Aldehydes simple couplings

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 inter molecular nickel-catalyzed reductive coupling of aldehydes and alkynes has largely been examined with the reaction variants involving either EtaB with monodentate phosphines [22] or EtaSiH with NHCs [21]. Substantial advances in simple couplings, large fragment couplings, diastereoselective variants, directed processes, and asymmetric variants have been made and are detailed below. 

An important biological process is the basis for a general coupling method of aldehydes into symmetncal acyloins, such as BETYROIN. The key catalyst is 5-(2-hydroxyethyl)-4-methyl-l,3-thiazole, an analog of thiamin. Condensation of ketones and aldehydes with excess acetonitrile can be accomplished in a simple way to produce a,p-unsaturated nitriles Cyclohexanone leads to CY-CLOHEXYLIDENEACETONITRILE while benzaldehyde gives CINNA-MONITRILE. 

Nitroalkenes are shown to be effective Michael acceptor B units in three sequential reactions (A + B + C coupling) in one reaction vessel. The sequence is initiated by enolate nucleophiles (A) and is terminated by aldehydes or acrylate electrophiles (C). The utility of this protocol is for rapid assembly of complex structures from simple and readily available components. A short total synthesis of a pyrrolizidine alkaloid is presented in Scheme 10.16.114... 

Silastannative coupling of 1,3-diene and aldehydes is achieved both in inter- and intramolecular fashions (Equations (116) and (117)).277 Interestingly, the reaction is catalyzed by nickel(0) complexes, whereas a platinum complex is used for simple 1,4-silastannation of 1,3-diene.278... 

The highest efficiency for probe attachment was found for the reaction of carboxylated probe with an aminosilane surface. However, the level obtained by simple adsorption (without the addition of ED AC) was equally as high (mean probe density = 600 to 700 fmoles/cm ). Conversely, the attachment of an amine-modified probe to a carboxyl surface was much less efficient (mean probe density = 300 fmoles/cm ). The least efficient coupling was obtained using aldehyde surfaces (mean probe density = 150 fmole/cm ). 

Dauben s group utilized the same retrosynthetic disconnections, but chose to add more functionality to the cycloaddition precursor. From a simple frawi-disubstituted cyclopentane, Dauben used an aldol reaction of a cyclopropylvinyl aldehyde to prepare the cycloaddition precursor. The diazo-substituted (3-ketoester was completed using a Roskamp-Padwa coupling followed by diazo-transfer. Addition of rhodium acetate to the diazo substituted p-ketoester 179 led to an excellent 86% yield of the correct diastereomer (Scheme 4.42). 

In 1977, an article from the authors laboratories [9] reported an TiCV mediated coupling reaction of 1-alkoxy-l-siloxy-cyclopropane with aldehydes (Scheme 1), in which the intermediate formation of a titanium homoenolate (path b) was postulated instead of a then-more-likely Friedel-Crafts-like mechanism (path a). This finding some years later led to the isolation of the first stable metal homoenolate [10] that exhibits considerable nucleophilic reactivity toward (external) electrophiles. Although the metal-carbon bond in this titanium complex is essentially covalent, such titanium species underwent ready nucleophilic addition onto carbonyl compounds to give 4-hydroxy esters in good yield. Since then a number of characterizable metal homoenolates have been prepared from siloxycyclopropanes [11], The repertoire of metal homoenolate reactions now covers most of the standard reaction types ranging from simple... 

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