Aldehydes, coupling reagents

Cross pinacol coupling of aldehydes. Pedersen et al.2 have reported the first general method for stereoselective pinacol coupling of aldehydes by use of this vanadium(II) reagent. Aryl aldehydes couple in the presence of 1 to pinacols in >90% yield and with high diastereoselectivity (dllmeso = 12-100 1). Aliphatic aldehydes under similar conditions couple only slowly, but depending on the struc-... 

The formation of acetals from carbonyl compounds requires acid catalysis and (sometimes) the presence of water-coupling reagents (for instance, anhydrous CUSO4). The conversion of aliphatic aldehydes into dimethyl acetals slightly increases the retention parameters of analytes (ARI = 189 17). The cyclic ethylene derivatives (1,3-dioxolanes, ARI = 212 7, this value is valid only for acyclic carbonyl compounds) are more stable to the hydrolysis and used in GC practice... 

Other aldehyde-to-olefin coupling reagents of low-valent metals have also been described however, they suffer from being less efficient. The tungsten(III) alkox-... 

An auxiliary that has proven to function remarkably well, though, is the use of ephedrine to form a cyclic acceptor68. The cyclic dicarbonyl substrate is prepared from methyl hydrogen malonate and /-ephedrine hydrochloride using 2-chloro-l-methylpyridinium tosylate as coupling reagent. Knoevenagel condensation with an appropriate aldehyde affords, with few exceptions, the Z-isonier preferentially. 

Meutermans and Alewood [48] reported the solid-phase synthesis of tetrahydroisoquinolines 13 and dihydroisoquinolines 13a using the Bischler-Napieralski reaction (Fig. 5). The polystyrene resin-bound deprotected L-3,4-dimethoxyphenylalanine was acylated with acetic acid derivatives using N- [(IH-benzotriazol-1 -yl)(dimethylamino)methylene] -iV-methylmethana-minium hexafluorophosphate A-oxide (HBTU) as a coupling reagent. The product obtained was then treated with phosphorus oxychloride under optimized conditions to afford a Bischler-Napieralski cyclization. Hutchins and Chapman [49] reported the synthesis of tetrahydroisoquinolines 13b and 4,5,6,7-tetrahydro-3H-imidazol[4,5-c]pyridines 14 via cyclocondensation of the appropriate dipeptidomimetic with various aldehydes (Fig. 6). 

Poor purity was obtained for bulky R, groups such as phenyl or isopropyl however, excellent results were obtained with bromoacetic acid (Ri = H), 2-bromopropionic acid (Ri = Me), and 2-bromovaleric acid (Ri = Et). Following Fmoc removal with 20% piperidine in DMF, reductive alkylation of the free amine occurred in the presence of an aldehyde and sodium cyanoborohydrate (NaBHgCN). The formation of thiomorpholinone occurred via intramolecular amidation with HATU as the coupling reagent. 

Soon afterward, the same group accomplished the first asymmetric organo-SOMO a-vinylation of aldehydes using vinyl trifluoroborate salts (Scheme 8.30) [137]. Broad functional groups tolerance, high reaction efficiency, trawi-olefin selectivity, and enantioselectivity were obtained under optimized reaction conditions in the presence of imidazolidinone catalyst LXIV. Moreover, the steric demands of the aldehyde substrate have little influence on efficiency and enantiocontrol. This reported transformation also represents the first use of boron salts as coupling reagents for radical-based processes. 

The explosion in novel reactions catalyzed by NHCs began with the 2004 disclosure of the first internal redox reactions of a-functionalized aldehydes by NHCs. The Bode group reported the thiazolium-catalyzed conversion of a,p-epoxyaldehydes to p-hydroxyesters (Scheme 14.5). This reaction produced esters without the need for stoichiometric coupling reagents, and... 

Introduction. The principal synthetic application of 2-morpholinoethyl isocyanide is as a coupling reagent of amino acids to yield peptides. It also reacts with aldehydes or ketones to yield amides, with acids to yield imidazolinium salts, and has been used as a ligand in spectroscopic studies to examine shielding effects ... 

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