Methyl phenyl sulfon, synthesis

Mixed homocuprates.7 Mixed cuprates (1) in which the nontransferable ligand is an a-sulfonyl carbanion are easily prepared from dimethyl sulfone or methyl phenyl sulfone (equation I), and are effective for conjugate addition to enones and for a synthesis of ketones from acid chlorides. 

Substituted nitrothiophenes serve as precursors for a variety of condensed thiophenes. The synthesis of thienopyrroles has been reviewed <85S143>. Treatment of (2-nitro-3-thienyl)methyl phenyl sulfone (497) with diethyl maleate in the presence of K2CO3 and 18-crown-6 gave the thienopyridine A -oxide (498) in 38% yield <92acs689>. The reaction apparently proceeds by Michael addition, followed by elimination of phenylsulfinate and cyclization. The starting material can be prepared by vicarious nucleophilic substitution discussed earlier. 

Nambo, M., Crudden, C.M., 2014. Modular synthesis of triaryknethanes through palladium-catalyzed sequential arylation of methyl phenyl sulfone. Angew. Chem. Int. Edit. 53, 742-746. 

Only a few practical applications of [ C]methyl phenyl sulfone have been reported so far (Figure 5.66). Representative ones illustrating the breadth of utility include reaction with allylic acetate in the presence of Pd(0) to give the respective 8,y-unsaturated derivative 244 as demonstrated with the synthesis of245 with ester 246 to furnish [ Cjmethyl ketone 24y203b sequential reaction of the dianion with a carbamate 12481 and an alkyl... 

SYNTHESIS OF <-)-(E,S)-3-(BENZYLOXY)-1-BUTENYL PHENYL SULFONE VIA A HORNER-WADSWORTHEMMONS REACTION OF (.).(S)-2-(BENZYLOXY)PROPANAL (Benzene, [[[1-methyl-3-(phenylsulfonyl)-2-propenyl]oxy]methyl]-, [S-(E)]-) from (Propanal, 2-(phenylmethoxy)-, (S)-)... 

Under the same basic conditions /ra . -l-acetoxymethyl-1-methyl-2-tosylcyclopropane generated an a-sulfonyl anion, which attacked the ester group intramolecularly and afforded 2,5-dimethyl-l-tosyl-3-oxabicyclo[3.1.0]hexan-2-ol (22) in 50% yield.Stereoselective synthesis with a chiral cyclopropyl sulfoxide was experienced when ( )-4-tolylsulfinylcyclopropane was reacted first with butyllithium and then with methyl benzoate and gave 1-benzoyl-1-[(5)-4-tolylsulfinyl]cyclopropane (23a) in 62% yield. A useful reaction took place when 2-(hy-droxymethyl)cyclopropyl phenyl sulfide was treated first with an excess of butyllithium and then with dimethylformamide and gave 2-hydroxy-l-phenylsulfanyl-3-oxabicyclo[3.1.0]hexane (24), a lactol which has been used to carry out various useful synthetic transformations. Another useful reaction occurred when cyclopropyl phenyl sulfones were treated with butyllithium followed by an acyl imidazole to give acyl cyclopropanes in decent yield. 

BICYCLOPROPYLIDENE possesses unique reactivity toward a wide range of electrophiles and nucleophilic carbenes. (E)-1-DIMETHYLAMINO-3-tert-BUTYLDIMETHYL-SILOXY-1,3-BUTADIENE is a highly reactive diene for Diels-Alder reactions, as described in an accompanying procedure for the synthesis of 4-HYDROXYMETHYL-2-CYCLOHEXEN-1-ONE via the Diels-Alder reaction with methyl acrylate. Finally, this section concludes with the preparation of DIETHYL [(PHENYLSULFONYL)METHYL]PHOSPHONATE, a reagent that is very useful for synthesis of a. -unsaturated phenyl sulfones. 

