Ketones condensation with sulfones

A variety of ketones and aldehydes have been condensed with sulfones, using r-BuOK catalysis in N,N-dimclhylacclamidc solvent.352 Typical results - for a-meth-ylcarbonyl compounds - include useful yields of the corresponding butadiene, whereas aromatic ketones give variations on the theme. a-Tetralone, for example, gives naphthalene and its a-methyl derivative (mainly the latter), but acetophenone interestingly gives some p-terphenyl. 

Fentanyl and its analogs are made from TV-substituted-4-piperidones [i.e., from the same intermediates of the reversed esters of pethidine (p. 266)]. These ketones condense with aniline under the influence of catalysts such as toluene-p-sulfonic acid(2) and zinc chloride(18) to give Schiff bases, which are reduced to diamines 4 by NaBH4 or LAH. Recently, the direct conversion of 4-piperidones to 4-anilino derivatives 4 has been achieved by reductive amination with aniline and sodium cyanoborohydride (NaBH3CN).(19) The diamines are acylated with propionic anhydride. 

The second cycloaddition substrate took to form of 91 (Scheme 1.9b), incorporating a vinyl sulfone dipolarophile. Beginning with cyano ketone 84, which was readily prepared from 1,5-dicyanopentane via a previously reported three-step sequence [45], condensation with thiophenol produced vinyl sulfide 85 in 84 % yield. Vinyl sulfide 85 underwent bromination in acetonitrile to afford bromo-vinyl sulfide 86 (86 %), which was then treated with isopropylmagnesium chloride [46] to effect metal-halogen exchange affording an intermediate vinyl magnesium bromide species. Subsequent alkylation with Mel in the presence of catalytic CuCN provided the alkylated vinyl sulfide 87 in 93 % yield. The nitrile within vinyl... 

Several trivial but highly useful reactions are known to convert one acceptor-substituted allene into another. For example, the transformation of allenic carboxylic acids is possible both via the corresponding 2,3-allenoyl chlorides or directly to 2,3-allen-amides [182,185], Allenylimines were prepared by condensation of allenyl aldehydes with primary amines [199]. However, the analogous reaction of allenyl ketones fails because in this case the nucleophilic addition to the central carbon atom of the allenic unit predominates (cf. Section 7.3.1). Allenyl sulfoxides can be oxidized by m-CPBA to give nearly quantitatively the corresponding allenyl sulfones [200]. The reaction of the ketone 144 with bromine yields first a 2 1 mixture of the addition product 145 and the allene 146, respectively (Scheme 7.24). By use of triethylamine, the unitary product 146 is obtained [59]. The allenylphosphane oxides and allene-... 

OL-Hydroxy aldehydes. A new method for one-carbon homologation of ketones to a-hydroxy aldehydes involves Darzens condensation with chloromethyl phenyl sulfone to give an ex,p-epoxy sulfone followed by ring opening by hydroxide ion. The anhydrous potassium hydroxide obtained by controlled addition of water to potassium /-butoxide (8,... 

Enol phosphates of a-ketosulfones provide the key intermediate to alternate schemes leading to acetylenes. Acylation of phenyl sulfones with esters affords the ketone derivatives directly. Alternately, the ketones can be obtained by Moffat oxidation of the condensation products from aldehydes with sulfone anions. Conversion to the enol derivatives followed by treatment with Na/NH or Na(Hg) gives the acetylenes. 

In an attempt to further extend the foregoing methodology to include the preparation of o,p-epoxy sulfides, the condensation of chloromethyl p-tolyl sulfide and benzaldehyde using a protocol similar to that employed successfully in the sulfone case (Bu OK) gave only poor conversion to the desired epoxide. However, addition of the hindered amine base 1,4-diazabicyclo[2.2.2]octane (DABCO) results in the formation of the isomeric expoxides (29) in good yield (equation 9). In the case of benzaldehyde, the cis-epoxide predominates over the trans-epoxide (29b 82% versus 18%), while in the corresponding condensation with pivalaldehyde, the only epoxy sulfide obtained is the cis isomer (29c). Several attempts to effect an analogous reaction with ketones were unsuccessful formation of (30) (displacement-elimination) becomes the favored process (equation 10). 

Sulfonamides as ortho-directing substituents for metalating aromatic systems opened the door to synthetic routes to cyclic sulfonic esters (sultones) and amides (sultams). The first step in this procedure for preparing sultams involved the 2-metalation of N-alkylbenzenesulfonam-ides (52) and condensation with a variety of ketones. The tertiary alco-... 

Vinyl sulfones. Both lithiation and condensation with ketones are promoted by ultrasound. 

Alternatively, N-substituted 3-phenylsulfonylindoles have been synthesized via reductive V-alkylation of orf/io-aminobenzyl sulfones with ketones followed by condensation with dimethylformaldehyde dimethylacetal and cyclization (Scheme 82) [203]. 

Random copoly(p-phenylene sulfide sulfone/ketone)s were easily prepared in high yield ( 95-99%) by the solution (NMP) condensation of sodium hydrosulfide (NaSH) with bis(4-chlorophenyl) sulfone (4,4 -dichlorodiphenyl sulfone) [80-07-9] and 4,4 -dichlorobenzophenone [98-98-2]. Copolymers with sulfone/ketone molar ratios > 25 75 were amorphous, whereas those with ratios < 25 75 were crystalline. These materials form tough, creaseable films and exhibit a linear increase in the Tg from 144 to 215°C, with increasing sulfone content (62). 

A new method for the preparation of PEMs is based on cross-linking and by thermally activated bridging of the polymer chains with polyatomic alcohols through condensation reaction with sulfonic acid functions. This was applied to sulfonated poly(ether ether ketone) (SPEEK) and some of the membranes exhibited conductivity higher than 2 x 10 S cm at room temperature. The SPEEK may potentially find applications as PEM materials for fuel cells. 

Condensation of sulfone-derived anions with ketones - including enolizable ketones - can also be brought to fruition. It must be noted, however, that in reaction 3.10 [25], some 15% of starting material 38 is recovered, probably originating from competitive deprotonation of the highly acidic a-keto hydrogen. Good 1,2-diastereocontrol is also exercised in this case. 

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