Aldol reactions metal hydrides

After the initial two reports of Rh- and Co-catalyzed reductive aldol couplings, further studies did not appear in the literature until the late 1990s. Beyond 1998, several stereoselective and enantioselective reductive aldol reactions were developed, which are catalyzed by a remarkably diverse range of metal complexes, including those based upon Pd, Cu, Ir, and In. In this chapter, transition metal-catalyzed aldol, Michael, and Mannich reactions that proceed via transition metal hydride-promoted conjugate reduction are reviewed. 

The mechanism of the catalytic cycle is outlined in Scheme 1.37 [11]. It involves the formation of a reactive 16-electron tricarbonyliron species by coordination of allyl alcohol to pentacarbonyliron and sequential loss of two carbon monoxide ligands. Oxidative addition to a Jt-allyl hydride complex with iron in the oxidation state +2, followed by reductive elimination, affords an alkene-tricarbonyliron complex. As a result of the [1, 3]-hydride shift the allyl alcohol has been converted to an enol, which is released and the catalytically active tricarbonyliron species is regenerated. This example demonstrates that oxidation and reduction steps can be merged to a one-pot procedure by transferring them into oxidative addition and reductive elimination using the transition metal as a reversible switch. Recently, this reaction has been integrated into a tandem isomerization-aldolization reaction which was applied to the synthesis of indanones and indenones [81] and for the transformation of vinylic furanoses into cydopentenones [82]. 

The starting material for the present synthesis was Wieland-Miescher ketone (24), which was converted to the known alcohol (25) by the published procedure [10], Tetrahydropyranylation of alcohol (25) followed by hydroboration-oxidation afforded the alcohol (26), which on oxidation produced ketone (27). Reduction of (27) with metal hydride gave the alcohol (28) (56%). This in cyclohexane solution on irradiation with lead tetraacetate and iodine produced the cyclic ether that was oxidized to obtain the keto-ether (29). Subjection of the keto-ether (29) to three sequential reactions (formylation, Michael addition with methyl vinyl ketone and intramolecular aldol condensation) provided tricyclic ether (30) whose NMR spectrum showed it to be a mixture of C-10 epimers. The completion of the synthesis of pisiferic acid (1) did not require the separation of epimers and thus the tricyclic ether (30) was used for the next step. The conversion of (30) to tricyclic phenol (31) was... 

Because of their tendency to undergo aldol reactions, various conditions have been investigated to develop methods for the sulfenylation of aldehydes. Indirect methods involving metallation of the corresponding imines (10 Scheme 11 ) offer a preferred alternative to the low temperature direct sulfenylation described above, but better methods are still required. One possibility may Ite to exploit the rapid room temperature enolization of aldehydes observed on treatment with potassium hydride in THF. ... 

Low-valent Ru(II) [150] and Rh(I) complexes catalyze aldol and Michael reactions of 2-nitrilo esters. The sequence is thought to be initiated by nitrile complexation to the transition metal. This Lewis acid-activation is followed by an oxidative addition to give a metal hydride and a nitrile complexed enolate as shown in Sch. 36. Examples including diastereoselective Ru(II) catalyzed reactions [151] and enantioselective Rh(I)-catalyzed reactions [152-154] with the large trans-chelating chiral ligand PhTRAP are shown in Tables 8 and 9. 

Examples of metal hydride and organometallic additions include reactions of lithium hydride and sodium hydride with acetaldehyde and its homologs [145-147], reactions of methyllithium and methylcopper with acrolein [148], and aldol additions of lithium enolates [125]. The geometry of the four-center, cyclic transition states for such additions seems to depend on the size of the metal atom (see Schemes 6.16 and 6.17). 

Metal cations and other Lewis acids can replace protons as reagents/catalysts for carbonyl addition reactions. Metal cations, for example, are involved in hydride and organometallic addition reactions. Metal cations and Lewis acids are also key reagents in the aldol-type reactions that are considered in Section 7.7. 

Aldol reactions. Reductive aldolization of methyl acrylate furnishes predominantly methyl jyn-2-methyl-3-hydroxyalkanoates in moderate yields. The catalyst system, consists of [(cod)RhCl]2, Me— DuPhos and Cl2Si(H)Me. For this reaction, significant interdependence of the metal, ligand, and hydride source for reactivity and selectivity has been witnessed. 

The formal conjugate addition of a hydride to a,f(-unsaturated carbonyl compounds with a subsequent aldol reaction of the in situ formed enolate has been frequently employed in organic synthesis. A broad range of procedures have been developed using various metals (e.g., rhodium, cobalt, iridium, mthenium, copper) and different reductants (typically silanes, boranes, or elemental hydrogen) [37]. 

A general mechanism of domino conjugate reduction/aldol reactions applying the in situ formation of metal hydrides 71 from metal complex 70 by reduction with... 

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