Carbonyl addition, epoxide ring opening

Condensation of the carbonyl group with the yUde from trimethylsulfonium iodide leads initially to an addition product. The anion formed on the carbonyl oxygen then internally displaces dimethyl sulfide to give an oxirane yielding epoxide (114-3). Reaction of that intermediate with a 1,2,4-triazine leads to an epoxide ring opening with the consequent incorporation of the second heterocyclic moiety. There is thus obtained fluconazole (114-4) [125]. 

The homopol5unerization of diisocyanates is only useful for specialty diisocyanates, such as aliphatic 1,2- or 1,3-diisocyanates (3) and aromatic o-diisocyanates (4), which polymerize via cycloaddition processes. Anionic homopolymerization of monoisocyanates takes place by addition across the 0=N bond to form nylon-1 polymers. Polyamides are also obtained fi"om diisocyanates and enamines or ketenaminals. This reaction proceeds by a [2 -i- 2] cycloaddition reaction with subsequent ring opening to form polyamides. [2 - - 4] cycloaddition polymerization to form heterocyclic polymers is observed with carbonyl diisocyanate (5). Ring-opening polymerization occurs in the reaction of bis-epoxides... 

Amines can be prepared using reactions including epoxide ring opening, addition of nitrogen nucleophiles to carbonyls followed by reduction, reduction of amides, reduction of nitriles, and nitration of arenes followed by reduction. 

The pathway by which the reactions are considered to occur involves attack of the enolate anion at the 1 0 bond of o-iodosyl benzoic acid followed by reductive elimination of o-iodobenzoic acid upon addition of methoxide to the carbonyl group. Ring opening of the epoxide thus formed yields the hydroxy dimethyl acetal ... 

Until now, three main F-C transformations have been used for catalytic stereoselective formation of benzylic carbon stereocenters - 1,2-addition of arenes to carbonyl (C=X, X O, NR) moieties, 1,4-addition of arenes to electron-deficient C-C double bonds, and ring-opening reaction of epoxides. 

Because the reaction conditions are basic, the next thing to do is to search for protons in the molecule that are acidic and for carbons susceptible to reaction with a nucleophile. At this point, we will look at possible nucleophilic reactions and will return to acidic protons later in the discussion. Two obvious electrophilic carbons are those of the epoxide. Moreover, if the C-2—C-7 bond is formed by nucleophilic reaction of an anion at C-2 on carbon C-7, ring opening of the epoxide would also occur in this step. This ring opening would be a driving force for the reaction. Thus, we should search for steps that would lead to an anion at C-2. This is not likely to be obvious from initial inspection of the product. In addition to the epoxide carbons, electrophilic positions in 7-16 include the carbonyl carbon (C-1) and the positions )8 and S to it (C-3 and C-5). 

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