Coupling of Alkynes with Aldehydes

Three-Component Couplings via Alkyl Croup Transfer-Method Development 

Reductive Couplings via Hydrogen Atom Transfer-Method Development 

The field of nickel-catalyzed reductive couplings has seen substantial interest in the past decade and numerous advances have been made in the area. There now exist several protocols, including simple aldehyde/alkyne coupling, diastereoselec-tive variants using transfer of chirality, asymmetric variants using either chiral 

The first nickel-catalyzed intermolecular reductive coupling utilized the combination of COD-stabilized zero-valent nickel, monodentate phosphine ligands, and 

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Scheme 5.1-27 The zinc triflate-catalyzed coupling of alkynes with aldehydes to give propargyl alcohols in an ionic liquid.

The inter- and intramolecular catalytic reductive couplings of alkynes and aldehydes recently have experienced rapid growth and are the topic of several recent reviews.5 h-8k 107 With respect to early transition metal catalysts, there exists a single example of the catalytic reductive cyclization of an acetylenic aldehyde, which involves the titanocene-catalyzed conversion of 77a to ethylidene cyclopentane 77b mediated by (EtO)3SiH.80 This process is restricted to terminally substituted alkyne partners (Scheme 53). 

Anhydrous iron(III) halides catalyse coupling of alkynes and aldehydes.211 Simple terminal alkynes, R CH, react with aldehydes, R2CHO, to give ( ,Z)-1,5-dihalo-1,4-dienes (55). In contrast, non-terminal arylalkynes give ( ,)-o, /3-unsaturated ketones. The catalysts also promote standard Prins cyclization of homoallylic alcohols. Studies of intermediates and of alkyne hydration - together with calculations - all support FeX3 complex formation with alkyne as the activating step. 

Scheme 3.25 Reductive coupling of alkynes and aldehydes with an N-heterocyclic carbene ligand.

Alkynes can also be coupled with allylic alcohols however, the reaction mechanism and therefore also the structure of products depends on the catalysts used. The first process is the coupling of alkynes with allylic alcohols to produce the y,<5-unsaturated ketones and aldehydes 131 and 132 (Scheme 57). The second process is reconstitutive addition of allylic alcohols to terminal alkynes to give the y,<5-unsaturated ketones 133 (Scheme 58). 

The participation of complex substrates was illustrated in an elegant total synthesis of (-)-terpestacin (Scheme 8) [24,25]. Coupling of alkyne 12 and aldehyde 13 with Ni(COD)2, phosphine 14, and Et3B afforded product 15 as a 2.6 1 mixture of regioisomers, and a 2 1 diastereoselectivity in a combined 85% yield. Whereas alkynes that possess two aliphatic substituents generally... 

Coupling of Alkynes or Allenes With Aldehydes and Ketones... 

An original, and versatile route toward ulosonic acids has been recently elaborated by Wu et al. [103,104,105], It based on a simple introduction of a-keto acid moiety via propargylation of suitable monosaccharides derived aldehydes and subsequent oxidation of the terminal alkynes. As it is exemplified by preparation of KDO, coupling of 61 with 3-bromopropyne gave the a fr-adduct 139 (Scheme 30). Its bromination using NBS/AgNC>3 provided the bromoalkyne 140, which on reaction with KMnC>4 afforded the desired a-keto acid ester, easily convertible into the anomeric mixture of KDO derivatives 143. The yield of all intermediates were very high. 

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