Conia-ene

Claisen or Cope rearrangement Ester cracking Conia ene reaction... 

Malacria and coworkers [274] used an intermolecular trimerization of alkynes to gain efficient access to the skeleton of the phyllocladane family. Thus, the Co-cata-lyzed reaction of the polyunsaturated precursor 6/4-4 gave 6/4-5 in 42% yield. Here, six new carbon-carbon bonds and four stereogenic centers are formed. The first step is formation of the cyclopentane derivative 6/4-6 by a Co-catalyzed Conia-ene-type reaction [275] which, on addition o f his( Iri me ill y I si ly 1) e thy ne (btmse), led to the benzocyclobutenes 6/4-7 (Scheme 6/4.2). The reaction is terminated by the addition of dppe and heating to reflux in decane to give the desired products 6/4-5 by an electrocyclic ring opening, followed by [4+2] cycloaddition. 

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. 

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. 

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). 

Another version of the Conia-ene reaction is the focus of this research. Here the reaction of y-alkynic (3-ketoesters was tested.48 The screening resulted in a copper / silver cocatalysis system. It remains unclear why the authors did not at least run some reactions with gold catalysts, too, especially since they even cite the work on the gold-catalyzed Conia-ene reaction in the introduction (Section 12.1). 

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... 

Scheme 26 Access to the phyllocladane diterpene skeleton through the cascade Conia-ene/[2 + 2 + 2]/[4 + 2] reactions...

It is noteworthy that the methylenecyclopentane 54 was generated in situ via a cobalt-catalyzed Conia-ene type reaction. By a subtle change in the position of the /J-kclocslcr substituent relative to the tether, the sequence could be reversed and allow the formation of the basic skeleton of the kaurane family [50]. 

Enophiles may include carbonyls, thiocarbonyls, imines, alkenes and alkynes. When the carbonyl is an enophile, the reaction is called a carbonyl ene reaction. The enol form of an unsaturated ketone may serve as an ene in an intermolecular ene reaction known as the Conia-ene reaction. Ene reactions proceed best when the enophilic double bond is electron deficient. Hydrogen is the most common atom transferred in an ene reaction. Other atoms or groups may, however, participate in ene-like transformations. 

Readily available homopropargyl alcohols and diazo dicarbonyl compounds react in a novel formal [4 + 1]-cycloaddition to form various substituted tetrahydrofirrans with E-selectivity exclusively, involving a tandem O—H insertion/Conia-ene cychzation sequence through Rh(II)/Zn(II) cooperative catalysis (140L1004). 

In the Conia-ene reaction, a carbonyl compound enolizes and then undergoes an intramolecular ene reaction. The enol fragment serves as the ene component of the reaction, while the olefin fragment serves as the enophile. An example is the reaction of 8-methyl-7-nonen-2-one (92), which yields 2-isopropylcyclopentyl methyl ketone (93, equation 11.41). ... 

The Conia-ene reaction of P-ketoesters bearing a pendant triple bond involves the cycloisomerization of an enyne formed by enolization. This transformation is efficiently catalyzed by cationic gold(I) complexes and afforded cyclopentane derivatives with excellent yields and moderate to good diastereoselectivities (Scheme 4-40). Acetylenic silyl enol ethers or imines react in an analogous manner. By this method, iodoalkynes were converted into iodocyclopentenes, which are highly useful in natural product synthesis. 

The Conia-Ene reaction is an intramolecular ene reaction of unsaturated ketones, in which the carbonyl functionality serves as the ene component, via its tautomer, and olefinic moiety serves as the enophile. Some of the important examples are summarized in Scheme 6.13. 

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