drive this transformation, an idea sparked by the detailed mechanistic study by Whiting and Ishihara delineating the involvement of oligomeric boron species in boronic acid catalysis (Figure ). − In 2017, our group disclosed a new molecular entity featuring a unique six-membered B 3 NO 2 heterocycle, DATB (1,3-dioxa-5-aza-2,4,6-triborinane), that exerts high catalytic efficiency in dehydrative amide bond-forming reactions with broad substrate generality …”