Sodium phenylsulfinate

Work at Rhc ne-Poulenc has involved a different approach to retinal and is based on the paHadium-cataly2ed rearrangement of the mixed carbonate (41) to the aHenyl enal (42). Isomerization of the aHene (42) to the polyene (43) completes the constmction of the carbon framework. Acid-catalyzed isomerization yields retinal (5). A decided advantage of this route is that no by-products such as triphenylphosphine oxide or sodium phenylsulfinate are formed. However, significant yield improvements would be necessary for this process to compete with the current commercial syntheses (25—27) (Fig. 9). 

Chloro-5-phenyl-l,3,4-thiadiazole 52 reacts with thiourea in refluxing ethanol to afford the thione 61 (Equation 11) <2000MI31>. The reaction of sodium phenylsulfinate with thiadiazole 62 in refluxing dimethylfor-mamide (DMF) gave the 5-phenylsulfonyl-l,3,4-thiadiazole 63 (Equation 12) <1999AF1035>. 

The addition of sodium phenylsulfinate nucleophiles to stereodefined acyclic allylic chlorides was reported to proceed with complete overall retention of configuration, indicating that this nucleophile adds with inversion of configuration, i.e. via attack at the allyl ligand (equation 193).21S A cyclohexenyl acetate substrate also showed predominant ligand addition, but some isomeric product was also produced (equation 194).216 This loss could be due to acetate epimerization of starting material, ir-allyl epimeriza-tion by PdL2, or by attack of the sulfur at the metal, followed by reductive elimination. 

This overall synthetic strategy (see Figure 11.8) was adapted to give a range of isomeric pyrido[2,3-/z]pyrazincs structures 34 by simply varying the order of reaction with appropriate mono- and difunctional nucleophiles [57, 58] (see Table 11.6). For example, reaction of sodium phenylsulfinate with pentafluoropyridine gives the... 

In 1977, de Waard at the University of Amsterdam conceived and prosecuted a novel approach that he dubbed the Michael-induced Ramberg-Backlund (MIRB) olefin synthesis. 24,25 The reaction of dienyl sulfone 25 with one equivalent of sodium phenylsulfinate produced the Michael-induced Ramberg-Backlund product 26 in 40% yield. 

SCHEME 5.20 Nucleophilic substitution chemistry with sodium phenylsulfinate [21]. 

The synthesis of 4,5-dicyano-l,2,3-trithiole 2-oxide (172) starts from sodium cyanide and carbon disulfide which via (170) gave the disodium salt of 2,3-mercaptomaleonitrile (171 M = Na). Treatment of the corresponding silver salt (171 M = Ag) with thionyl chloride yielded (172) <66HC(2l-l)l). Phenylsulfine (174), prepared in situ by dehy-drohalogenation of phenylmethanesulfinyl chloride (173), slowly decomposed in ether solution at room temperature to give cis- and trans-stilbenes, mms-4,5-diphenyl-l,2,3-trithiolane 1,1-dioxide (36) and a 5,6-diphenyl-l,2,3,4-tetrathiane dioxide (68JCS(C)1612). The mechanisms of formation of these heterocycles are obscure. 

Joule then expanded this chemistry to include intramolecular cyclizations of amines [40]. In the presence of sodium hydride, the amide 79 underwent addition to C-3. Expulsion of phenylsulfinate and tautomerization yielded the ketone 80 in 80% yield. Deprotection with sodium hydroxide yielded the free amine 81 in 85% yield. Reactions of this style provided access to the alkaloids, hydroxycryptolepine, cryptolepine, and quindoUne (83). 

Sodium sulfite and phenylsulfinate have been used as nucleophiles to produce the corresponding trisubstituted olefins 331 and 332, respectively, when using bromo-MBH adducts as substrate." Compound 331 is an important synthon for orally active renin inhibitor A-72517 (Scheme 3.144). 

Preparation from thioxanthen-9-one 10,10-dioxide (SM) by a three-steps synthesis refluxing SM in 2% sodium hydroxide-65% dioxane-water solution for 4 h gave the 2-(2-hydroxybenzoyl)-phenylsulfinic acid (25%). The former, by reaction with mercuric chloride in refluxing aqueous acetic acid for 4 h, led to the 2-chloromercuri-2 -hydroxybenzophenone (69%). Removal of the chloromercury group was achieved with concentrated hydrochloric acid in refluxing ethanol for 2 h (91%) [62],... 

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