Cycloaddition with enones

Cycloaddition with enone reactants has been studied using cyclopentenone or cyclohexenone derivatives in order to avoid side reactions resulting from cis-trans isomerization of the alkene. In the case of cyclopentenone or cyclohexenone, regioselectivity of cycloaddition is influenced by the substituents at the C-3 position as well as whether or not the 4-position is a heteratom. 

TMM cycloadditions to cyclic and conjugated ketones have also been reported (Scheme 2.22) [31]. The steric nature of the substrate does play a critical role in determining product formation. Thus the cyclic ketone (73) produced 55% yield of the tetrahydrofuran, but no cycloadduct could be obtained from the cyclic ketone (74). The enone (75) gave only carbonyl cycloaddition, whereas enone (76) yielded only olefin adduct. Interestingly, both modes of cycloaddition were observed with the enone (77). The ynone (78) also cycloadds exclusively at the carbonyl function [34]. 

Cyclopropyl ketones 32 and cyclopropyl imines 33 can also undergo [3+2] cycloaddition reactions with enones 34 in presence of NHC-Ni complexes to afford the corresponding cyclopentane compounds 35 (Scheme 5.9) [11]. The catalytic system is prepared in situ from the use of [Ni(COD),], SIPr HCl salt and KOBu, the reaction also required the use of Ti(O Bu) as an additive to improve yields and increase reactions rates. In most of the cases, th products 35 were obtained in good to excellent diastereoselectivities. 

Scheme 5.9 NHC-Ni catalysed [3-I-2] cycloaddition reaction of cyclopropyl ketones or cyclopropyl imines with enones...

Although the enones (15) underwent [2 + 2]cycloaddition with (16) with complete regiospecificity, the reaction between cyclohexenone (19) and (16) yielded the isomeric inseparable (20) and (21) in 3 1 ratio. Compound (20) and (21), upon... 

Given a typical diene, an increased reactivity is expected of the reaction with en-hanciftg polarity alternation of the dienophile. This is easily appreciated in view of an ionic reaction being more exothermic. Thus, acryloxyboranes [172] undergo cycloaddition with cyclopentadiene even at —78 °C. The same principle underlies dienophile activation by replacing an enone with an alkoxyallyl cation [173] or allylidene-metalcarbonyl [174],... 

Thioenol ethers can undergo cycloadditions with a,/ -unsaturated ketones in the presence of aluminum trichloride to give cyclobutyl ketones under mild conditions.13 In contrast, thermal [2 + 2] cycloadditions to enones have never been observed. 

In cycloadditions of enones to alkenes novel strategies have been adopted for ring expansion of the cycloadducts, either by the choice of appropriate alkenes, e.g. 2-(trimethylsiloxy)buta-1,3-diene,70 vmv-2-trimethylsiloxybuten-2-oales71 or 3,3-dimethylcyclopropene,72 or by using 3-oxo-l-cyeloalkene-l-carboxylates as enones.73 Asymmetric [2 + 2] photocycloaddition of cyclopent-2-enone to a (+ )-dihydrofuran acetonide constitutes the cornerstone of the synthetic strategy in the first total synthesis of the novel antitumor metabolite ( )-echinosporin.74 The cycloaddition product 25 from treatment of 2-(2-carbomethoxyethyl)-2-cyclopentenone (24) with ethene has been used as a precursor for the preparation of tricyclo[4.2.0.01,4]octane.75... 

The reaction between vinyl ethers and unsaturated carbonyl compounds, which provides a powerful synthetic route to dihydropyrans, has been adapted to the synthesis of pyran-2-ones (72CC863). 2-Chloro-1,1 -dimethoxyethylene, which is a protected form of chloroketene, undergoes cycloaddition with a number of enones to give the cis or trans isomers of 3-chloro-3,4-dihydro-2,2-dimethoxypyrans (338) and (339) or a mixture of both. Although... 

Cycloadditions of Enones and Pyridinones. When the carbonyl group is conjugated to a C=C double bond, cycloaddition takes place at that double bond and a new ketone is formed. These reactions are fairly general with enones and their derivatives, as illustrated in Figure 4.54. The cyclobutane products are often useful synthetic intermediates. 

As early as 1964, Corey had suggested the intermediacy of an oriented pi complex in the cycloaddition of enones (43) and soon thereafter Hammond and coworkers, on the basis of arene fluorescence quenching by dienes, suggested the possible involvement of a polar excited state complex with substantial charge transfer character (44). Since then the possibility of cycloadditions occurring through the intervention of exciplex or excimer intermediates per se or as precursors for radical ions pairs, eq. 12,... 

The intramolecular 2 + 2-photo-cycloadditions of optically active allenesilanes (5) with enones and enoates produce silyl-substituted exo-methylenecyclobutanes (6) in high enantiometric excess. Photo-desilation leads to the parent unsaturated exo-methylenecyclobutanes (7) (Scheme 3).19 The cycloaddition of naphthoquinone to allyltrimethylsilane in the presence of Me2 A1C1 yields the expected 2 + 2-cycloadduct that slowly rearranges to the 2 + 3-adduct.20 hi the presence of bases, Cephalosporin triflates (8) undergo 2 + 2- and 4 + 2-cycloaddition with alkenes, alkynes, and dienes via an intermediate six-membered cyclic allene (9) (Scheme 4).21... 

