Addition elimination enol chloride

Kinetics of the reaction of p-nitrochlorobenzene with the sodium enolate of ethyl cyanoacetate are consistent with this mechanism. Also, radical scavengers have no effect on the reaction, contrary to what would be expected for a chain mechanism in which aryl radicals would need to encounter the enolate in a propagation step. The reactant, /i-nitrophenyl chloride, however, is one which might also react by the addition-elimination mechanism, and the postulated mechanism is essentially the stepwise electron-transfer version of this mechanism. The issue then becomes the question of whether the postulated radical pair is a distinct intermediate. 

The Grohe-Heitzer sequence (Scheme 4.2) begins with acylation of malonate derivative 37 with benzoyl chloride 36 to give malonate 38 (Mitscher, 2005). Condensation of the malonate with an ortho-ester in the presence of a dehydrating agent such as acetic anhydride affords enol ether 39. The enol ether then undergoes an addition-elimination... 

Oppolzer et al. (321) applied his own sultam as the auxiliary for a cychc nitrone in the synthesis of (—)-allosedamine (Scheme 12.60). The enantiomerically pure nitrone 209 was synthesized from 208 by base treatment, attack of the enolate on 1-chloro-l-nitrosocyclohexane at the nitrogen atom, and subsequent elimination of chloride. Subsequent addition of aqueous HCl gave the cyclic nitrone 209. The nitrone participated in a 1,3-dipolar cycloaddition with styrene, proceeding with complete exo-specificity. The product, 210, was obtained with a de of 93%. Two further reaction steps yield the piperidine alkaloid ( )-aUosedamine 211 in an overall yield of 21%. 

A neurokinin inhibitor whose strueture differs markedly from aprepitant (200) incorporates a substituted tetrazole ring. The synthesis of the tetrazole-containing moiety of vofopitant (241) start by acylation of substituted aniline 231 with trifluoroaeetyl ehloride to afford the amide (232). Reaction of that under Mitsonobu eonditions leads to the enol chloride (233). Treatment of 233 with sodium azide probablty starts with addition-elimination of azide ion this undergoes internal 1,3-cycloaddition to form the tetrazole ring. Catalytie hydrogenation then removes the benzyl... 

The other is a two-step, elimination-addition mechanism. In the elimination step, / elimination occurs by an E2 mechanism to give a ketene, a very reactive compound that is not usually isolable. In the addition step, the alkoxide adds to the electrophilic carbonyl C of the ketene to give the enolate of an ester. Acyl chlorides lacking a-hydrogens (t-BuCOCl, ArCOCl), of course, can react only by the addition-elimination mechanism. 

Attack by the enol at phosphorus gives an activated enol, which may further react by a nucleophilic addition-elimination process with chloride, along with formation of a P=0 containing product, which provides the driving force for the reaction. 

An important modification of the initial protocol has been introduced by Larock ef al. to afford indanones. The saturated ring results from the termination of the process by protonolysis of palladium enolate, which is likely to be generated from reversible palladium hydride elimination-addition. Proton source required for protonolysis hypothetically comes from adventitious water coming with hygroscopic chloride or solvent (Scheme 13). ... 

The first starting material for building benzodiazepines was prepared inadvertently in a synthesis aimed at the benzodiazoxepine (6-1). The oxime acetamide (6-2) from 2-aminobenzophenone was thus treated with hydrogen chloride in the expectation that the new heterocycle would form by the elimination of water between the oxime and the enol form of the amide. The product mrned out in fact to be the quinazoline A-oxide (6-3), the product from the addition of the nucleophilic oxime nitrogen to the amide carbonyl group. 

In another simple procedure, deprotonation of methoxy bis(trimethylsilyl)methane with butyl lithium and addition of the resulting anion to aldehydes induces Peterson elimination (Scheme 27). The product methyl enol ethers could be hydrolysed to the parent acyl silanes with hydrochloric acid-THF or could be treated with electrophiles such as M-halosuccinimides to give a-haloacyl silanes105. Alternatively, treatment with phenyl selenenyl chloride, oxidation at selenium and selenoxide elimination afforded a,/3-unsaturated acyl silanes. 

A number of a,/J-unsaUiraled acyl silanes have been prepared from silyl enol ethers of acyl silanes (Scheme 41)129. Addition of phenyl sulphenyl chloride to the silyl enol ether with subsequent elimination of chlorotrimethylsilane gives the a-(phenylthio)acyl silane. Oxidation to the sulphoxide followed by in situ elimination of benzenesulphenic... 

The active-methyne compounds, which derive from the acylation of the enolates of active-methylene compounds with carboxylic acid chlorides, eliminate the extra acceptor(s) in an additional step or immediately in situ. The defunctionalizations involved include one or two decaboxylations depending on the nature of the reactants and subsequent processing steps (Figures 13.66 and 13.67)... 

Complex 1 also catalyzes the regioselective radical addition of perhalogeno-ethanes to silyl enol ethers. The primary addition-desilylation products undergo the facile /1-elimination of a chloride to afford a,/3-unsaturated ketones [26, 27]. For example, CF2C1CC13 adds to the trimethylsilyl enol ether of acetophenone to yield /i-chloro-/i-(chlorodifluoromethyl)-a,/ -acetophenone in 80% yield (Eq. 9). 

---