Geminal acylation

Steven K. Davidsen, Gerald W. Phi 11ips, and Stephen F. Martin 119 GEMINAL ACYLATION-ALKYLATION AT A CARBONYL CENTER USING DIETHYL N-BENZYLIDENEAMINOMETHYLPHOSPHONATE PREPARATION OF 2-METHYL-2-PHENYL-4-PENTENAL... 

Table I. Geminal Acylation-Alkylation of Carbonyl Compounds... 

D.J. Burnell et al. synthesized bicyclic diketones by Lewis acid-promoted geminal acylation involving cyclic acyloins tethered to an acetal. The required b/s-silyloxyalkenes were prepared by using the standard acyloin condensation conditions. ... 

Davidsen, S.K., Phillips, G.W., and Martin, S.F., Geminal acylation-alkylation at a carbonyl center using diethyl IV-benzylideneaminomethylphosphonate. Preparation of 2-methyl-2-phenyl-4-pentenal (4-Pentenal, 2-methyl-2-phenyl-), Org. Synth., 65, 119, 1987 Org. Synth. Coll. Vol. VIII, 451, 1993. 

Table 4 Geminal Acylation/Hydroxyalkylation of Carbonyl Compounds (Scheme 7)...

Schmalz and coworkers recently reported an interesting and highly efficient Au(I)-catalyzed cascade cycloisomerization of geminal acyl-alkynylcydopropanes 102 into the densely functionalized furans 103(Scheme 8.41) [160]. This reaction proceeded under very mild reaction conditions and a variety of nucleophiles, such as alcohols, including tert-butanol, phenols, acetic acid, 2-pyrrolidone, and indole could be employed. In addition, this transformation was shown to be catalyzed by Cu(II)-and Ag-trifiates, albeit with somewhat lower efficiency. Two mechanisms, including concerted and stepwise formation of a furan ring, were proposed by the authors for this cascade transformation (Scheme 8.42). 

The generation and reaction of metalloenamines is central to a method for geminal acylation and alkylation at the carbonyl carbon reported by Martin et al. (Scheme 5). ... 

The synthesis of /8-chloro-a-cyanoenamines from JV-l-(2,2-dichloroalky-lidene)amines has been described/ " and the geminal acylation-alkylation of regiospecifically generated metalloenamines/ and applications to alkaloid synthesis/ have been reported. 

Diazoalkanes react with ethyl fluoroformate [S7j and acyl fluorides [87, 55] to give ethyl ot-fluorocarboxylates and ot-fluoroketones, respectively (equation 22) Table 7 lists examples of hydrofluorination [6. 83, 89] and geminal difluori-nation [90] of aryldiazomethanes... 

As an illustrating example for the application of the Friedel-Crafts acylation in the synthesis of complex molecules, its use in the synthesis of [2.2.2]cyclophane 13 by Cram and Truesdale shall be outlined. The reaction of [2.2]paracyclo-phane 10 with acetyl chloride gives the acetyl-[2.2]paracyclophane 11, which is converted into the pseudo-geminal disubstituted phane 12 by a Blanc reaction, and further to the triple bridge hydrocarbon 13 ... 

Compounds containing geminal carboxyl groups (disubstituted malonic acid derivatives) can also be bisdecarboxylated with lead tetraacetate, gcm-diacetates (acylals) being produced, which are easily hydrolyzable to ketones ... 

Initiator decomposition studies of AIBN in supercritical C02 carried out by DeSimone et al. showed that there is kinetic deviation from the traditionally studied solvent systems.16 These studies indicated a measurable decrease in the thermal decomposition of AIBN in supercritical C02 over decomposition rates measured in benzene. Kirkwood correlation plots indicate that the slower rates in supercritical C02 emanate from the overall lower dielectric constant (e) of C02 relative to that ofbenzene. Similar studies have shown an analogous trend in the decomposition kinetics ofperfluoroalkyl acyl peroxides in liquid and supercritical C02.17 Rate decreases of as much as 30% have been seen compared to decomposition measured in 1,1,2-trichlorotrifluoroethane. These studies also served to show that while initiator decomposition is in general slower in supercritical C02, overall initiation is more efficient. Uv-visual studies incorporating radical scavengers concluded that primary geminate radicals formed during thermal decomposition in supercritical C02 are not hindered to the same extent by cage effects as are those in traditional solvents such as benzene. This effect noted in AIBN decomposition in C02 is ascribed to the substantially lower viscosity of supercritical C02 compared to that ofbenzene.18... 

Acylals (geminal diacetates) are frequently used as protecting groups for aldehydes because of their stability to neutral and basic conditions [8]. In addition, the acylal functionality can be converted into other useful functional groups [9]. For example a novel synthesis of chiral allylic esters has been developed using palladium-catalyzed asymmetric allylic alkylation of gem-diesters [10]. The allylation of... 

Gas electron diffraction (GED) acyl peroxides, 702 peroxynitrates, 743-4 see also Electron diffraction Gas-hqiud chromatography (GLC) hydroperoxide determination, 684-5 ozonide determination, 719 Gas-phase addition, hydroperoxides, 157 Gas-phase epoxidation, alkenes, 58 gauche arrangement, acyclic organic peroxides, 102, 104-5 GED (gas electron diffraction), 743-4 Geminal regioselectivity... 

Chemical shifts and coupling constants of substituted 1,2,3,4-tetra-hydroquinoxalines indicate that the heterocyclic ring in these derivatives is in the half-chair form.263 The variation of the cis vicinal and geminal couplings resulting from acylation on nitrogen indicates that the acylated derivatives have a slightly flattened half-chair conformation.263... 

Alternatively, an anion stabilizing group alpha to the carbonyl group of the cyclo-butanone provides a pathway for cleavage by attack of a nucleophile on the cyclo-butanone carbonyl carbon. C-Acylation creates the familiar 1,3-dicarbonyl system which, by deacylation involving attack at the cyclobutanone carbonyl group, leads to a geminal alkylation as shown in Eq. 115 b 47,79). 

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