Stiles reaction

Problem 3.13. In the Stiles reaction, the highly reactive compound benzyne is obtained by treatment of anthranilic acid (2-aminobenzoic acid) with NaNC>2 and HC1. Draw a mechanism for this reaction. 

Pyridyne is formed and reacts as a dienophile in reactions analogous to those described by Wittig and Pohmer and by Stiles and Miller in benzyne chemistry. ... 

The Stiles-Sisti reaction (Scheme 12-17) is an azo coupling reaction in which an a-hydroxyalkyl residue is the electrofugic leaving group (Stiles and Sisti, 1960 Sisti et al., 1962). The reaction is used to prepare aldehydes and ketones (e. g., 2-methoxy-... 

The addition of phosphine to olefins provides today a generally applicable method for the syntheses of organophosphines. Stiles, Rust and Vaughan were the first to study the reaction systematically. It is catalysed by organic peroxides such as, for example, di-t-butyl peroxide, by a, a -azobis-isobutyro-nitrile by other free radical sources or by exposing the reaction mixture to UV- or X-radiation. The PHj radicals, produced according to Eq. (77), react further with olefins thus producing PH2 radicals continually. 

Stiles and coworkers (70) have taken advantage of the effect of chelation to carboxylate compounds having active methylene groups. The reactions of these substances with C02 in the presence of aluminum or magnesium alkoxide readily produce chelate products (Equations 23 and 24). 

Scheme 1. Endgame to the immunosuppressive natural product sanglifehrin A (1) from Streptomyces Jlaveolus. Nicolaou et al. and Paquette et al. connect the same building blocks 2 and 3 by Stile coupling reactions, followed by ketal hydrolysis. Strategic connections for the synthesis of 2 and 3 are given (see following Schemes).

Biphenyl, benzocyclooctatetraene (9), and benzobicyclo[2,2,2]octatriene (10) resulted from the reaction of benzyne (by decomposition of benzene-diazonium carboxylate) with benzene at 45° (Miller and Stiles, 1963). Both 9 and 10 have been found to go to naphthalene and acetylene 9 on photolysis (Fonken, 1963), and 10 in a sealed tube at 300° (Miller and Stiles, 1963). 

A carbonic acid derivative which, surprisingly, also proves to be suitable for the acylation of ketone enolates, is Stiles reagent, i.e., (methoxymagnesium) monomethyl carbonate. In Section 8.2, you saw how this reagent can be obtained. Ketone enolates are carboxylatedby Stiles reagent to furnish a /3-keto carboxylic acid, as shown by the reaction equation below. As this keto acid is initially obtained as the (methoxymagnesium) carboxylate, such an acylation can easily proceed without the extra equivalents of enolate or base mentioned above. 

Based on the research work of Stiles (1952), one of the most important phosphorus ester insecticides, 0,0-dimethyl-0-[(l-methyl-2-carbomethoxy)vinyl] phosphate (mevinphos, 73) was introduced in 1957 under the trade name Phosdrin . It is prepared by the Perkow reaction from trimethyl phosphite and methyl a-chloroacetoacetate. 

The decarboxylation of diazotized anthranilic acid carried out by Stiles and Miller49 is also a fragmentation reaction it affords dehydrobenzene (benzyne), which reacts at once as a dienophile with, e.g., furan, giving 1-naphthol by way of an epoxide. 

The key step of the synthesis of spirotryprostatin B (133) by Trost and Stiles is an enantioselective Pd-catalysed decarboxylation-allylation reaction starting from the prenyl p-oxoester 145, which serves as a pre-nucleophile (Scheme 29) [124]. 

P.J. Stiles, D.F. Fletcher, I. Morris, The effect of gravity on the rate of a simple liquid-state reaction in a small unstirred cylindrical vessel (II), Phys. Chem. Chem. Phys., 2001, 3, 3651-3655. 

The rate of drying is an important factor because a thin film of moisture with high oxygen concentration promotes reaction. For normal exposure conditions, the films dry quite rapidly, and it is only in sheltered areas that drying times are so slow that the attack of zinc is accelerated significantly. Stiles and Edney (1989) have studied thin acidified films of water to show a steady rate of dissolution of zinc until the acidity is destroyed. 

In the last quarter of the 20th century a new family of C-C forming reactions based on transition metal catalysts evolved as powerful tools in synthesis. Palladium-catalyzed cross-coupling reactions (Heck, Stile, Suzuki) and metathesis of olefins, enynes, and alkynes have had a profound impact on the art of total synthesis. 

Stiles, M., Wolf, D. and Hudson, G.V., Catalyst selectivity in the reactions of unsymmetrical ketones reaction of butanone with benzaldehyde and p-nitrobenzaldehyde, /. Am. Chem. Soc., 1959,81,628-632. 

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