Zinc complexes alcohols

Ito and co-workers observed the formation of zinc bound alkyl carbonates on reaction of carbon dioxide with tetraaza macrocycle zinc complexes in alcohol solvents.456 This reversible reaction was studied by NMR and IR, and proceeds by initial attack of a metal-bound alkoxide species. The metal-bound alkyl carbonate species can be converted into dialkyl carbonate. Spectroscopic studies suggested that some complexes showed monodentate alkyl carbonates, and varying the macrocycle gave a bidentate or bridging carbonate. Darensbourg isolated arylcarbonate compounds from zinc alkoxides as a by-product from work on polycarbonate formation catalysis.343... 

Kimura and co-workers have synthesized a series of alkoxide complexes with the alcohol functionality as a pendent arm.447 674 737 A zinc complex of l-(4-bromophenacyl)-l, 4,7,10-tetraaza-cyclododecane was also synthesized by the same workers to mimic the active site of class II aldolases. The X-ray structure shows a six-coordinate zinc center with five donors from the ligand and a water molecule bound. The ketone is bound with a Zn—O distance of 2.159(3) A (Figure 12). Potentiometric titration indicated formation of a mixture of the hydroxide and the enolate. Enolate formation was also independently carried out by reaction with sodium methoxide, allowing full characterization.738... 

Thiolate ligated zinc complexes have been characterized with a co-crystallized methanol molecule that is hydrogen bonded to a zinc-bound sulfur, and the possibility the alcohols may be activated without coordination to the metal center was discussed by Shoner et al.904... 

Jensen et al. reported the stereoselective polymerization of D,L-lactide with dibenzyloxidezinc(2,4,6-trimetylphe-nyimidazol-2-ylidene), which was synthesized as shown in Scheme 39.100 Surprisingly, a mixture of the heterocarbene and benzyl alcohol was a better catalyst for polylactide formation than the zinc complex, and unlike 50 the mixture produced heterotactically enriched polylactide. 

Other examples involved the use of chiral Schiff base-zinc complexes as catalysts [33 a] and polymer-supported chiral N-tritylaziridino alcohols as catalysts. The stereoselectivity was reported to be up to 97% ee for aUphatic and up to 96% ee for aromatic aldehydes [103]. 

The NAD+-dependent alcohol dehydrogenase from horse liver contains one catalytically essential zinc ion at each of its two active sites. An essential feature of the enzymic catalysis appears to involve direct coordination of the enzyme-bound zinc by the carbonyl and hydroxyl groups of the aldehyde and alcohol substrates. Polarization of the carbonyl group by the metal ion should assist nucleophilic attack by hydride ion. A number of studies have confirmed this view. Zinc(II) catalyzes the reduction of l,10-phenanthroline-2-carbaldehyde by lV-propyl-l,4-dihy-dronicotinamide in acetonitrile,526 and provides an interesting model reaction for alcohol dehydrogenase (Scheme 45). The model reaction proceeds by direct hydrogen transfer and is absolutely dependent on the presence of zinc(II). The zinc(II) ion also catalyzes the reduction of 2- and 4-pyridinecarbaldehyde by Et4N BH4-.526 The zinc complex of the 2-aldehyde is reduced at least 7 x 105 times faster than the free aldehyde, whereas the zinc complex of the 4-aldehyde is reduced only 102 times faster than the free aldehyde. A direct interaction of zinc(II) with the carbonyl function is clearly required for marked catalytic effects to be observed. 

At least four protonation-deprotonation equilibria have been implicated in catalysis, having p a values 6.4, 7.6, 9.2 and 11.2.562,563 The pKa of 9.2 has been attributed to the deprotonation of the zinc-bound water, and the values of 7.6 and 11.2 to its deprotonation in the binary complexes with NAD+ and NAD(H) respectively.563-565 The pJ a value of 6.4 has been assigned to the deprotonation of the zinc-coordinated alcohol.566 The electronic spectra of Co(c)2Zn(n)2-LADH and its binary complex with NAD+ are pH dependent, with pKa values of around 8 and 9 respectively.567 These have been related to the pKa values of 7.6 and 9.2 reported for the Zn4 enzyme described above. The electronic spectrum of the binary complex of Co(c)2Zn(n)2-LADH with NADH is independent of pH in the range 6 to 9. 

