Ketones, 2-chloro

Bromo ketones are commonly employed and are much easier to dehydro-halogenate than chloro ketones, although the latter are not so susceptible to reduction and rearrangement. lodo ketones are generally less accessible and very prone to reduction. 

Presumably, jS-chloro ketones could also react similarly with methyl(ene) ketones. Another logical extension is the possibility of synthesizing pyrylium salts by dehydrogenative condensation of -chlorovinyl ketones with oleflns like styrene, in the presence of stannic chloride (the olefins so far tested, like isobutene, are not suitable structurally). 

The hydrogen chloride thus produced can in turn react with the diazoketone to yield a a-chloro ketone. In order to avoid this side reaction, two equivalents of diazomethane are used. The second equivalent reacts with HCl to give methyl chloride. ... 

With a-chloro ketones, lithiated (2S)-2,5-dihydro-2-isopropyl-3,6-dimethoxypyrazincs react at the carbonyl group to give the aldol adducts which, upon subsequent treatment with sodium hydroxide, give the epoxides 413. Hydrolysis leads to fi.y-epoxy amino acids, or further functionalized amino acids when the epoxide is opened with nucleophiles13. 

Thiazolines (2,3-dihydrothiazoles) were also prepared under microwave irradiation. Hamelin and coworkers have described the alumina-supported solvent-free synthesis of various 4-iminothiazolines by condensation of disymmetric thioureas and a-chloro ketone (Scheme 10). The experiments... 

In the case of silyl enol ethers the inner bond can be cleaved with FeCl3, giving a ring-enlarged (J-chloro ketone Ito, Y Fujii, S. Saegusa, T. J. Org. Chem., 1976,41,2073 Org. Synth. VI, 327. 

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 net structural change is the same for both mechanisms. The energy requirements of the cyclopropanone and semibenzilic mechanism may be fairly closely balanced.87 Cases of operation of the semibenzilic mechanism have been reported even for compounds having a hydrogen available for enolization.88 Among the evidence that the cyclopropanone mechanism operates is the demonstration that a symmetrical intermediate is involved. The isomeric chloro ketones 12 and 13, for example, lead to the same ester. 

The thermo- and photocycloaddition of alkenes will be discussed in Chapter 12, on pericyclic reactions. On the other hand, transition-metals have effectively catalyzed some synthetically useful cycloaddition reactions in water. For example, Lubineau and co-worker reported a [4 + 3] cycloaddition by reacting a,a-dibromo ketones with furan or cyclopen-tadiene mediated by iron or copper, or a-chloro ketones in the presence of triethylamine (Eq. 3.48).185... 

Parallel array synthesis was used to access the 3-aryl-tetrahydro-l,2-diazepines 90 (and other related compounds) by cyclisation of the chloro ketones 88 on reaction with hydrazine to give 89 followed by sulfonamide formation the Si-TrisAmine was added at the end as a scavenger to remove any unreacted arylsulfonyl chloride remaining <06MCL3777>. 

The cyclic a-chloro ketone 81 which forms the (Z)-enolate only also underwent the asymmetric Darzens condensation with various aldehydes by use of the Merck catalyst 7 (R=4-CF3, X=Br) under analogous conditions to furnish the a,(3-epoxy ketones 82 with up to 86 % ee,160611 as shown in Scheme 25. It should be noted that this high enantioselectivity was attained by the reaction at room temperature. 

S. Arai, Y. Shirai, T. Ishida, T. Shioiri, Phase-Transfer Catalyzed Asymmetric Darzens Reactions of Cyclic a-Chloro Ketones , J. Chem. Soc., Chem. Commun. 1999, 49-50. 

M. Prorok, A. Albeck, B. M. Foxman, R. H. Abeles, Chlo-roketone Hydrolysis by Chymotrypsin and N-Methylhistidyl-57-chymotrypsin Implications for the Mechanism of Chymotrypsin Inadivation by Chloro-ketones , Biochemistry. 1994,33, 9784-9790. 

