2- Chloro-3-hydroxy ketones

Cleavage of a,[i-epoxy ketones.1 The reagent (1), possibly (CH3)2SC1, formed from DMSO and ClSi(CH3)3, cleaves a,(3-epoxy ketones to 2-chloro-3-hydroxy ketones with high regioselectivity (equation I). If the epoxide has a phenyl substituent, 3-chloro-2-hydroxy ketones are formed (equation II). 

Pinacolone (3,3-dimethyl-2-butanone) adds to aldehydes in an enantioselective manner when advantage of the induction by a C 2-symmetric boron enolate derived by addition of (2/ ,5/ )-l-chloro-2,5-diphenylborolane is taken. In this way, /i-hydroxy ketones, whose absolute configuration is unknown, arc obtained with 32- 84% cc58. 

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... 

The lithiation of y-chloro acetal 175 with lithium and a catalytic amount of naphthalene (4%) allowed the preparation of the intermediate 176, which can be considered as a masked lithium homoenolate, and was used for the preparation of the hydroxy ketone 179 through the hydroxy acetal 177 and dithiane 178 using known chemistry (Scheme 62)" . 

Weak Medium 300 1 15 Alcohols, phenols, and intermolecular hydroxyl to carbonyl bonding <100° 10 100-300 50 1.2- Diols, a- and most /3-hydroxy ketones o-chloro and oal-koxy phenols 1.3- Diols some /3-hydroxy ketones /3-hydroxy amino compounds /3-hydroxy nitro compounds... 

The primary product of hypohalite photolysis is a 1,5-halohydrin, the stability of which increases on passing from iodo- to bromo- to chloro-hydrins. If spontaneous elimination of hydrogen halide does not occur, the halohydrins can be converted into tetrahydrofurans by base treatment. In several instances69, 75, 88)115 it has been possible to isolate the intermediate halohydrin. Oxidation of this intermediate followed by solvolysis leads to the corresponding hydroxy ketones or in the presence of base to cyclopropyl ketones.5,57... 

C—C—O+N—C. a-Hydroxy ketones react with monosubstituted cyanamides under the influence of sodium hydroxide to yield derivatives of 2-aminooxazole (equation 125) (76S591). Oxazoles are obtained by the action of nitriles on a-diazo carbonyl compounds in the presence of Lewis acids, such as aluminum chloride or boron trifluoride, and the reaction is thought to involve the intermediacy of nitrilium salts (equation 126). Nitrilium salts are also the effective agents in the formation of oxazoles from a-chloro ketones and nitriles in the presence of tin(IV) chloride (equation 127). 

Treatment of tertiary a-hydroxy ketones with chlorosulfonyl isocyanate yields intermediates which are hydrolyzed to carbamates. The latter cyclize to 2(5//)-oxazolones on heating (equation 143). Acetone cyanohydrin is converted into the chloro derivative (292) by the... 

TL 24 2009 (1983) (0-keto ester) 25 1241 (fi-diketones to /J-hydroxy ketones), 4623 (3-oxo glutarate and adipate esters), 5083 (a-sulfenyl-/J-keto esters) (1984) 26 101 (/J-keto esters), 771 (a-PhS ketone), 4213 (/J-keto esters) (1985) 27 565 (/J-diketones to /J-hydroxy ketones), 1915 (a-keto esters) 2091 (/J-keto esters), 2657 (/J-keto esters), 3547 (2-acyl- 1,3-dithianes 2-acylthiazoles), 4737 (a-chloro ketones), 4817 (a-PhSOj ketone), 5275 (/J-keto esters and amides), 5281 (/ -keto esters), 5397 (a-chloro ketone, /J-keto ester), 5405 (/J-keto thio- and dithioesters) (1986) 28 2709 (/ -chloro-a-keto ester), 3189 (/J-keto ester) (1987) 29 4769 (3- and 4-nitro ketones), 4865 (/J-keto ester), 6167 (5-acetyl-2-isoxazolines) (1988) 30 2707 (yS-keto ester), 3701, 5705 (/J-keto ester) (1989) 31 1159 (/J-keto ester), 1615 (/J-keto ester), 1811, 3631 (/J-keto esters), 4025 (a-hydroxy ketone), 4195 (2-acyl-2-alkenoate ester), 5575 (y- and 5-keto sulfones), 7463 (/J-diketone to /f-hydroxy ketone)... 

Reaction of a p-hydroxy ketone with chloro-di-isopropylsilane provides a [3-hy-drosilyloxy ketone that delivers hydride to the ketone function in the presence of tin (IV) chloride. Hie reaction provides a highly diastereoselective method for preparing 1,3-diols via intramolecular hydrosilylation [Scheme 3.121].227... 

In addition to the foregoing 1,4-difunctional compounds used for cyclizations, the following have been used to give pyridazines or theirreduced analogs , 4-hydroxy ketones, l,4-haloketones, l,4-dibromobutane, 2,5-dibromohexane, 1,4-halo-esters, or butadiene dioxide. Hexahydropyridazine results as one of the oxidation products of 1,4-diaminobutane and its 1-butyl analog is formed in the reduction of iV-nitroso-4-chloro-dibutylamine. ... 

The key step in the asymmetric synthesis of brazilin (167a), a tetracyclic homoisoflavanoid which possesses antibacterial and antiinflammatory activities, was prepared by the enantioselective a-hydroxylation of the sodium enolate of chromanone (165) in 92% ee with chloro oxaziridine (+)-(74) <93JOCl75l>. The a-hydroxy ketone (166) was converted into (167b) in 64% overall yield from (166), by reduction of the carbonyl and acid-catalyzed cyclization (Scheme 31). 

The total synthesis of the isoprostane ( )-8-epi-PGF2a ether is accomplished via cyclization of diazo keto silyl derivative 200. Aldol condensation of diazoketone 198 with decadienal (199) in the presence of KHMDS followed by addition of LiBr provides an intermediate P-hydroxy adduct 201 which is not isolated but is immediately silylated to give silyl derivative 200.86 Diazo hydroxy ketones 201 and 203 are silylated with ClSi(Et)3 and chloro dimethyl-Mributylsilane to afford silylated diazoketones 202 and 204, respectively.86... 

One representative synthesis of prothioconazole starts [95] with the addition of the Grignard derivative of 2-chlorobenzyl chloride on the carbonyl double bond of chloromethyl 1-chloro-cyclopropyl ketone (Scheme 17.19). The untouched chlorine atom of the chloromethyl group is then classically substituted with 1,2,4-triazole. From this intermediate, one way to obtain the 2,4-dihydro-3H-l,2,4-triazole-3-thione of prothioconazole is by direct lithiation of the 1,2,4-triazole at position 5 with n-butyl lithium and reaction with sulfur. The commercially available compound is a mixture of two enantiomers (chirality of the quaternary carbon bearing the hydroxy group). 

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