Reductive Coupling of Alkynes and Aldehydes

The challenges of these types of reactions are the control of the regio- (30 V5. 30 ), enantio- and P/Z-selectivity in the formation of the double bond. 

It is thought that in complex 32 the aldehyde-BEts adduct approaches the coordinated alkyne-Ni(0) complex in a way that the BEts group is away from the large ferrocenyl group (and syn to the small methyl group), eventually leading to oxametallacyclopentene intermediate 33. 

The coupling between 34 and 35 using tributylphosphine was completely nondiastereoselective. In contrast, using the depicted ferrocenylphosphine, the desired diastereomer (3 1 selectivity) and regiosiomer (2 1 selectivity) of 36 was 

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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). 

Ni-catalysed reductive coupling of alkynes and aldehydes in the presence of excess of reductant (triethylborane) forms a new C-C bond and provides allylic alcohols (Scheme 8.13), which are useful building blocks in organic synthesis. 

Scheme 8.14 Selected examples of reductive coupling of alkynes and aldehydes using P-stereogenic ferrocenylphosphines.

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

AUylic alcohols can also be accessed from the reductive coupling of allenes and aldehydes. As with the similar aldehyde-alkyne system, trialkylsilanes can be... 

Another effective catalyst system for intermolecular reductive coupling is the combination of Ni(COD)2/NHC with EtsSiH as a stoichiometric reducing agent (Scheme 8.21) [40]. The NHC catalyst is more reactive than analogous phosphine-based catalysts and a broad range of alkynes and aldehydes undergo reductive coupling under these conditions. 

Reductive nickel-catalysed couplings between alkynes and aldehydes provide ( )-trisubstituted allylic alcohols, a moiety found to possess significant biological effects. For this reason, reductive couplings have been used in the synthesis of natural products. An example, reported by Jamison and Chan, is given in Scheme 8.16. 

SCHEME 5.63 Ni(COD)-IMes-catalyzed reductive coupling of alkynes, aldehydes, and triethylsilanes. 

The special salt effect is a constant feature of the activation of substrates in cages subsequent to ET from electron-reservoir complexes. In the present case, the salt effect inhibits the C-H activation process [59], but in other cases, the result of the special effect can be favorable. For instance, when the reduction of a substrate is expected, one wishes to avoid the cage reaction with the sandwich. An example is the reduction of alkynes and of aldehydes or ketones [60], These reductions follow a pathway which is comparable to the one observed in the reaction with 02. In the absence of Na + PFg, coupling of the substrate with the sandwich is observed. Thus one equiv. Na+PFg is used to avoid this cage coupling and, in the presence of ethanol as a proton donor, hydrogenation is obtained (Scheme VII). 

Recently, it has been demonstrated that coordination vacancies on the surface metal cations are relevant to the unique redox reactivity of oxide surfaces]2]. Oxidation of fonnaldehyde and methyl formate to adsorbed formate intermediates on ZnO(OOOl) and reductive C-C coupling of aliphatic and aromatic aldehydes and cyclic ketones on 1102(001) surfaces reduced by Ar bombardment are observed in temperature-prognunmed desorption(TPD). The thermally reduced 1102(110) surface which is a less heavily damaged surface than that obtained by bombardment and contains Ti cations in the -t-3 and +4 states, still shows activity for the reductive coupling of formaldehyde to form ethene]13]. Interestingly, the catalytic cyclotrimerization of alkynes on TiO2(100) is also traced in UHV conditions, where cation coordination and oxidation states appear to be closely linked to activity and selectivity. The nonpolar Cu20( 111) surface shows a... 

A number of chiral monodentate phosphines have been examined in asymmetric nickel-catalyzed reductive couplings of aldehydes and alkynes. The best results to date have been obtained with (+)-NMDPP (16) [33]. Aromatic internal alkynes and branched aldehydes participate with excellent enantiose-lectivity (Scheme 15), although yields and enantioselectivities were somewhat lower with other combinations of aldehydes and alkynes. In a complemen-... 

A broad array of mechanistic pathways may be considered in the different variants of nickel-catalyzed reductive couplings of aldehydes and alkynes, and a generalized overview of possible mechanisms has been previously described [10]. Whereas a comprehensive mechanistic study has not been presented, a number of key observations have been illustrated that provide insight into how the nickel-catalyzed reductive couplings of aldehydes and alkynes proceed. It should be stressed at the outset that the different reaction variants may proceed by different mechanisms. 

The nickel-catalyzed reductive coupling of aldehydes and alkynes is only one member of a growing class of processes that involve the three-component addition of two rr-components and a reducing agent (Scheme 24). An... 

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