Cyclization Conia-ene

Allenyl ketones can undergo a Conia-ene cyclization, as shown in Eq. 13.56 [65]. Heating ketone 166 at 275 °C for 15 min leads to acetylcyclopentene 168 in 70% yield. Cyclization presumably takes place through a pericyclic mechanism involving enol 221. 

A combination of experimental results and quantum mechanical calculations has contributed to the understanding of the enantioselective Conia-ene cyclization of alkyne-tethered / -ketoesters (144), catalysed by the cinchona-derived urea pre-catalysts (146) and TfOCu, which affords (145) with <93%... 

Two types of carbon nucleophiles are commonly utilized in gold catalysis electron-rich (hetero)arenes [3,6] and 1,3-carbonyl compounds [94—104]. The first will be discussed later. The addition of 1,3-carbonyl compounds to alkynes, known as the Conia-ene cyclization [94—104], takes place via the corresponding enol tautomer or the corresponding silyl enol ether (Scheme 1.4). 

The Conia-ene reaction is a thermal cyclization of an alkyl ketone with an alkyne to give the corresponding a-vinylated ketone.98 The catalytic version of this reaction has been reported to generalize the process to more functionalized substrates.99 The intramolecular carbocupration of alkyne 94 has been investigated under basic conditions in the presence of a catalytic amount of copper iodide (Scheme 28).100 The cyclic product 95 is obtained in high yield. 

The phyllocladane skeleton 131 was constructed efficiently by stereoselective formations of six carbon-carbon bonds and four rings via a one-pot sequence of cyclizations the ene type, [2+2+2], and [4+2] cycloadditions. In this synthesis, the Conia ene reaction of 127 takes place under mild conditions to generate 128, and the cyclotrimerization of its diyne with 118 gives 129. These two reactions are catalysed by CpCo(CO)2. Finally, ring-opening to give 130 and intramolecular Diels-Alder reaction in the presence of DPPE produced the phyllocladane skeleton 131 in a total yield of 42% [55]. 

The Conia-ene reaction was brought to the held of gold catalysis by Toste et al.29 It provided very mild conditions for this cyclization to a functionalized hve-membered ring (Scheme 12.14). 

The thermal cyclization of ketones onto alkynes, the Conia-ene reaction, can proceed thermally but only at inconveniently high temperatures.39 Transition metals can catalyse it at lower temperatures but they require enolate generation, strong acid or photochemical activation. In the presence of phosphaneAu1 complexes, however, the reaction proceeds at ambient temperature under neutral conditions. For example, the following ketoester was converted into the cyclic product in 94% yield in 15 min in the... 

Ene Reactions.—Conia, who has done so much to demonstrate the synthetic utility and versatility of unsaturated carbonyl compound cyclizations, as exemplified by the prototype conversion of(271) into (272), has reviewed recent developments which includes applications to bridged-ring compound synthesis. The same group have reported on the double thermal cyclization of 3,3-dibutynylcyclopentanone (273) to give the [3,3,3]propellenes (274 60%) and (275 5%), and the monocyclization product (276 10%). Since (274) is stable under the reaction conditions, (275) is presumably formed from (276) by isomerization prior to a second ene cyclization step. 

The intramolecular ene reaction with an enol as the ene component is known as the Conia reaction. Very high temperatures are normally required and more efficient is the use of a cobalt catalyst or the use of a zinc enolate. Thus, formation of the zinc enolate 257 from the ester 256 promoted cyclization at room temperature to give, after quenching the intermediate organozinc species with a proton, the cis pyrrolidine 258 (3.164). 

The possibility of developing activated ene donors is discussed above. As active donors are coupled with active acceptors, it may be possible to develop routes to heretofore relatively inaccessible ring systems and substitution patterns. In particular, one or more of the interacting carbon atoms could be replaced with a heteroatom. Several such systems, as exemplified by the acyl nitroso acceptors of Keck [26], the Lewis acid-mediated carbonyl acceptors developed by Snider [27], and the enol donor cyclizations of Conia [28], have already been investigated. 

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