Dicarbonyl compound, reductive coupling

The reductive coupling of the dicarbonyl compound 6 induced by a low-valent titanium species gives initially the dihydroporphycenes 7 which then spontaneously aromatize in the presence of oxygen to yield the porphycenes 8. 

The coupling reaction of arenediazonium ions with semidione radicals (12.84, obtainable by reduction of 1,2-diketones, 12.83) is also included here in the discussion of 1,3-dicarbonyl compounds, although it is a coupling with a nucleophilic radical and does not strictly belong in this context. The reaction (Scheme 12-43) was... 

Reductive Cyclizations of Dicarbonyl Compounds (Pinacol and McMurry Couplings) 529... 

The cationic iridium complex [Ir(cod)(PPh3)2]OTf, when activated by H2, catalyzes the aldol reaction of aldehydes 141 or acetal with silyl enol ethers 142 to afford 143 (Equation 10.37) [63]. The same Ir complex catalyzes the coupling of a, 5-enones with silyl enol ethers to give 1,5-dicarbonyl compounds [64]. Furthermore, the alkylation of propargylic esters 144 with silyl enol ethers 145 catalyzed by [Ir(cod)[P(OPh)3]2]OTf gives alkylated products 146 in high yields (Equation 10.38) [65]. An iridium-catalyzed enantioselective reductive aldol reaction has also been reported [66]. 

Reduction of dicarbonyl compounds can be expected to lead to a cyclic 1,2-glycol formed by the intramolecular coupling of radical intermediates. 

Numerous applications of this chemistry to the synthesis of leukotrienes have been reported, as illustrated for the preparation of 12-hydroxyeicosatetraenoic acid (189 Scheme 41).154 Reaction of the carbe-noid precursor (190) with furan in the presence of rhodium(II) acetate generated a furanocyclopropane, which on standing reverted to predominantly the (Z, )-isomer (191). Reduction of the dicarbonyl compound (191) gave the diol (192), which was then selectively converted to the bromide (193). Subsequently, (193) was coupled with the alkynide (194), followed by Lindlar reduction and deprotection to produce (189). The overall procedure is quite general and has been applied to a range of related compounds (195-199)135-138 and useful synthetic fragments (200 and 201).153... 

Fig. 17.55. Reductive coupling of a dicarbonyl compound to afford diastereomeric glycols or diastereomeric alkenes (McMurry reaction).

The reductive coupling of carbonyl compounds with formation of C-C double bonds was developed in the early seventies and is now known as McMurry reaction [38, 39]. The active metal in these reactions is titanium in a low-valent oxidation state. The reactive Ti species is usually generated from Ti(IV) or Ti(III) substrates by reduction with Zn, a Zn-Cu couple, or lithium aluminum hydride. A broad variety of dicarbonyl compounds can be cyclized by means of this reaction, unfunctionalized cycloalkenes can be synthesized from diketones, enolethers from ketone-ester substrates, enamines from ketone-amide substrates [40-42], Cycloalkanones can be synthesized from external keto esters (X = OR ) by subsequent hydrolysis of the primary formed enol ethers (Scheme 9). 

Exploration of the reduction of dicarbonyl compounds has centered on attempts to achieve intramolecular coupling of radical intermediates to give a cyclic 1,2-diol. A mechanistic study of the production of cyclopropanediols, during the reduction of 1,3-dibenzoylpropane in acetonitrile, has been made [110]. It is suggested that the ratedetermining cyclization step is the addition of the radical anion from one ketone function onto the second carbonyl group in the same molecule. 

Intramolecular free radical cyclization of dicarboxylic esters leads to a-hydroxy ketones (acyloins). Reductive coupling of dicarbonyl compounds provides 1,2-diols ipinacols) and further reaction of these yields cycloalkenes (McMurry reaction). These cyclization reactions are especially valuable for the preparation of medium and large rings that are not readily accessible by other methods. 

The corresponding AGV -dimethyl compound [DMPEDA, (/ ,/ )-27] was similarly obtained by reductive coupling, together with the me.yocompound2l,2 purified by flash chromatography, and resolved with tartaric acid22. It has been used for the formation of chiral enamines with aldehydes (Section D.l.5.2.1.) or dicarbonyl compounds and for enantioselective Grignard addition (Section D.l.3.1.4.). 

Cycloalkenes. McMurry and Kees have described an intramolecular coupling of dicarbonyl compounds to cycloalkenes. In the intermolecular version of this reaction titanium(O) powder obtained by reduction with potassium or lithium is used (7, 368). In the intramolecular reaction a superior coupling reagent is prepared by reduction of TiClg with a zinc/copper couple in DME. 

Powerful methods make use of metal-catalyzed macrocyclization. We mention the following the ally lie alkylations catalyzed by palladium (Fig. 12a) the reductive coupling of dicarbonyl compounds (Fig. 12b) the... 

The asymmetric reduction of y-phenylseleno ketones and the intramolecular substitution of the phenylselenone residue by the oxygen atom of a hydroxy group led to 2-substituted tetrahydrofurans (13OL3906). Polysubstituted furans were formed in the photoredox neutral coupling of alkynes with 2-bromo-1,3-dicarbonyl compounds. The reaction was carried out without any external stoichiometric oxidants (130L4884). 

If this explanation is correct one can suggest that the above mentioned reactions could run separately. In proving this assumption we have suceeeded unprecedentedly to carry out reductive coupling polymerization of the conjugated dicarbonyl compound benzil under the influence of the Friedel-Crafis metathesis catalytic system WCU + AlCls. In this case the quantity of the transition metal compound is less than the quantity of the Ti reagent used for... 

In recent years, synthesis of pyrroles has drawn the attention of chemists. Traditional methods used for pyrrole synthesis include the Hantzsch reaction [45] and the Paal-Knorr condensation reaction [46,47], The latter is the most widely used method, which involves the cyclocondensation reaction of 1,4-dicarbonyl compounds with primary amines to produce substituted pyrroles. In addition, there are several methods such as 1,3-dipolar cydoaddition reaction, aza-Wittig reaction, reductive coupling, and titanium-catalyzed hydroamination of diynes. Scheme 1 shows several catalysts used in this type of reaction [44]. 

In the original formulation [81a], DBN and a slight molar excess of AgN03 in MeCN solution were used. Depletion of the starting penicillanic ester was followed by tic and, when complete, obtained silver azetidinyl mercaptides 126 were in situ treated with acyl chlorides to afford thioesters 127 these in turn were oxidized at the butenoate double bond to give lH-4-thioesters 128, key intermediates of Woodward s original phosphorane-thioester cyclization route to penems [1, 48], or ozonized to the iV-oxalo compounds 129, immediate penem precursors by a newly discovered reductive dicarbonyl coupling [82]. 

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