Unsaturated carbonyl compounds 1.4- Diene-3-ones

Besides direct nucleophilic attack onto the acceptor group, an activated diene may also undergo 1,4- or 1,6-addition in the latter case, capture of the ambident enolate with a soft electrophile can take place at two different positions. Hence, the nucleophilic addition can result in the formation of three regioisomeric alkenes, which may in addition be formed as E/Z isomers. Moreover, depending on the nature of nucleophile and electrophile, the addition products may contain one or two stereogenic centers, and, as a further complication, basic conditions may give rise to the isomerization of the initially formed 8,y-unsaturated carbonyl compounds (and other acceptor-substituted alkenes of this type) to the thermodynamically more stable conjugated isomer (Eq. 4.1). 

Cyclobutane formation via light-induced [2 + 2] cycloaddition is probably one of the best studied photochemical reactions and has been reviewed thoroughly up to 1972 (Houben-Weyl, Vols. 4/5 a and 4/5 b). The most important types of C —C double-bond chromophores undergoing such reactions arc alkenes, 1,3-dienes, styrenes, stilbenes, arenes, hetarenes, cycloalk-2-enones, cyclohexa-2,4(and 2,5)-dienones, 1,4-benzoquinones, and heteroanalogs of these cyclic unsaturated carbonyl compounds. For p notocyciodimerizations see Houben-Weyl, Vol. 4/5 a, p 278 and for mixed [2 + 2] photocycloadditions of these same chromophores to alkenes see Section 1.3.2.3. 

The 4-vinyloxetan-2-ones generated in a Pd-catalysed [2+2] cycloaddition between ketene and a,P-unsaturated carbonyl compounds undergo a spontaneous allylic rearrangment. A zwitterionic intermediate is proposed that cyclises to a 3,6-dihydro-2//-pyran-2-one, but which may alternatively decarboxylate to a diene <02T5215>. 

Addition of an unsymmetrical diene to an unsymmetrical dienophile can take place in two ways to give two structurally isomeric products. It is found in practice, however, that formation of one of the regioisomers is strongly favoured and that this can be predicted prior to reaction. Obviously, this is crucial if the Diels-Alder reaction is to be used successfully in synthesis. Cycloaddition of 1 -substituted butadienes with dienophiles such as a,p-unsaturated carbonyl compounds gives rise to... 

The case of a,j8-unsaturated carbonyl compounds is analogous to that of 1,3-dienes in that stereoelectronic factors favor coplanarity of the C=C—C=0 system. The rotamers that are important are the s-trans and s-cis conformations. Microwave data indicate that the s-trans form is the only conformation present in detectable amounts in acrolein (2-propen-l-one). The equilibrium distribution of s-trans and s-cis conformations of -unsaturated ketones depends on the extent of van der Waals interaction between substituents. Methyl vinyl ketone has no unfavorable van der Waals repulsions between substituents and exists predominantly as the s-trans conformer ... 

The inverse procedure, double bond tritiation followed by re-oxidation, allows for the tritium labeling of a,/8-unsaturated carbonyl compounds (Figure 10.7). Applied to the complex steroid 22 it provided [ H]25, in which 95% of the tritium was located at C2. If most tritium in the intermediate 34 had been on the a-face and equally distributed between Cl and C2, in analogy with the preparation of [ C]24 under very similar conditions, then the benzeneselenic anhydride-mediated dehydrogenation must have constituted a net la,2)3 elimination. This selectivity is consistent with the DDQ dehydrogenation of [la,2a- H]androst-4-ene-3,17-dione (36) to give [2- H]androsta-l,4-dien-3,17-dione (2Z) with little tritium at Cl, and DDQ dehydrogenation of [l)3,2)3- H]testosterone 1381 to provide mainly 17)3-hydroxy[l- H]androsta-l,4-dien-3-one (39) . 

One of the limitations of the photocycloaddition reaction is that the unsaturated system may itself act as a quencher. Conjugated dienes fall within this category since they quench the n,ir triplet of some carbonyl compounds. For the photoreduction of benzophenone in benzhydrol, the ratio, kqlka, for m-piperylene is 750 (Table II), which indicates that this diene is indeed an efficient quencher for the reaction. 

An alternative procedure is to convert the carbonyl compound into the toluene-p-sulphonylhydrazone,12 followed by reduction with either sodium borohydride in acetic acid,13 or with catecholborane, followed by decomposition of the intermediate with sodium acetate or tetrabutylammonium acetate.14 The former method is illustrated by the conversion of undecan-6-one into undecane (Expt 5.6), and the latter by the conversion of acetophenone into ethylbenzene (Expt 6.4, Method B). A feature of these methods is that with a, / -unsaturated ketones, migration of the carbon-carbon multiple bond occurs thus the tosylhydrazone of isophorone gives 3,3,5-trimethylcyclohex-l-ene, and the tosylhydrazone of oct-3-yn-2-one gives octa-2,3-diene. 

R)- and (S)-f-Butyl-5-methylene-l,3-dioxolan-4-one, a Chiral a-Alkoxy Acrylate. It is also possible to introduce an ex-ocyclic double bond onto the dioxolanone ring, as in compounds (9)-(ll), derived from lactic and malic - acids. These a,3-unsaturated carbonyl derivatives are acceptors for radical additions and undergo cycloadditions with dienes and heterodienes. The Diels-Alder adduct (12) of ent-(9) with cyclopentadiene is formed with exo selectivity (96 4) and serves as aprecursor to norbomenone (13). Cycloadduct (14), obtained from methylenedioxolanone (9) and an open-chain triene, is also the result of an exo addition and is used in tetronolide synthesis. ... 

The results of the reductions of some steroidal a,)3-unsaturated ketones have been summarized by Brown. " The carbonyl group is usually reduced to the hydrocarbon, but the behavior of the double bond depends on the structure of the compound undergoing the reduction. Cholest-4-en-3-one gives chol-est-4-ene. Addition of aluminum chloride to a solution of a 4-ene-3,6-dione followed by treatment with LiAIH4 gives the 4-ene-6-one. Steroid 4,6-dien-3-ones yield mixtures of dienes. When the ketone and double bond are in different rings the results become even more complex dienes as well as mono-enes are obtained. 

These metal-alkynyl complexes can be protonated to afford the free alkynes and parent cobalt hydroxo complex (comparable reactivity to their alkyl and aryl congeners), but have proven inert toward oxygenation and carbonylation. They are also thermally stable up to 100 °C. Attempts to explore the reactions of these compounds with unsaturated hydrocarbons were typically fruitless. The one exception is the reaction between 53 and its parent alkyne (HC = C02Me, Scheme 6), which under benzene reflux effects catalytic, stereospecific, linear trimerisation of the alkyne to afford ( , )-buta-l,3-dien-5-yne. The reaction was, however, slow (4.5 turnovers in 20 h) and suffered from catalytic deactivation due to hydrolysis of 53, which subsequently reacted with adventitious CO2 to irreversibly form an inert /x-carbonato complex. The catalytic cycle was concluded to involve initially a double coordination-insertion of the C = C bond of methylpropiolate into the Co-Caikyne linkage. Subsequent hydrolysis of the Co-C bond by a third equivalent of HC = CC02Me would then afford the observed product and regenerate 53. However, a definitive explanation for the stereospecificity of the process was not established. 

---