John S. Swenton

Intramolecular anodic carbon-carbon bond-forming reactions of oxidized phenol intermediates leading to spirodienones. Structural effects on reactivity and evidence for a phenoxonium ion intermediate

Anodic oxidation of 4-phenylphenol in methanol leads to 4-methoxy-4-phenylcyclohexa-2,5-dienones whereas anodic oxidation of 4-(2-alkenylphenyl)-phenols leads to spirocyclic 2,5-cyclohexadienones in competition with methanol addition to the 4-position. Using 4-phenylphenol and -1-(2-propenylphenyl)phenol as model systems, the optimum conditions for solvent addition versus carbon-carbon bond formation have been studied. The yield of the anodic cyclization reaction shows a dramatic dependence on olefin structure. Whereas 4-(2-propenylphenyl)phenol gives the spirocyclic 2,5-cyclohexadienone in high yield, 4-(2-vinylphenyl)phenol affords the analogous product in only 16% yield

A convergent synthesis of (+)-4-demethoxydaunomycinone and ( + )-daunomycinone

Abstract A convergent synthesis of (+)-4-demethoxydaunomycinone and (+)-daunomycinone via annelation of a functionalized quinone monoketal with the anion of the corresponding 3-cyano-l(3H)isobenzofuranone is reported. The quinone monoketal, sequence, was prepared without chromatography from 2,5-dimethoxybenzaldehyde in sixteen steps. The monoketal of proper absolute configuration was obtained by resolution of the imine from (−)-α-methylbenzylamine and 1,2,3,4,-tetrahydro - 5,8 - dim cyclic 4-(ethylene mercaptole).Two noteworthy aspects of the synthesis were the highly selective reduction of a bicyclic β-hydroxyketone to afford a diol with the required cis -stereochemistry at the eventual C-7 and C-9 positions of the anthracyclinone and the regioselective hydrolysis of the quinone bisketal to afford the monoketal of proper regiochemistry for the synthesis of( + )-daunomycinone. Thus, ( + )-daunomycinone and (+)-4-demethoxydaunomycinone were prepared in nineteen steps from 2,5-dimethoxybenzaldehyde in respective overall yields of 3 and 5% (the overall yield for the racemic material was 13%). This synthetic strategy allows a convergent approach to a variety of D-ring analogs.

Spiro-annulated 2,5-cyclohexadienones via oxidation of 2′-alkenyl-p-phenyl phenols with iodobenzene diacetate

Abstract The oxidation of 2′-alkenyl-substituted p-phenyl phenols via iodobenzene diacetate gives spiro-annulated-2,5-cyclohexadienones.

Dihydrobenzofuran derivatives via the anodic cycloaddition reaction of p-methoxyphenols and vinyl sulfides

Abstract The anodic oxidation of p-methoxyphenols in the presence of vinyl sulfides gives high yields of dihydrobenzofurans arising via a formal 1,3-cycloaddition reaction of the vinyl sulfide and the anodically generated phenoxonium ion.

Intramolecular cyclization of 2'-olepinic side-chains on anodically oxidized 4-phenylphenols. The effect of olefin substituents on carbon—carbon bond formation

Abstract The anodic oxidation of 4-(2′-alkenyfphenyl)phenols in acetonitrile/methanol affords spirodienones arising from cyclization of the olefinic side-chain to the 4-position of the phenol and reaction of the resulting benzylic cation with methanoi. The efficiency of this carbon—carbon bond-forming reaction is dependent upon the olefinic substituents.

Competitive hydrogen and carbomethoxy migration in the photochemistry of 7-carbomethoxy-3,4-benzotropilidene

Abstract The preparative photolysis of 7-carbomethoxy-3,4-benzotropilidene (7) in cyclohexane at 300–380 nm yields 6-carbomethoxy-2,3-benzonorcaradiene (11) 51%; 7-carbomethoxy-2,3-benzonorcaradiene (5) 35%; and 6-carbomethoxy-2,3-benzobicyclo[3.2.0]hepta-2,6-diene (6) 14%; as photoproducts. Deuterium labeling has established that the major product (11) arises from a formal 1,7-hydrogen shift, while 5 is formed by a formal 1,7-carbomethoxy migration. A substantial isotope effect was noted in the photolysis of the 7-deutereo-7-carbomethoxy-3,4-benzotropilidene. Mechanisms are discussed for the direct production of 6 from 7. Multiplicity studies indicate that these reactions of 7 occur from the excited singlet state and quantum yield determinations demonstrate that the overall reactive process is highly efficient.

Spirodienones via a thermal uncatalyzed [1,3]-oxygen-to-carbon migration

Abstract Exocyclic vinyl ethers derived from p -quinols, readily available from aryllithium addition to quinone monoketals, undergo high-yield thermal [1,3]-oxygen-to-carbon migration, yielding spirodienones.

Anodic oxidation studies of oxygenated biphenyls. Convenient synthetic routes to certain functionalized biphenyls

Abstract The anodic oxidation of oxygenated biphenyls produces phenyl-substituted p -quinol ether ketals in good-to-excellent yield. These compounds are useful substrates for preparation of more highly functionazized biphenyls.

Photochemical processes in substituted 3,4-benzotropilidenes

Abstract The products and quantum yields from direct irradiation of 7-methyl-, 7,7-dimethyl-, 7,7-dicarbomethoxy-, and the unsubstituted 3,4-benzotropilidene have been determined. The major process of these excited 3,4-benzotropilidenes is formal 1,7-group migration to produce a benzonorcaradiene. In the case of the unsubstituted molecule and the 7,7-dimethyl derivative a minor process involving 1,3-hydrogen or methyl shift to produce a 1,2-benzotropilidene was characterized. The uniformly high quantum efficiencies for these reactions (Φ = 0·37–0·92) indicate that group migration is the dominant process for decay of the 3,4-benzotropilidene excited states.

Spiro-annulated cyclohexa-2,5-dienones via electrooxidation of p-aryl phenols a novel mode of anodic carbon-carbon bond formation

Abstract Intramolecular trapping of the reactive intermediate from anodic oxidation of 2′-alkenyl substituted p -aryl phenols, followed by solvent capture, affords 4-aryl-4-alkyl-cyclohexa-2,5-dienones.