A-/3-Ethylenic sulfoxides

During the past three years, we have had excellent success in achieving some asymmetric syntheses O). We have focused attention specifically on faithful transfer of chirality from the sulfur atom of some a-carbonyl a,3-ethylenic sulfoxides to the 3-carbon atom during organometalllc 3-addition reactions. This type of high asymmetric induction in forming carbon-carbon bonds has led to successful preparation of several classes of optically active synthetic intermediates such as 3-methylalkanoic acids and 3-methylcycloalkanones. In addition, this asymmetric methodology has been applied successfully to preparation of more complex, enantiomerically pure molecules such as steroids and steroid intermediates. 

The first literature report of asymmetric 3-addition to an enantiomerically pure a,3-ethylenic sulfoxide appeared in 1971 and involved 3-addition of piperidine to propenyl sulfoxide X (eq. 1) (6), The absolute stereochemistry of this reaction was rationalized by Stirling in terms of transition state la in which the nucleophile approached the 3-carbon atom on that side of the double bond remote from the bulky tolyl group in the conformation shown in model Xs (O ... 

Carboxylation of such a 1-lithio 1-alkenyl sulfoxide led to a diastereomerically and enantiomerically pure a-carboxyl a,3-ethylenic sulfoxide such as after protonation of the intermediate lithium carboxylate and to the corresponding methyl ester 5fe after methylation with methyl iodide-hexamethyIphosphoramide (HMPA) (eq. 6) ( ). 

Addition to ei,fi-acetylenic sulfoxides. Methylcopper reacts with a, -iicctylenic sulfoxides (1) by c(s-addition to give 3-methyl-a,/3-ethylenic sulfoxides (2) in high yield q... 

A different approach to solving this problem is to attach a chiral auxiliary to the enone substrate. The auxiliary is a chiral material that is attached to an achiral substrate. The asymmetry of the auxiliary controls the selectivity of the reaction and is then removed in a separate chemical step. Posner studied the use of optically pure a-carbonyl-a, 3-ethylenic sulfoxides (465, see sec. 3.9.A.ii for the preparation of optically active sulfoxides)." 29 Conjugate addition of di-(2,2,-dimethylpropyl)magnesium cuprate to the chiral... 

Cycloaddition of nitrones and of nitrile oxides to a, /J-ethylenic sulfoxides have been recorded102. 

The direct combination of selenium and acetylene provides the most convenient source of selenophene (76JHC1319). Lesser amounts of many other compounds are formed concurrently and include 2- and 3-alkylselenophenes, benzo[6]selenophene and isomeric selenoloselenophenes (76CS(10)159). The commercial availability of thiophene makes comparable reactions of little interest for the obtention of the parent heterocycle in the laboratory. However, the reaction of substituted acetylenes with morpholinyl disulfide is of some synthetic value. The process, which appears to entail the initial formation of thionitroxyl radicals, converts phenylacetylene into a 3 1 mixture of 2,4- and 2,5-diphenylthiophene, methyl propiolate into dimethyl thiophene-2,5-dicarboxylate, and ethyl phenylpropiolate into diethyl 3,4-diphenylthiophene-2,5-dicarboxylate (Scheme 83a) (77TL3413). Dimethyl thiophene-2,4-dicarboxylate is obtained from methyl propiolate by treatment with dimethyl sulfoxide and thionyl chloride (Scheme 83b) (66CB1558). The rhodium carbonyl catalyzed carbonylation of alkynes in alcohols provides 5-alkoxy-2(5//)-furanones (Scheme 83c) (81CL993). The inclusion of ethylene provides 5-ethyl-2(5//)-furanones instead (82NKK242). The nickel acetate catalyzed addition of r-butyl isocyanide to alkynes provides access to 2-aminopyrroles (Scheme 83d) (70S593). 

Commercial Sodium Acetylide A suspension (30 ml) of sodium acete-lide (20% in exylene) is centrifuged and the solid brown sodium acetylide is taken up in 25 ml of dimethyl sulfoxide. To this is added a solution of 5 g of 5a-hydroxy-6j5-methylandrostane-3-17,dione 3-ethylene ketal in 85 ml of dimethyl sulfoxide. After stirring at room temperature overnight, ice is added and the solution diluted to about 250 ml. The tan precipitate is collected, washed with water and dried yield 4.8 g mp 202-204°. Crystallization from ethyl acetate gives a product of mp 204-206°. 