The synthesis of the CD segment 532 also started with dithiane 525. One-pot unsymmetric bisalkylation of 525 with 523 and 524 also effectively afforded coupling product 529, after methylation. Deprotection of TBS and acetonide followed by dethioketalization afforded a 2 1 mixture of 530 and 531. Treatment of 530 with HCIO4 effected epimerization to 531. Functional group manipulation converted 531 to iodide 532, which was coupled with thioacetal 533, prepared by Roush asymmetric crotylboration, to give adduct 534. The thioketal 534 was converted into 535 via reduction of ketone (dr = 1 3.5) and introduction of a phenyl-sulfone group. 

Another example for the application of the methodology in the chemistry of nitroarenes is the synthesis of fluorine-containing indoles. It has been shown that substitution of hydrogen H-6 in 3-fluoro-4-/ -substituted nitrobenzenes by the action of vicarious chloromethyl phenyl sulfone proceeds selectively in DMSO in the presence of KOH at room temperature to give 4-/ -3-fluoro-6-(phenylsulfonyl-methyl)nitrobenzenes in 60-70% yields (Scheme 23) [101]. 

Introduction of arylsulfonylmethyl substituents into nitroheteroaromatic rings is of great practical value because these sulfones are versatile intermediates in organic synthesis. Nitrobenzyl aryl sulfones and their heterocyclic analogues can easily be transformed into the corresponding ethenyl derivatives by a simple alkylation with simultaneous elimination of arylsulfinate anion [125]. Diethyl methylenemalonate substituent can be introduced in the positimi 4- of 5-nitroimidazole via the VNS reaction of 5-nitroimidazole with the carbanion of chloromethyl phenyl sulfone [112, 124], followed by condensation of the obtained 4-(phenylsulfonyl)methyl derivative with diethyl bromomalonate or diethyl ketomalonate (Scheme 33) [126]. 

M. Shi and Y.-L. Shi reported the synthesis and application of new bifunctional axially chiral (thio) urea-phosphine organocatalysts in the asymmetric aza-Morita-Baylis-Hillman (MBH) reaction [176, 177] of N-sulfonated imines with methyl vinyl ketone (MVK), phenyl vinyl ketone (PVK), ethyl vinyl ketone (EVK) or acrolein [316]. The design of the catalyst structure is based on axially chiral BINOL-derived phosphines [317, 318] that have already been successfully utilized as bifunctional catalysts in asymmetric aza-MBH reactions. The formal replacement of the hydrogen-bonding phenol group with a (thio)urea functionality led to catalysts 166-168 (Figure 6.51). 

One Sanofi synthesis of enantiomerically pure (-i-)-clopidogrel (2) utilized optically pure (R)-(2-chloro-phenyl)-hydroxy-acetic acid (20), a mandelic acid derivative, available from a chiral pool. After formation of methyl ester 21, tosylation of (/ )-21 using toluene sulfonyl chloride led to a-tolenesulfonate ester 22. Subsequently, the Sn2 displacement of 22 with thieno[3,2-c]pyridine (8) then constructed (-i-)-clopidogrel (2). Another Sanofi synthesis of enantiomerically pure (-i-)-clopidogrel (2) took advantage of resolution of racemic a-amino acid 23 to access (S)-23. The methyl ester 24 was prepared by treatment of (S)-23 with thionyl chloride and methanol. Subsequent Sn2 displacement of (2-thienyl)-ethyl para-toluene-sulfonate (25) assembled amine 26. 

In the stepwise synthesis of the unsymmetrical complex dye 13 [ 70236-60-1] [10], the azo dye made from diazotized l-amino-2-hydroxy-5-nitrobenzene and 1-phenyl-3-methyl-5-pyrazolone and the 1 1 chromium complex obtained from 6-nitro-l-diazo-2-hydroxynaphthalene-4-sulfonic acid and 2-naphthol are heated together at 80 °C for 5 h. The adduct is salted out with NaCl. A black powder is obtained that dyes wool and leather in dark brown shades. The resulting colors are fast, particularly on shrink-resistant wool. 

---