Intramolecular conjugate displacement

Dimethylsulfonium methylide is both more reactive and less stable than dimethylsulfoxonium methylide, so it is generated and used at a lower temperature. A sharp distinction between the two ylides emerges in their reactions with a, ( -unsaturated carbonyl compounds. Dimethylsulfonium methylide yields epoxides, whereas dimethylsulfoxonium methylide reacts by conjugate addition and gives cyclopropanes (compare Entries 5 and 6 in Scheme 2.21). It appears that the reason for the difference lies in the relative rates of the two reactions available to the betaine intermediate (a) reversal to starting materials, or (b) intramolecular nucleophilic displacement.284 Presumably both reagents react most rapidly at the carbonyl group. In the case of dimethylsulfonium methylide the intramolecular displacement step is faster than the reverse of the addition, and epoxide formation takes place. 

There are two general routes toward the synthesis of azinomycin. Both approaches generally prepare the top half of the molecule and then generate the reactive aziridine ring late in the synthesis. The two general approaches to aziridine formation are the formation of the exocyclic C-N bond through a nucleophilic displacement or an intramolecular conjugate addition/elimination of an intact monocyclic aziridine. 

A related approach for the synthesis of spirocyclopenteneoxindoles was developed by Barbas and coworkers. Chiral diphosphines catalyzed the [3+2] cycloaddition between the A-protected methyleneindolin-2-ones 17b and the Morita-Baylis-Hillman (MBH) carbonates 37 [18]. This reaction was initiated by the displacement of the carbonate moiety by the phosphine VI, an addition-elimination mechanism, which was followed by the deprotonation to afford ylide 39. A regioselective nucleophilic addition on 17 by 39, followed by an intramolecular conjugate addition, afforded intermediate 40 that, after elimination of PR3, delivered the corresponding spirocycle 41 (Scheme 10.11). 

Base-promoted cyclization of vicinal halohydrins (Section 16.10) This reaction is an intramolecular version of the Williamson ether synthesis. The alcohol function of a vicinal halohydrin is converted to its conjugate base, which then displaces halide from the adjacent carbon to give an epoxide. 

Cory and Renneboog53 have devised an efficient bicycloannulation for the synthesis of tricyclo[3.2.1.02,7]octane-6-one (66) as shown in equation 63. The method involves three steps (1) the enolate undergoes an initial conjugate addition to phenyl vinyl sulfone, (2) the resulting sulfone-stabilized carbanion undergoes an intramolecular Michael addition to the enone, and (3) the resulting enolate displaces phenylsulfinyl moiety from the tricyclooctanone. The amount of HMPA (3 mol equivalents) is critical for effective cyclization of the enolate. 

Diketones usually exist as mixtures of tautomeric keto and enol forms. The enolic form does not show the normal absorption of conjugated ketones. Instead, a broad band appears in the 1640-1580 cm-1 region, many times more intense than normal carbonyl absorption. The intense and displaced absorption results from intramolecular hydrogen bonding, the bonded structure being stabilized by resonance. 

Bicyckmnneiation. The first step of a new method for this reaction involves conjugate addition of a cyclic dienolate to a nitro olefin followed by an intramolecular displacement with loss of the nitro group. An example is the reaction of the a -enolale of isophorone (1) with 1-nitropropene. When refluxed with HMPT the initial adduct (2), which can be isolated, is converted into the tricyclooctanones 3 uml 4 iu 63 yield.4... 

Scheme 18). The formation can be explained by the initial conjugate umpolung of the aldehyde and subsequent 1,4-addition to the unsaturated ketone. After proton transfer, an intramolecular aldol-type addition results in the formation of the aforementioned zwitterions. Nucleophilic displacement of the imidazolium moiety by the alkoxide provides the p-laclonc, which exhibits increased strain, since it is annulated to a cyclopentane ring. Consequently, the P-lactone breaks apart and liberates CO2 and the observed cyclopentene products (Scheme 19). 

When the enones 1 were treated with the ai-haloalkanols 2 and base, the deformylated cfv-prod-ucts rac-3 were obtained exclusively13. Clearly this reaction is initiated by conjugate addition of the O-nucleophile. The diastereoselective step, however, is the subsequent intramolecular displacement of halide by the intermediate enolate anion. 

Exceptionally clean cyclization can be accomplished by utilizing conjugated enones as precursors for the Barbier reaction (equation 43). High diastereoselectivity is achieved in these reactions, and under the mild conditions required for cyclization the TMS ether protecting group remains intact. It is also interesting that a neopentyl halide is effective in the cyclization. This result would appear to exclude an 5N2-type displacement of an organic halide by a samarium ketyl as a possible mechanism for the Smh-promoted intramolecular Barbier reaction. 

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