A C2-symmetric bisoxazolidine-zinc complex catalyses alkynylation of aldehydes, giving propargyl alcohols in high yield and ee.190... 

In 1992 Kobayashi et al. [47] reported the first catalytic and enantioselective cyclo-propanation using the Furukawa modification [48] of the Simmons-Smith reaction of allylic alcohols in the presence of a chiral bis(sulfonamide)-Zn complex, prepared in-situ from the bis(sulfonamide) 63 and diethylzinc. When cinnamyl alcohol 62 was treated with EtgZn (2 equiv.), CHgIg (3 equiv.), and the bis(sulfonamide) 63 (12 mol %) in dichloromethane at -23 °C, the corresponding cyclopropane 64 was obtained in 82 % yield with 76 % ee (Sch. 26). They proposed a transition state XXIII (Fig. 5) in which the chiral zinc complex interacts with the oxygen atom of the allylic alkoxide and the iodine atom of iodomethylzinc moiety. They also reported the use of the bis(sulfonamide)-alkylaluminum complex 65 as the Lewis acidic component catalyzing the Simmons-Smith reaction [49]. 

The scope of the reaction was examined with a catalyst prepared from the benzene sulfonamide and DIBAL, because it was found that essentially the same induction could be obtained as with those obtained from tri-/so-butyl aluminum. Two years earlier the authors had reported that this Simmons-Smith reaction could also be catalyzed by the aluminum-free sulfonamide 132 (optimum with Ar = /7-NO2C6H4) the induction obtained is listed in the far right column of Table 8 [34]. It was proposed that a zinc complex of 132 is generated in-situ. Surprisingly, with the exception of the silyl-substituted allyl alcohol (the last entry in the table) [35], almost identical asymmetric induction obtained by use of the aluminum-containing and aluminum-free catalysts. The main advantage of the diazaaluminolidine catalyst is that it is apparently more soluble than the aluminum-free bis-sulfonamide catalyst, with the result that a tenfold increase in concentration (0.1 m) can be used this might explain the increased rate observed for the diazaaluminolidine catalyst. Finally, it has recently been reported that a catalyst formed from the Ci symmetrical sulfonamide 135 and DIBAL will induce the formation of 131 from cinnamyl alcohol in 68 % ee [36]. 

The slow nucleophilic addition of dialkylzinc reagents to aldehydes can be accelerated by chiral amino alcohols, producing secondary alcohols of high enantiomeric purity. The catalysis and stereochemistry can be interpreted satisfactorily in terms of a six-membered cyclic transition state assembly [46,47], In the absence of amino alcohol, dialkylzincs and benzaldehyde have weak donor-acceptor-type interactions. When amino alcohol and dialkylzinc are mixed, the zinc atom acts as a Lewis acid and activates the carbonyl of the aldehyde. Zinc in this amino alcohol-zinc complex is regarded as a kind of chirally modified Lewis acid. Various kinds of polymer-supported chiral amino alcohol have recently been prepared and used as ligands in dialkylzinc alkylation of aldehydes. 

Zinc complexes, consisting of amine, amino alcohol, alcohol, sulfide, or phosphine as ligand, catalyzed 1,4-addition of Grignard reagents to a,) -unsaturated carbonyl compounds [447,448]. An optically active ligand on zinc achieved asymmetric 1,4-addition, the best result is presented in Eq. (204) [448]. 

Fig. 16 The mechanism implicated by kinetic data by which a dinuclear zinc complex catalyzes the cyclization of RNA analogs. The pKa of the Zn-coordinated water was found to be 8.0 once deprotonated, the resulting coordinated hydroxide acts as a base to deprotonate the secondary alcohol, which acts as the nucleophile in a subsequent step.

The fact that cinnamyl methyl ether underwent cyclopropanation under similar conditions to afford the corresponding cyclopropane as an almost racemic mixture indicates that the free hydroxy group is necessary for producing an effective chiral environment. This can presumably take place through complexation as a zinc alkoxide. The authors propose that a trinuclear zinc complex 89, in which both the oxygen atom of a zinc alkoxide and iodine atom of iodo-methylzinc contribute to the Lewis character, must be close to the transition structure of the reaction. This might account also for the distinct enantioselectivity between the allylic alcohol and its methyl ether. 

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