Nucleophiles, vinylogous

Nucleophilic attack on ring carbon (Scheme 39) is the most important reaction of these compounds (the electrophile may bond to oxygen either before or after nucleophilic attack). For vinylogous nucleophilic opening by 5n2 attack on ethenyloxiranes see Section 5.5.3.8. 

While the usual eonsequence of hydration of enamines is eleavage to a secondary amine and an aldehyde or ketone, numerous cases of stable carbinolamines are known (102), particularly in examples derived from cyclic enamines. The selective terminal hydration (505) of a cross-conjugated dienamine-vinylogous amide is an interesting example which gives an indication of the increased stabilization of the vinylogous amide as compared to simple enamines, which is also seen in the decreased nucleophilicity of the conjugated amino olefin-carbonyl system. 

The formation of vinylogous amides from primary amines and -dicarbonyl compounds gives rise to hydrolyzable amine derivatives with greatly decreased nucleophilicity of the nitrogen function. Thus these derivatives have found some use as protecting groups in peptide syntheses 617-619). 

In the oxidative Eschenmoser sulfide contraction (Scheme 11), thioamide 59 is oxidized by benzoyl peroxide to give either a symmetrical disulfide or the O-benzoate of the thiolactam-S-oxide. In any event, the once-nucleophilic thioamide sulfur atom is now forced to adopt the role of electrophile a reactivity umpolung has, in effect, been achieved.13 The nucleophilic enamide 65 attacks the sulfur atom leading to the formation of sulfur-bridged intermediate 66. The action of a phosphine or a phosphite thiophile on the putative episulfide then gives vinylogous amidine 67. 

If vinylogous imidazole-A-carboxylates (route A) are treated with nucleophiles such as alkoxides or amines, the corresponding vinylogous carbonic esters or amides are obtained. While reaction of the vinylogous imidazole-TV-carboxylate with a thiol (route A) yields the addition product only, that of the corresponding imidazolium compound (route B) leads to the carbonic thioester in a substitution reaction [3]... 

The 3-methylimidazolium-3-amino-2-propen-l-one compounds can also be considered as vinylogous azolides, as the following reactions with nucleophiles demonstrate ... 

Triisopropylsilyloxyfurans were effective nucleophiles for the vinylogous Mannich addition to iminium ions that were formed by Rh2(cap)4-catalyzed oxidation of N-alkyl groups by THYDRO <06JA5648>. A stereoselective addition of 2-trimethylsilyloxyfurans to aryl aldehydes-derived aldimines employing a chiral phosphine/Ag complex as catalyst was developed <06AG(I)7230>. The prototypical example is shown below. 

Addition of carbon nucleophiles to furfural tosylhydrazone provides 5-substituted 2E,4E-pentadienyls in good yields <00TL2667>. The ab initio calculations at the RHF/3-21G level have been utilized to study the origins of diastereoselectivity of the vinylogous Mannich reaction of 2-methylfuran with pyrrolinium ion . A simple procedure for isomerization of 2-furylcarbinols to cyclopentenones under neutral condition was reported and a new mechanism was proposed <00H(52)185>. 

Having used their catalytic systems with dienolates derived from unsaturated esters, Denmark performed aldol reactions with the dioxanone-derived dienol ether described above in the context of Carreira s and Campagne s vinylogous aldol reactions (Scheme 21). Here, exclusively, the y product was formed with the nucleophile attacking from the Re face. For all three aldehydes, very good yields (83-92%) and selectivities (74-89% ee) were observed with only 0.01-0.05 mol% of the catalyst. 

Chen and co-workers utilized the chiral bifunctional catalysts to directly access vinylogous carbon-carbon bonds via the asymmetric Michael addition of a,a-dicy-ano-olefms to nitro-olefms [102]. The scope of the reaction was explored with a variety of substituted a,a-dicyano-olefins and P-substituted nitro-olefms (Scheme 50). The authors propose the catalysf s tertiary amine functionality depro-tonates the cyano-olefm, activating the nucleophile to add to the -face of the pre-coordinated nitro-olefm. 

Finally, by placing the additional carbonyl in the carboxylic component, a synthesis of pyridinones 131 has been realized [115]. In this case, the nucleophilic carbon is not the one derived from the acid, but the one initially embedded in the starting aldehyde. Moreover, here a vinylogous Knoevenagel is operating, which is clearly favoured over the reaction involving the carbon a to the amide, thanks to the formation of a stable aromatic 6-membered ring. 

Heterocyclic secondary 183-type enamines (exocyclic vinylogous urethanes) show ambident bisnucleophilicity their nucleophilic reaction... 

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