In another attempt, we reached the tetracyclic structure 42 via two consecutive [4 + 2] cycloaddition reactions. Reaction of 3-cyano-4-benzopyrone 31 with Danishefsky s diene 38 in toluene at 300 °C for 96 h provided the desired cycloadduct 39 in 80% yield with an endo exo ratio of 1 2 [Scheme 8]. Hydrolysis of the silyl enol ether in 39 using TMSBr in CH3CN at room temperature proved to be feasible but slow, and afforded the enone 40 in 90% yield. Reaction of diene 41 with enone 40 in the presence of 2.5 equiv of BF3-Et20 yielded tetracycle 42 in 25% yield with an endo exo ratio of 1 1 after 120 h at room temperature.49... 

Diels-AIder reaction with Lewis acid (MgBr2 or C2H5 A1C12) proceeds stereospecifically to give cra/o-adducts in which the phenylthio function is oriented ortho to the carbonyl group (7, 75-76). The related dienes 2 and 3 undergo cycloaddition with similar stereo- and regiospecificity. 

Most cyclobutanes offer a choice between two 2 + 2 disconnections and the choice can often be made by considering the availability of the starting materials. We already know from 11 that compounds like this can be made by irradiation of ethylene with enones, here 15, so we shall focus on the alternative 16b. The starting material for an intramolecular photo-cycloaddition would be dienone 17. It was decided to make this by oxidation of 18 because this alcohol was easy to make.7... 

Cycloadditions.1 Acyclic enones do not usually undergo photochemical l2+2]cycloaddition with alkenes, but this Ti(lV) Lewis acid does promote this cycloaddition in the case of methoxymethyl vinyl ketone and, to a less extent, of methyl vinyl ketone. Usually 2 equiv. of 1 or of TiCl2(0-/-Pr)2 is required. 

Wilson, J.E. and Fu, G.C. (2006) Synthesis of functionalized cyclopentenes through catalytic asymmetric [3 + 2] cycloadditions of allenes with enones. Angewandte Chemie, International Edition, 45, 1426-1429. 

The reaction of homochiral allylsilanes with a-enones and a-enals is very valuable for the asymmetric synthesis of multisubstituted cyclopentanes (Equation (40)).161,162 The [3 + 2]-cycloaddition of allylsilanes is applicable to />-quinones163 and />-quinoneimines.164 3-Butyn-2-one undergoes a double cycloaddition with an excess amount of allyltriisopropylsilane to give a bicyclo[3.3.0]octane in good yield (Equation (41)).165... 

These silanes undergo regiospecific [3 + 2] cycloaddition with a,(3-enones in the presence of TiCU to form cyclopentenes stereoselectively (10, 429). ... 

The synthesis and relative stability of 3,5-diacyl-4,5-dihydro-l//-pyrazoles prepared by dipolar cycloaddition of enones and a-diazoketones has been published <2004JOC9085>. 3-Acyl-4-aryl-2-pyrazolines have been synthesized by the reaction of a,/3-unsaturated ketones with diazomethane <1996IJB1091>. Ethyl diazoacetate added to 1,3-diarylpropenones in a regioselective fashion to give the intermediate 4,5-dihydto-3//-pyrazole derivative 1,3-hydride shift in the latter led to the formation of the isomeric ethyl 4-aryl-5-aroyl-4,5-dihydro-l//-pyrazole-3-carboxylate and ethyl 4-aryl-3-aroyl-4,5-dihydro-l/7-pyrazole-5-carboxylate in a ratio of 5 1 <2001RJ01517>. 1,3-Dipolar cycloaddition of 2-diazopropane with diarylideneacetones afforded diastereomeric bis-A -pyrazolines <1999T449>. 

High regioselectivity is found in the photochemical addition of allene to the enones (98). With enone (98a) cycloaddition affords (99) while (98b) yields the adduct (100). This compound was used for subsequent reactions in syntheses of taxane-like molecules. 

In 1996, Ciufoiini and Roschanger reported a total synthesis of phenanthroindolizidine alkaloids (tylophorine and antofine) from the sterically congested 2-substituted 4,5-diarylpyridine 61, which was prepared by a modified Knoevenagel-Stobbe synthesis [61]. Scheme (6) outlines the steps in their approach. Central to the success of this effort was the ability of a-dicarbonyl enone 58 to combine in a formal [4+2]-cycloaddition with the sterically demanding vinyl ether 56, The resultant pyran 59 was treated with DIBAL and protected with benzyl chloride giving 60, which was then treated with hydroxylamine hydrochloride to give diarylpyridine 61, After a two-step conversion of 61 to 63, a cyano... 

---