Zinc aldehyde arylation

Scheme 1.22 Kitamura and Noyori s mechanism of the asymmetric addition of dialkyl zinc to aryl aldehydes.

The reported structural chemistry of zinc aldehyde complexes is dominated by Vahrenkamp and co-workers. A systematic investigation is reported over three papers published in 1999. All X-ray structures reported in these papers are aryl aldehydes and no aliphatic aldehyde structures with zinc were found in the CSD. Zinc is frequently exploited in preparative organic chemistry and enzyme-catalyzed transformations of organic carbonyl compounds. 

The asymmetric addition of diethyl zinc to aryl aldehydes in flow has evoked much academic interest. Supported amino alcohol 6 (Scheme 4.52) was placed in a jacketed column cooled to 0 °C and pretreated with the aldehyde. A 1 1.4 aldehyde diethyl zinc solution was then flowed through the column and collected, and after a simple aqueous workup, the desired product was obtained. In one example, 5 mmol of 6 was used to produce 90 mmol of product in 90% yield and 94% ee, and in a second example 0.7 mmol of 6 produced 58 mmol of product with 92% ee [170]. 

A number of studies have also been reported using enantiopure Betti base derivatives as chiral ligands in asymmetric reactions. For example, Chan et al. reported that Betti base 33 was a useful ligand for the additional of diethyl zinc to aryl aldehydes, with excellent enantiomeric excesses... 

Pyridines are often used as catalysts or reagents particular notice has been paid recently to how pyridine coordinates to metal centers enabling a wide range of valuable reactions. Chiral pyridine-iridinium complexes, where an N-heterocyclic carbene replaces the phosphinite in Crabtree-type catalysts, have been shown to provide efficient, enantioselective hydrogenation (13AG(1)7422). Chiral-2-pyridylsulfinamides induce excellent enantiose-lecivity in the addition of diethyl zinc to aryl and alkyl aldehydes (13T8422). 

Since amines, unlike alcohols, do not react with dialkylzincs but may coordinatively bind to the zinc atom, the dilithio salt of 2,5-diisopropylpiperazine is a more potent catalyst than the piperazine itself, presumably due to the greater nucleophilic power of the dianion10. Dimethylzinc reacts rather slowly with aryl aldehydes and although the product is obtained in high enantiomeric excess, the chemical yield is low10. 

Aryl zinc reagents are considerably more reactive than alkylzinc reagents in these catalyzed additions to aldehydes.151 Within the same computational framework, phenyl transfer is found to have about a lOkcal/mol advantage over ethyl transfer.152 This is attributed to participation of the tt orbital of the phenyl ring and to the greater electronegativity of the phenyl ring, which enhances the Lewis acid character of the catalytic zinc. 

Organozinc reagents have been used in conjunction with a-bromovinylboranes in a tandem route to Z-trisubstituted allylic alcohols. After preparation of the vinylborane, reaction with diethylzinc effects migration of a boron substituent with inversion of configuration and exchange of zinc for boron.176 Addition of an aldehyde then gives the allylic alcohol. The reaction is applicable to formaldehyde alkyl and aryl aldehydes and to methyl, primary, and secondary boranes. 

The same laboratory has prepared three tridentate zinc chelates from chiral tertiary amino phenolic alcohols and used them for enantioselective addition of diethylzinc to aryl aldehydes in 70-87% ee. Results with the ligand 4 [from (1S,2S)-(+ )-pseudoephedrine] are typical. 

In a related three-component reaction procedure, aryl methyl ketones 724 have been combined with aryl aldehydes 725 and urea 726 at room temperature, using trimethylsilyl iodide as catalyst, to give 4,6-diaryl-3,4-dihydro-2(177)-pyrimidinones 727 <2005HCA2996>. A procedure using zinc iodide and microwave irradiation gave similar products <2007T1981>. 

When arylhydrazones of aldehydes or ketones are treated with a catalyst, elimination of ammonia takes place and an indole is formed, in the Fischer indole synthesis.515 Zinc chloride is the catalyst most frequently employed, but dozens of others, including other metal halides, proton and Lewis acids, and certain transition-metals have also been used. Arylhydrazones are easily prepared by the treatment of aldehydes or ketones with phenylhydrazine (6-2) or by aliphatic diazonium coupling (2-7). However, it is not necessary to isolate the arylhy-drazone. The aldehyde or ketone can be treated with a mixture of phenylhydrazine and the catalyst this is now common practice. In order to obtain an indole, the aldehyde or ketone must be of the form RCOCH2R (R = alkyl, aryl, or hydrogen). 

Arene(tricarbonyl)chromium complexes, 19 Nickel boride, 197 to trans-alkenes Chromium(II) sulfate, 84 of anhydrides to lactones Tetrachlorotris[bis(l,4-diphenyl-phosphine)butane]diruthenium, 288 of aromatic rings Palladium catalysts, 230 Raney nickel, 265 Sodium borohydride-1,3-Dicyano-benzene, 279 of aryl halides to arenes Palladium on carbon, 230 of benzyl ethers to alcohols Palladium catalysts, 230 of carboxylic acids to aldehydes Vilsmeier reagent, 341 of epoxides to alcohols Samarium(II) iodide, 270 Sodium hydride-Sodium /-amyloxide-Nickel(II) chloride, 281 Sodium hydride-Sodium /-amyloxide-Zinc chloride, 281 of esters to alcohols Sodium borohydride, 278 of imines and related compounds Arene(tricarbonyl)chromium complexes, 19... 

BINOL-derived phosphoramidites are versatile ligands in palladium-catalysed umpol-ung allylation of aryl aldehydes mediated by diethylzinc.172 The possible roles of allyl-zinc and -palladium species in the mechanism are discussed in detail. 

A mandelamide diastereomer catalyses addition of both aryl- and alkyl-zincs to heteroaromatic aldehydes in high yield and ee, giving heterocyclic propargyl alcohols, under otherwise metal-free conditions 228... 

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