Conjugate addition vinylogous

Utilization of a vinylogous enamine generated via 1,6-selective addition to a,p,Y,6-unsaturated iminium intermediate could potentially provide an intriguing synthetic handle for achieving greater molecular complexity. Experimental demonstration of the feasibility of this approach was provided in the development of a 1,6-selective conjugate addition/vinylogous aldol sequence catalyzed by the... 

Entries 10 to 12 illustrate the use of organocopper conjugate addition in the synthesis of relatively complex molecules. The installation of a f-butyl group adjacent to a quaternary carbon in Entry 10 requires somewhat forcing conditions, but proceeds Transition Metals in ooc yie - I 1 Entry 11, the addition is to a vinylogous ester, illustrating the ability... 

The principle of vinylogy can also be applied to search for other C H acidic compounds as suitable candidates to undergo conjugate addition under iminium activation. This is the case of the vinylogous Michael addition of a,a-dicyanoolefins to a,p-unsaturated aldehydes catalyzed by diphenylprolinol... 

Styrylisoxazoles. On the basis of their previous achievements using styryhsoxazoles as vinylogous electrophiles in the Michael addition with a variety of soft nucleophUes, Bernardi and Adamo [137] fulfilled the successful application of styrylisoxazoles 138 in the asymmetric vinylogous conjugate addition with... 

Formal a-diarylmethylation of malonates was achieved through the development of a 1,6-selective conjugate addition-aromatization sequence with para-quinone methides as vinylogous electrophiles (Scheme 4) [8]. The driving force toward aromatization would make nucleophilic addition to the 8-position more thermodynamically favorable than addition to the p-position. Under solid-liquid biphasic conditions, the A-spiro chiral ammonium salt 5 appeared to be the most active and selective promoter. The electronic character of the aryl ester substituents on the malonate was linked to the stereochemical outcome, and introduction of a para-halophenyl group led to a significant decrease in the enantioselectivity. Based... 

In contrast to the extensive use of nitroolefins in asymmetric Michael additions [10], the vinylogous analogues, nitrodienes and nitroenynes, are less frequently utilized in the conjugate addition of enolate equivalents, despite the significant synthetic utility of the resulting products which possess carbonyl, nitro, and olefin functionalities. Likewise, studies on the hetero-Michael reaction with these acceptors have been very limited, possibly because of apprehension of the site-selectivity issue [11]. 

Scheme 33 Conjugate addition of alkylidene malononitriles as vinylogous nucleophiles...

The utility of the alkylidene oxindole-derived vinylogous enolates was demonstrated in the y-selective asymmetric conjugate addition to nitroolefins (Scheme 38) [67, 68]. Dihydroquinine-derived thiourea 10 earned distinctirm as the most effective catalyst in terms of catalytic efficiency and stereocontroUing ability. The tertiary amine and the thiourea functionalities both appeared to be essential for ensuring catalytic activity. It should be noted that not only perfect y-selectivity but also very high /Z-selectivity were observed under the optimal conditions. A wide variety of nitroolefins and substituted alkylidene oxindoles were amenable to this protocol. 

Friedel-Crafts-type vinylogous conjugate addition of 2-vinyl pyrroles to enals was achieved site-selectively with the use of diphenylprolinol trimethylsilyl ether 14 as an iminium-enaniine activation catalyst (Scheme 41) [71]. Stepwise, formal [2-1-2] cycloaddition would be a plausible outcome of the reaction for constructing stereochemically enriched cyclobutanes. The polarity of the solvent had a critical impact on the catalytic efficiency. Trace amounts or none of the desired product was formed when less polar toluene or dichloromethane was used. Increasing the polarity of the solvent led to enhancement of the turnover frequency of 14 the polar protic solvent, ethanol, was optimal. 

In 2007, the Jorgensen group reported a highly enantioselective procedure for the conjugate addition of oximes to a,p-unsaturated aldehydes in the presence of a chiral amine catalyst (296). This protocol was later expanded to the one-pot synthesis of optically active p-diols by carrying out a vinylogous addition of oxime 317 to different a,p-unsaturated aldehydes in the presence of catalyst 276 followed by a direct reduction of the primary addition product with LiAlHj (297). 

Vedejs has reported an oxaza-Claisen rearrangement to construct the pyrrole derivative 38. In presence of ethyl propiolate, the vinylogous hydroximic acid 35 imdergoes a conjugate addition followed by sigmatropic rearrangement to produce the aldehyde 37. Cyclization and dehydration resulted 38. ... 

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