A-Hydroxy acetone

In 1989, Sakurai et al. reported that allyltrifluorosilanes react with a variety of a-hydroxy ketones in the presence of stoichiometric amount of triethylamine to yield the corresponding tertiary homoallylic alcohols in an extremely high regio-and diastereoselective manner10 (Scheme 3.2h). Upon reacting with a-hydroxy acetone, the (L )-crotylsilane 4E gave 6-syn as a major product in 83% yield with... 

Bis(alkylsulfanyl)cyclopropanes (cyclopropanone dithioacetals) are transformed to a-hydroxy-acetones in hot aqueous formic acid and to acetones in aqueous trifluoroacetic acid at ambient temperature, the latter reaction probably via reduction of an intermediate ot-methyl thioketone by methylsulfide. For example, 7 gave 8 with hot aqueous formic acid and 9 with trifluoroacetic acid. ... 

The hydrogenation of a-hydroxy ketones can also be conducted with high enantioselec-tivities. In one commercial process shown in Equation 15.67, optically active 1,2-propane diol is prepared in 94% ee by the hydrogenation of a-hydroxy acetone in the presence of a ruthenium catalyst ligated by Tol-BINAP. This process is reported to be conducted on the scale of 50 tons per year for the synthesis of (S)-oxafloxazin, a bactericide that is now being sold in enantioenriched form. - ... 

Acetone cyanhydrin (a-Hydroxy sobutyronitrile) By this method, the nitrile of an a-hydroxy acid U necessarily obtained. 

The outstanding chemical property of cyanohydrins is the ready conversion to a-hydroxy acids and derivatives, especially a-amino and a,P-unsaturated acids. Because cyanohydrins are primarily used as chemical intermediates, data on production and prices are not usually pubUshed. The industrial significance of cyanohydrins is waning as more direct and efficient routes to the desired products are developed. Acetone cyanohydrin is the world s most prominent industrial cyanohydrin because it offers the main route to methyl methacrylate manufacture. 

Cyanohydrin Synthesis. Another synthetically useful enzyme that catalyzes carbon—carbon bond formation is oxynitnlase (EC 4.1.2.10). This enzyme catalyzes the addition of cyanides to various aldehydes that may come either in the form of hydrogen cyanide or acetone cyanohydrin (152—158) (Fig. 7). The reaction constitutes a convenient route for the preparation of a-hydroxy acids and P-amino alcohols. Acetone cyanohydrin [75-86-5] can also be used as the cyanide carrier, and is considered to be superior since it does not involve hazardous gaseous HCN and also virtually eliminates the spontaneous nonenzymatic reaction. (R)-oxynitrilase accepts aromatic (97a,b), straight- (97c,e), and branched-chain aUphatic aldehydes, converting them to (R)-cyanohydrins in very good yields and high enantiomeric purity (Table 10). 

Developed as a carboxyl protective group for peptide synthesis because of its stability to hydrogenolysis and acidic conditions, the acetol (hydroxy acetone) ester is prepared by DCC coupling (68-92% yield) of the acid with acetol. It is cleaved with TBAF in THF. ... 

A solution of 1.0 g of A -3,11-diketo-20-cyano-21-acetoxy-pregnene in 10 cc of benzene is treated with 1.0 g of osmium tetroxide and 0.43 g of pyridine. After standing at room temperature for 18 hours, the resulting solution is treated successively with 50 cc of alcohol, and with 50 cc of water containing 2.5 g of sodium sulfite. The mixture is stirred for 30 hours, filtered, and the filtrate acidified with 0.5 cc of acetic acid and concentrated to small volume in vacuo. The aqueous suspension is then extracted four times with chloroform, the chloroform extracts are combined, washed with water and concentrated to dryness in vacuo. Recrystallization of the residue from acetone gives 3,11,20-triketo-17(a)-21-dihydroxy-pregnane MP 227° to 229°C. This compound is then treated with acetic anhydride and pyridine for 15 minutes at room temperature to produce 3,11,20-triketo-17(a)-hydroxy-21-acetoxy-pregnane or cortisone acetate. 

Alkenes have also been converted to more highly oxidized products. Examples are (1) Treatment with KMn04 in aqueous acetone containing acetic acid gives a-hydroxy ketones. (2) 1,2-Disubstituted and trisubstituted alkenes give a-chloro ketones when oxidized with chromyl chloride in acetone RCH=CR R"—> RCOCCIR R". (3) a-Iodo ketones can be prepared by treating alkenes with... 

In analogy with a-hydroxy-substituted alkoxyallene adducts, the corresponding allenylamines, e.g. 109 in Scheme 8.30 and 85 in Eq. 8.20, can be cyclized to dihydropyrrole derivatives either under basic conditions [43, 74, 75] or by treatment with catalytic amounts of AgN03 in acetone or acetonitrile [43, 73, 74],... 

Figure 2. Free energy profile for converting di hydroxy acetone phosphate, the substrate (abbreviated S) and glyceraldehyde 3-phosphate, the product (abbreviated P), with intermediate formation of the enedi-olate (abbreviated Z). Catalysis occurs either by a free carboxyl group (levels connected by dotted lines) or by triose-phosphate isomerase (levels connected by dashed lines). The vertical arrows show the limits of those states that are less well defined as a result of uncertainty in the experimental data. The transition state marked "e" refers to the exchange of protons between the solvent and the enzyme-bound enediol intermediate (EZ). Reproduced with permission of the authors and the American Chemical Society.

Z)-Trisubstituted aRylic alcohols. The conditions used by Bestmann et al. (7, 329) for preparation of (Z)-disubstitutcd alkcncs via the Wittig reaction also can provide a stereoselective route to (Z)-trisubstiluted allylic alcohols. An example is the reaction of ethylidenetriphenylphosphorane with the THP ether of hydroxy-acetone (equation 1). The stereoselectivity is decreased with other protecting... 

Important extensions of proline catalysis in direct aldol reactions were also reported. Pioneering work by List and co-workers demonstrated that hydroxy-acetone (24) effectively serves as a donor substrate to afford anfi-l,2-diol 25 with excellent enantioselectivity (Scheme 11) [24]. The method represents the first catalytic asymmetric synthesis of anf/-l,2-diols and complements the asymmetric dihydroxylation developed by Sharpless and other researchers (described in Chap. 20). Barbas utilized proline to catalyze asymmetric self-aldoli-zation of acetaldehyde [25]. Jorgensen reported the cross aldol reaction of aldehydes and activated ketones like diethyl ketomalonate, in which the aldehyde... 

Epoxydioxepane 124 was converted with a LiCN-acetone complex (prepared from acetone cyanohydrine and methyllithium CAUTION ) into /3-hydroxy nitrile 127 <2004TL7201>, and epoxydioxepane 128 with lithium amide into hydroxydioxepin 128 (Scheme 32) <2004RJOC1830>. 

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