205251-13-4

Upstream product

• 10147-11-2 propargyl benzene 
• 1517-82-4 (1R,2S,5R,SS)-(-)-menthyl p-toluenesulfinate 
• 98147-48-9 2-isopropyl-5-methylcyclohexyl 4-methylbenzenesulfinate 
• 1517-82-4 (-)-menthyl p-toluenesulfinate 

Downstream Products

• 205251-19-0 (R,Z)-2-benzyl-3-(p-tolylsylfinyl)propenenitrile 
• 373365-59-4 (3S,4S,5S)-3-benzyl-5-methyl-4-[(R)-p-tolylsulfinyl]-4,5-dihydro-3H-pyrazole-3-carbonitrile 
• 373365-56-1 (3S,4S)-3-benzyl-4-[(R)-p-tolylsulfinyl]-4,5-dihydro-3H-pyrazole-3-carbonitrile 

Relevant academic research and scientific papers

Asymmetric synthesis of chiral organofluorine compounds: Use of nonracemic fluoroiodoacetic acid as a practical electrophile and its application to the synthesis of monofluoro hydroxyethylene dipeptide isosteres within a novel series of HIV protease inhibitors

Two stereoselective routes to a series of diastereomeric inhibitors of HIV protease, monofluorinated analogues of the Merck HIV protease inhibitor indinavir, are described. The two routes feature stereoselective construction of the fluorinated core subunits by asymmetric alkylation reactions. The first-generation syntheses were based on the conjugate addition of the lithium enolate derived-from pseudoephedrine α-fluoroacetamide to nitroalkene 12, a modestly diastereoselective transformation. A more practical second-generation synthetic route was developed that is based on a novel method for the asymmetric synthesis of organofluorine compounds, by enolate alkylation using optically active fluoroiodoacetic acid as the electrophile in combination with a chiral amide enolate. Resolution of fluoroiodoacetic acid with ephedrine provides either enantiomeric form of the electrophile in ≥96% ee. Alkylation reactions with this stable and storable chiral fluorinated precursor are shown to proceed in a highly stereospecific manner. With the development of substrate-controlled syn- or anti-selective reductions of α-fluoro ketones 44 and 45 (diastereomeric ratios 12:1-84:1), efficient and stereoselective routes to each of the four targeted inhibitors were achieved. The optimized synthetic route to the most potent inhibitor (syn,syn-4, Ki = 2.0 nM) proceeded in seven steps (87% average yield per step) from aminoindanol hydrocinnamide 40 and (S)-fluoroiodoacetic acid, and allowed for the preparation of more than 1 g of this compound. The inhibition of HIV-1 protease by each of the fluorinated inhibitors was evaluated in vitro, and the variation of potency as a function of inhibitor stereochemistry is discussed.

(Z)-3-p-tolylsulfinylacrylonitriles as chiral dipolarophiles: Reactions with diazoalkanes

(figure presented) The dipolarophilic reactivity of enantiopure (Z)-3-p-tolylsulfinylacrylonitriles (1) has been evaluated with diazoalkanes. 3-Cyanopyrazoles are obtained when R = H, but with R = alkyl (Bn, n-Bu, and t-Bu) only one cycloadduct (4 or 5) is formed in high yield under mild conditions, therefore evidencing a complete control of the regioselectivity and the endolexo and π-facial selectivities. These reactions are a new straightforward entry to the synthesis of pyrazolines and related structures and reveal the excellent dipolarophilic features of (Z)-sulfinylacrylonitriles.

Synthesis and Dienophilic Behavior of Enantiomerically Pure (Z)-3-p-Tolylsulfinylacrylonitriles

The syntheses of enantiomerically pure (Z)-3-p-tolylsulfinylacrylonitrile (1b) and its 2-n-butyl (1a), 2-tert-butyl (1c), and 2-benzyl (1d) derivatives, by stereoselective hydrocyanation with Et2AlCN of their corresponding alkynylsulfoxides, are described. Asymmetric Diels-Alder reactions of these dienophiles with cyclopentadiene are also reported, the most significant finding being their total π-facial diastereoselectivity, controlled by the sulfur configuration, which can be readily inverted by using BF3 as a catalyst. The endo selectivity is very high for 1b under thermal and catalytic (ZnBr2) conditions and complete in the presence of BF3, whereas 1a and 1d only exhibit a complete endo selectivity in the presence of BF3.