Aryl vinylation

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

Another synthesis of the cortisol side chain from a C17-keto-steroid is shown in Figure 20. Treatment of a C3-protected steroid 3,3-ethanedyidimercapto-androst-4-ene-ll,17-dione [112743-82-5] (144) with a tnhaloacetate, 2inc, and a Lewis acid produces (145). Addition of a phenol and potassium carbonate to (145) in refluxing butanone yields the aryl vinyl ether (146). Concomitant reduction of the C20-ester and the Cll-ketone of (146) with lithium aluminum hydride forms (147). Deprotection of the C3-thioketal, followed by treatment of (148) with y /(7-chlotopetben2oic acid, produces epoxide (149). Hydrolysis of (149) under acidic conditions yields cortisol (29) (181). 

Na2C03, H2O, dioxane, warm, 97% yield. Phenols can be protected under similar conditions. Amines are converted by these conditions to carbamates that are stable to alkaline hydrolysis with sodium carbonate. Carbamates are cleaved by acidic hydrolysis (HBr, MeOH, CH2CI2, 8 h), conditions that do not cleave alkyl or aryl vinyl carbonates. 

The Aggarwal group has used chiral sulfide 7, derived from camphorsulfonyl chloride, in asymmetric epoxidation [4]. Firstly, they prefonned the salt 8 from either the bromide or the alcohol, and then formed the ylide in the presence of a range of carbonyl compounds. This process proved effective for the synthesis of aryl-aryl, aryl-heteroaryl, aryl-alkyl, and aryl-vinyl epoxides (Table 1.2, Entries 1-5). 

Table 1.1 Synthesis of aryl-vinyl epoxides by use of chiral sulfide 1 a phosphazene base.

Until this work, the reactions between the benzyl sulfonium ylide and ketones to give trisubstituted epoxides had not previously been used in asymmetric sulfur ylide-mediated epoxidation. It was found that good selectivities were obtained with cyclic ketones (Entry 6), but lower diastereo- and enantioselectivities resulted with acyclic ketones (Entries 7 and 8), which still remain challenging substrates for sulfur ylide-mediated epoxidation. In addition they showed that aryl-vinyl epoxides could also be synthesized with the aid of a,P-unsaturated sulfonium salts lOa-b (Scheme 1.4). 

Aryl, Vinyl, and Alkyl Aziridines Stoichiometric Asymmetric Ylide-mediated Aziridination... 

Likewise, addition of aryl-, vinyl-, and alkyllithium reagents to tetrahydro-2-[2-(phcnylsul-fonyl)-2-(trimethylsilyl)ethenyl]-2tf-pyran followed by desilylation gives the. syn-products12 13. 

TABLE 26. Michael additions to aryl vinyl sulphoxides... 

Dialkyl cuprates may also be added to aryl vinyl sulphoxides and the resulting a-sulphinyl carbanions can be treated with various electrophiles such as aldehydes, ketones and alkyl halides (equation 350)643. 

McDowell and Stirling194 studied electronic effects upon the reactivity of aryl vinyl sulfones towards amines. Rate constants for t-butylamine addition in ethanol at 25 °C were well correlated by the Hammett equation, with p = 1.59. Comparison of this with p values for H-D exchange mentioned above191 suggested considerable carbanionic character in the transition state, perhaps in a concerted mechanism. Rates of addition of amines to alkenyl, allenyl and alkynyl p-tolyl sulfones have also been measured195. 

Aryl vinyl sulphones, reactions of 646 Aryl vinyl sulphoxides 620 optical resolution of 287 reactions of 354, 355, 360, 361, 621 Asscher-Vofsi reaction 189 Asymmetric induction 625 Asymmetric oxidation 72-78 Asymmetric reduction 78, 79 Asymmetric synthesis 824-846 Atomic orbitals 2, 3 Azetidinones 790, 791 ot-Azidoaldehydes, synthesis of 811 Azidosulphones, photolysis of 883, 884 Azosulphones, photolysis of 879 Azoxysulphones, photolysis of 879 1-Azulyl sulphoxides, synthesis of 265... 

Sulphones (coni.) allenic - see Allenic sulphones allyl - see Allyl sulphones aryl unsaturated alkyl - see Aryl unsaturated alkyl sulphones aryl vinyl - see Aryl vinyl sulphones as radiolytic products 907 bicyclic - see Bicyclic sulphones bis(/ -hydroxyalkyl) - see Bis... 

Durch Pyrolyse der aus Zimtaldehyd oder den (2-Aryl-vinyl)-alkyl- bzw. -aryl-ketonen mit Lithiumalanat erhaltlichen Komplexe werden Phenyl-cyclopropane erhalten (vgl. S. 173 u. 219). Als Nebenprodukte bilden sich gesattigte und ungesattigte offenkettige Kohlenwasserstoffe. 

Besides aryl, vinylic and acetoxy groups also migrate. Vinylic groups migrate... 

In summary then, 1,2 free-radical migrations are much less prevalent than the analogous carbocation processes, and are important only for aryl, vinylic, acetoxy, and halogen migrating groups. The direction of migration is normally toward the... 

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