In general, synthesis of 4-isoxazolines is accomplished via three routes 1,3-dipolar cycloaddition of nitrones to alkynes or by the oximation of a,i -ethylenic ketones, a-alkynic ketones and aldehydes or from the selective reduction of isoxazolium salts. The nitrone (262) underwent tandem cyclo-addition-[2,3]sigmatropic rearrangement with allenyl sulfoxide (263). And it resulted in 4-isoxazoline (264) (Equation (46)) <89TL663>. 

One of the earliest nucleophilic reactions of ethylene cyclic sulfite was reported with phenylmagnesium bromide (56JA454). Depending on the reaction conditions, a 3.4 to 23% yield of bromohydrin and a 42-60% yield of diphenyl sulfoxide were isolated [56CI(L)490j. 

Extension of the above method to 3-methoxyestra-3,5(10)-dien-17-one 17-ethylene ketal (46) prepared by base-catalyzed isomerization of 3-methoxy-estra-2,5(10)-dien-17-one 17-ketal (42) with potassium t-butoxide in dimethyl sulfoxide gives the isomeric tropone A-homo-estra-l,4,5(10)-triene-3,17-dione... 

Other polydentate ligands are polyamines and related ligands. Stability constants of silver(I) complexes with polyamines in dimethyl sulfoxide,419 A-methyl-substituted 4-methyldiethylene-triamines,420 or ethylene- or N- or C-methylated ethylenediamine in aqueous solution have been reported.421 The structure of the silver 1,3-diaminopropane complex, [Ag NH2(CH2)3NH2 ]-C104,422 and complex formation with 1,4-diaminobutane and 1,5-diaminopentane have been reported.423 A dinuclear silver(I) compound with ethylenediamine [(enH)Ag(en)Ag(enH)2]4+ has... 

For the addition of ethylene, EtOAc as solvent was particularly advantageous and gave 418 in 60% yield (Scheme 6.86). The monosubstituted ethylenes 1-hexene, vinylcyclohexane, allyltrimethylsilane, allyl alcohol, ethyl vinyl ether, vinyl acetate and N-vinyl-2-pyrrolidone furnished [2 + 2]-cycloadducts of the type 419 in yields of 54—100%. Mixtures of [2 + 2]-cycloadducts of the types 419 and 420 were formed with vinylcyclopropane, styrene and derivatives substituted at the phenyl group, acrylonitrile, methyl acrylate and phenyl vinyl thioether (yields of 56-76%), in which the diastereomers 419 predominated up to a ratio of 2.5 1 except in the case of the styrenes, where this ratio was 1 1. The Hammett p value for the addition of the styrenes to 417 turned out to be -0.54, suggesting that there is little charge separation in the transition state [155]. In the case of 6, the p value was determined as +0.79 (see Section 6.3.1) and indicates a slight polarization in the opposite direction. This astounding variety of substrates for 417 is contrasted by only a few monosubstituted ethylenes whose addition products with 417 could not be observed or were formed in only small amounts phenyl vinyl ether, vinyl bromide, (perfluorobutyl)-ethylene, phenyl vinyl sulfoxide and sulfone, methyl vinyl ketone and the vinylpyri-dines. 

The reaction of the p-nitrophenyl esters with the polymer (4) was studied in dimethyl sulfoxide ( DMSO ) solution in the presence of triethylamine at 25°C. The poly-L-lysine derivatives obtained have different IR absorption spectra from those of the starting compounds, and have absorptions assigned to the nucleic acid bases. Poly( e,N-Ade-L-lysine )(5) was soluble in DMSO and ethylene glycol, and also in water below pH 3, where it was present as a protonated form. In dimethylformamide (... 

Thus, a-sulfinyl lithium carbanion of 1-chloroethyl p-tolyl sulfoxide was reacted with 1,4-cyclohexanedione mono ethylene ketal (195) to afford the adduct (196) in quantitative yield. The adduct was treated with ferf-butylmagnesium chloride (magnesium alkoxide was initially formed) followed by isopropylmagnesium chloride to result in the formation of magnesium /3-oxido carbenoid 197. The /3-oxido carbenoid rearrangement then takes place to give one-carbon expanded magnesium enolate 198. Finally, an electrophile was... 

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