Benzoin reactions catalysis

Shortly after publishing the racemic cross silyl benzoin reaction, Johnson and co-workers reported an enantioselective variant ntilizing metallophosphite catalysis [48]. The lithiophosphite adds to the acyl silane and proceeds throngh the remain-... 

The triazol-5-ylidene 12 was found to be a powerful catalyst for the conversion of formaldehyde to glycolaldehyde in a formoin reaction [25.] The concept of triazolium salt catalysis appeared to show promise, and consequently our research group undertook the synthesis of a variety of chiral triazolium salts for the asymmetric benzoin reaction [26]. However, the ce-values and catalytic activities shifted widely with slight structural changes in the substitution pattern of the triazolium system. The most active catalyst 15 (Fig. 9.4) afforded benzoin (6, Ar = Ph) in its (R -configuration with 75% ee and a satisfactory yield of 66%. 

Enders D, Muller-Huwen A (2004) Asymmetric synthesis of 2-amino-1,3-diols and D-erythro-sphinganine. Eur J Org Chem 2004 1732 Enders D, Niemeier O (2004) Thiazol-2-ylidene catalysis in intramolecular crossed aldehyde-ketone benzoin reactions. Synlett 2004 2111-2114... 

Enders D, Niemeier O, Balensiefer T (2006c) Asymmetric intramolecular cros-sed-benzoin reactions by N-heterocyclic carbene catalysis. Angew Chem Int Ed Engl 45 1463... 

Benzoin condensation/ sometimes known as the benzoin reaction/ is the condensation between aromatic aldehydes to form a-hydroxyl ketones (i.e., benzoins) in the presence of a catalyst. It should be pointed out that benzoin itself is not produced from benzaldehyde by acid or base catalysis or under thermal or free-radical conditions in fact, benzoin is generated from benzaldehye in the presence of a catalyst. The first benzoin condensation catalyzed by cyanide ion was reported by Stange in 1824, and has been extensively stud-... 

Scheme 2.17 Breslow s postulate of NHC catalysis in benzoin reactions.

A review of the asymmetric Stetter and asymmetric benzoin reactions focuses mainly on two classes of highly successful catalysts NHCs and metallophosphites. A new NHC, pyrido[l,2-a]-2-ethyl[l,2,4]triazol-3-ylidene (99), is a powerful catalyst of benzoin condensation in the presence of potassium f-butoxide. A DFT study of the mechanism suggests that the f-butanol solvent is explicitly involved. o-Phthalaldehyde chalcones (100) undergo intramolecular aldehyde-ketone crossed-benzoin condensation to naphthalenone tertiary alcohols (101) in yields up to 94%, in 20 min, using NHC catalysis. ... 

NHC catalysis has been efficiently employed in an intramolecular crossed-benzoin reaction of symmetrical reactants. This desymmetrization strategy can be applied to (g) asymmetric synthesis with chiral NHCs. As an example, bis(acyloin) (91) containing three contiguous quaternary bridgehead chiral centres was synthesized and structurally characterized by X-ray crystallography. 

NHC catalysis of Stetter and benzoin reactions by triazolidenes has been investigated via in situ observation of intermediate 3-(hydroxybenzyl)azolium salts of the benzaldehyde substrates. Equilibrium constants for their formation are reported, together with rate constants for hydrogen-deuterium exchange at the a-carbon. 

In 2012, Melchiorre et al. reported a novel stereoselective access to chiral frans-fused tetracyclic indole-based products having four stereogenic centres on the basis of a multicatalytic tandem Diels-Alder-benzoin reaction involving JV-Boc protected 3-(2-methyl-indol-3-yl)acrylaldehyde derivative and fra s-l,2-dibenzoylethylene derivative as substrates." As shown in Scheme 2.32, the process was successively induced by chiral diphenylproli-nol trimethylsilyl ether in the presence of bullgr 2,4,6-trimethylbenzoic acid (TMBA) as co-catalyst for the Diels-Alder reaction (trienamine catalysis), and an AT-heterocyclic carbene for the following cross-benzoin condensation... 

In 1966, Sheehan reported a remarkable asymmetric benzoin reaction catalyzed by chiral thiazolium salts with moderate levels of enantioselectivity [56-59]. In 2002, Enders and coworkers made an important breakthrough when they reported the first highly enantioselective intermolecular benzoin reaction catalyzed by a triazolium salt derived from ferf-leucine [Eq. (1)] [60]. Since then, catalyst development for NHC catalysis has seen exponential growth for new triazolium salts derived from chiral amino acids and amino alcohols. 

In 2006, Enders reported an intramolecular cross benzoin reaction of bifunctional substrates 53 containing aldehyde and ketone groups to give various six-membered cyclic acyloins 54 in moderate to good yields. Up to 98% ee has been obtained upon catalysis by the tetracyclic triazolium salt 52 (Scheme 36.15) [21aj. Suzuki also developed a similar intramolecular asymmetric cross benzoin reaction [2lb]. 

Although the catalysis of the dimerization of aldehydes to acyloins by thiazolium ion has been known for some tlrae, the development of procedures using anhydrous solvents which give satisfactory yields of acyloins on a preparative scale was first realized in the submitters laboratories. The mechanism proposed by Breslow - for the thiazolium ion-catalyzed reactions is similar to the Lapworth mechanism for the benzoin condensation with a thiazolium ylide replacing the cyanide ion. Similar mechanisms are involved... 

Nucleophilic addition to C=0 (contd.) ammonia derivs., 219 base catalysis, 204, 207, 212, 216, 226 benzoin condensation, 231 bisulphite anion, 207, 213 Cannizzaro reaction, 216 carbanions, 221-234 Claisen ester condensation, 229 Claisen-Schmidt reaction, 226 conjugate, 200, 213 cyanide ion, 212 Dieckmann reaction, 230 electronic effects in, 205, 208, 226 electrons, 217 Grignard reagents, 221, 235 halide ion, 214 hydration, 207 hydride ion, 214 hydrogen bonding in, 204, 209 in carboxylic derivs., 236-244 intermediates in, 50, 219 intramolecular, 217, 232 irreversible, 215, 222 Knoevenagel reaction, 228 Lewis acids in, 204, 222 Meerwein-Ponndorf reaction, 215 MejSiCN, 213 nitroalkanes, 226 Perkin reaction, 227 pH and, 204, 208, 219 protection, 211... 

From mechanistic considerations and assuming that cleavage and formation of (R)-benzoin are in equilibrium, BAL should also catalyze carboligation. Consequently, BAL-catalyzed acyloin condensation of benzaldehyde in an aqueous buffer/DMSO mixture resulted in almost quantitative formation of enantiomeri-cally pure (R)-benzoin [Scheme 2.2.7.21, Eq. (1)]. The reaction was carried out on a preparative scale with different aromatic and heteroaromatic aldehydes [62]. From the viewpoint of the organic-preparative chemist, it is important to mention that crude cell extracts of the recombinant E. coli strain overexpressing the BAL gene are sufficient for catalysis, hence, purification of the enzyme is not necessary. 

Georg Bredig (1868-1944)137 138 was essentially a physical chemist, who worked in catalysis, reaction kinetics, and electrochemistry. For physical organic chemistry his studies of the catalysed decomposition of diazoacetic ester, of reactions in concentrated sulphuric acid, and of the catalysis of the benzoin condensation by cyanide ion are of interest. The last-mentioned work was done in 1904, when Bredig confirmed,... 

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