Intermolecular coupling reductions

Though several intermolecular catalytic reductive aldol additions are reported, corresponding reductive cyclizations have received less attention. The first reported reductive aldol cyclization involves use of a (diketonato)cobalt(ll) precatalyst in conjunction with PhSiHj as terminal reductant.48,486 The reductive cyclization is applicable to aromatic and heteroaromatic enone partners to form five- and six-membered rings. As demonstrated by the reductive cyclization of mono-enone mono-aldehyde 65a to afford aldol 65b, exceptionally high levels of ty -diastereoselectivity are observed. Interestingly, exposure of the substrate 65a to low-valent nickel in the presence of excess Et2Zn provides the isomeric homoaldol cyclization product 65c via reductive coupling to the enone /3-position (Scheme 43).47a... 

For selected reviews encompassing intra- and intermolecular direct reductive coupling of alkynes to carbonyl partners, see [151-158]... 

Intermolecular coupling between ketones and 0-methyl oximes, hydrazones and nitrones is achieved on reduction at a tin cathode in isopropanol [105]. It is not clear which of the reacting species accepts the initial electron in these processes. The reaction with 0-methyloximes, followed by catalytic reduction of the first formed O-methylhydroxylamine, is a convenient synthetic route to 2-amino-alcohols. 

Optically active chiral vicinal diamines are produced by Sml2-promoted reductive coupling of an imine derived from benzaldehyde and l-isopropyl-2-methoxyethylamine. Intermolecular coupling proceeds in a diastereoselective... 

The major reason for using transition-metal catalysts in the intermolecular coupling of aryl halides is to minimize the competition from further reduction of the radical formed by carbon-halogen bond cleavage of the radical anion. The competition from further reduction is less severe when a suitably proximate second aryl group is present, which may react... 

Intermolecular coupling of pyridines with ketones under acidic conditions has received attention but like the intramolecular reductive coupling of aromatic rings linked to aliphatic ketones [Eq. (62)], the reaction is essentially a ketone reduction, and the reader is referred to Chapter 10. 

Attempted intermolecular coupling of ketones and nitriles under conditions similar to those used for intramolecular coupling led to mixtures of two types of ketone-nitrile coupling products and alcohols resulting from ketone electroreduction. Product selectivity could be changed altering nitrile/solvent (2-propanol or ethanol) composition. Some results for cyclohexanone/acetonitrile reductions are shown in Scheme 27. 

The use of enals in nickel-promoted intermolecular couplings was initially limited to stoichiometric [3 -1- 2]/[2 + 1] cycloadditions [26], This limitation was overcome with the development of a Ni(COD)2/PCy3/R3SiH/THF reaction system, whereby the reductive coupling of alkynes and enals was achieved to afford a highly chemo- and stereo-selective synthesis of Z-enol silanes (Scheme 8.6) [27]. 

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