Cyclic enones acetals

Addition of azide ion to conjugated systems can be carried out by using NaN3 and acetic acid in water (Eq. 10.18).38 Some reactions were very rapid while others took 1 to 3 days to complete. Lewis base was found to catalyze such conjugate additions of azide ion to cyclic enones in water.39... 

Merritt et al. [124,170-174] carried out some of the earliest additions of fluorine to carbon-carbon double bonds. The fluorination of cis and trans propenyl benzene in a nonpolar solvent at low temperature gave predominantly erythro and threo difluorides respectively. More recently, Rozen [175] carried out similar reactions, but used a more polar solvent (trichlorofluoro methane, chloroform and ethanol) and a very low concentration of fluorine. Thus, in the fluorination of cis and trans 3-hexene- l-ol acetate (Fig. 72), syn addition occured to give exclusively the erythro and threo difluoro compounds respectively. Corresponding results were obtained in the addition of fluorine to other alkenes, including cyclic alkenes and cyclic enones. 

These two intermediates 54 and 55 each have a 1,5-diCO relationship that can be disconnected in two ways. Both 54b and 55b disconnect a ring bond and give unsimplified starting materials 56 and 59. But the others 54a and 55a achieve some simplification and suggest simple cyclic enones 57 and 60 in combination with enol(ate)s of acetone 58 or an acetate ester 61. These are much more promising and we shall come back to them. 

Heteroaromatic aldehydes are excellent electrophiles in the MBH reaction because of their increased electrophilicity. The heteroatom also facilitates the proton transfers involved in the reaction (Scheme 1.53)/ In the presence of DABCO, pyridine-2-carboxaldehyde derivatives react rapidly with acrylates, methyl vinyl ketone and acrylonitrile to give excellent yields of the MBH adducts 112, which can be further transformed into indolizines 114 by thermal cyclization of their acetate derivatives 113 (Scheme 1.54)/ Notably, a small amount of indolizine 114 was formed along with normal MBH adduct 112 in the reaction of pyridine-2-carboxaldehyde with methyl vinyl ketone. Similarly, substituted 2-chloronicotin aldehydes 115 are reactive and efficient in the MBH reaction of methyl acrylates, acrylonitrile and cyclic enones catalyzed by various tertiary amine catalysts, such as DABCO, DBU, imidazole and 1-methylimidazole, to provide novel MBH adducts 116 and 117 for biological activity screening (Scheme 1.55). ... 

In the presence of TMSOTf, BFs.OEtz and dimethyl sulfide, the iminium ions 204 (masked as N,0-acetals) have been employed to couple with a very board range of readily available Michael acceptors, including acrolein and acrylates, in both an inter- and intramolecular MBH-type reaction to give densely functionalized heterocycles 207 (Scheme 1.78). The process has been rendered asymmetric and high enantioselectivity is obtained in reactions of iminium ions 210 (masked as N,0-acetals) and cyclic enones (Scheme 1.79). Finally, the usefulness of the methodology has been exemplified in a short synthesis of ( + )-heliotridine 208 and (-)-retronecine 209 (Scheme 1.78). ... 

Basavaiah et al. have developed a similar domino Michael-Mukaiyama-retro-aldol process of cyclic enones with acetals, which conveniently were promoted by mixing a sulfide, TBDMSOTf, in the presence of the Hiinig s base. 

A nickel-catalyzed carbozincation in which an allylzinc adds across the double bond of an unsaturated acetal has also been reported (Scheme 79). ] This procedme effectively provides a reverse-polarity approach to the functionalization of unsaturated carbonyl derivatives. Non-allylic Grignard reagents, however, add to cychc unsaturated acetals with the opposite regiochemistry. This latter procedure provides the basis for an enantioselective conjugate addition to cyclic enones (in 53% ee for the cyclopentenyl substrate and 85% ee for the cyclohexenyl homologue). ... 

The photochemical reactivity of P-ketoesters is different form that of P-diketones. Irradiation of a P-ketoester in the presence of an alkene produces oxetane via the ketone carbonyl instead of the desired cyclobutane ring system. Therefore, it is necessary to covalently lock the ketoesters as the enol tautomers. To this end, silyl enol ethers, 129 and 132a, and enol acetates, 130 and 132b, were prepared, but these substrates still fail to undergo the desired intramolecular [2 + 2] photocycloaddition with olefins. The only new products observed in these reactions result from the photo-Fries rearrangement of the cyclic enol acetate (130 to 131) and cis-trans isomerization of both acyclic substrates 132a/b. However, tetronates are appropriate substrates for both intermolecular and intramolecular photocycloadditions with olefins. In addition, enol acetates and silyl enol ethers of p-keto esters are known to undergo [2 + 2] photoaddition with cyclic enones (vide infra). 

Addition of organocuprate reagents to a,j8-enones is solvent dependent indeed the addition is retarded by the inclusion of HMPA in the reaction medium to the extent that halide-ion displacement occurs preferentially. " Copper-catalysed conjugate addition of the magnesio-acetal (25) to cyclic enones is the key step in a new cyclopentene annelation procedure [equation (36)]. ... 

Rate constants for interaction of triplet excited states of cyclic enones with alkenes were first reported by Schuster et al. > > using transient absorption spectroscopy (nanosecond flash photolysis). The rate constants were obtained from the relationship (Xx)" = ( o) + (alkene), where Xq is the limiting triplet hfetime of the enone at a given concentration in the absence of alkene. The decay of enone triplet absorption at 280 nm could be conveniently followed upon excitation of the enones (cyclopentenone [CP], 3-methylcyclohexenone [3-MCH], testosterone acetate [TA], and BNEN [4] were aU studied]) in acetonitrile and cyclohexane at 355 nm using the third harmonic of a Nd YAG laser. In aU cases, triplet decays were clearly first order. Quantum efficiencies for capture of enone triplets by alkenes (O,.) are given by fc x (alkene) using the experimentally determined values of and Xq,... 

Entries 10 to 14 show reactions involving acetals. Interestingly, Entry 10 shows much-reduced stereoselectivity compared to the corresponding reaction of the aldehyde (The BF3-catalyzed reaction of the aldehyde is reported to be 24 1 in favor of the anti product ref. 80, p. 91). There are no stereochemical issues in Entries 11 or 12. Entry 13, involving two cyclic reactants, gave a 2 1 mixture of stereoisomers. Entry Mis a step in a synthesis directed toward the taxane group of diterpenes. Four stereoisomeric products were produced, including the Z E isomers at the new enone double bond. 

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