Many synthetic routes have been developed to access the saturated oxazolo[3,2- ]pyridine ring system. Among those, the most efficient ones rely on a similar strategy starting from an amino alcohol 360 and a bis-electrophile 361, the latter being either a bis-aldehyde, a keto-ester, a chloro-ketone, or a chloroalkyne (Scheme 96). Among these electrophiles, the first two have demonstrated their utility and generality over the years and have been used for the preparation of many saturated oxazolo[3,2- ]pyridines 362. 

Sprio et al. reported the preparation of 6-acetylimidazo[2,l-Z)]thiazoles derivatives 57 (74JHC91). TTie synthesis involves substituted 4-(2-thiazo-lyl)aminoisoxazoles 56, which were obtained in good yield by the reaction of N-(3,5-dimethylisoxazol-4-yl) thiourea 55 with a-chloro ketones. Subsequent isoxazole ring opening led to intermediates which readily underwent cyclization by refluxing in acetic acid or ethanol/hydrochloric acid. 

An example of a whole-cell process is the two-step synthesis of an enantiopure epoxide by asymmetric reduction of an a-chloro ketone (Scheme 6.4), catalyzed by recombinant whole cells of an Escherichia coli sp. overexpressing an (R)-KRED from Lactobacillus kefir and GDH from Thermoplasma acidophilum, to the corresponding chlorohydrin, followed by non-enzymatic base-catalyzed ring closure to the epoxide [17]. 

The following data are closely related to the results of a Russian team, who synthesized lactone- and lactam-bridged photochromes and studied their transformations. 2,5-Dimethyl-3-thienylacetic acid with a-chloro ketone in base gives ester 206, which undergoes cyclization when heated with K2CO3 in DMF under an inert atmosphere to give lactone 207 in 70-75% yields (Scheme 61). The reaction can be performed in situ without isolation of the ester (06ZOR1827)... 

Symmetrical and unsymmetrical thenoines 214-217 were synthesized analogously (02MI1). Thenoine 213 is easily transformed into 1,2-dione 218 and chloro ketone 219 (01IZV113). Ethane-1,2-dione derivatives 220 can be prepared by a one-pot reaction of 3-methylbenzothiophene with oxalyl chloride and AICI3 (02MI1) (Scheme 63). 

Symmetrical and unsymmetrical thenoines, diketones, and chloro ketones 213-225 containing substituted thienyl, benzothiophene, and other moieties are versatile precursors of structures containing various heterocycles as bridges. Chloro ketones were used, for example, in the synthesis of photochromic thiazoles 226 (01IZV113) and tetrathiafulva-lenes 227 (99CL1071) (Scheme 65). 

There is a net reduction of a-chlorosulfenyl-oc-chloro ketones under hydrolytic conditions [267]. The sulfur atom undergoes a series of contrapolarizing changes (a-d-a). The carbonyl group also plays a crucial accentuation role in the various steps of the reaction. 

Since cyclobutanones are often produced by dichloroketene addition to an alkene (see Section 1.3.5.1.), a,a-dichlorocyclobutanones are very common intermediates. These can be reduced to the monochlorocyclobutanones (see Section 5.2.1.1.). It was reported249 that the C —Cl dipole has a pronounced effect on the sodium borohydride reduction of these compounds. For example, in the reduction of e ra-7-chloro-7-methylbicyclo[3.2.0]hept-2-en-6-one, the normal preference for an exo-face attack was reversed and the exo-alcohol was the major product exo-7-chlorobicyclo[3.2.0]hept-2-en-exo-6-ol exo-2d and exo-7-chlorobicy-clo[3.2.0]hept-2-en-en /o-6-ol endo-2A were obtained in a 78 22 ratio. On the other hand, when the corresponding endo-chloro ketones were reduced, the C —Cl dipole resulted in exclusive formation of the endo-alcohols endo-2b, c. 

A flask should be used that is constructed 1n such a manner that the chloro ketone solution drips directly from the addition funnel into the reaction mixture. Any portion that flows along the sides of the flask will freeze. 

The diazonium salt 35 (Scheme 13) couples with the chloro ketones 36 to yield the pyrazoles 37 via a Japp-Klingemann type reaction followed by ring... 

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