Addition of Enones

The ease of the photoreaction of with electron-rich organic molecules has been 

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Under thermodynamically controlled conditions, using triethylamine as base for the addition of enones to 5 and sodium methoxide in methanol as base for the addition of a,/ -unsaturated esters, the diastereomeric ratios of 6 range from 95 5 to 97 3. The excellent diasteroselectivities are retained in the Michael addition of 5 to -substituted enones and esters, however, modest synjami selectivities are found212,213. 

Further work by the Ye group has shown that NHCs derived from pre-catalyst 215 can also promote the asymmetric dimerisation of alkylarylketenes 193 to generate alkylidene P-lactones 216 in good diastereo- and enantio-selectivity [83], The asymmetric [4+2] addition of enones and alkylarylketenes to generate 8-lactones 218 in high ee has also been accomplished [84], as has the asymmetric esterification of alkylarylketenes to give esters 217 using benzhydrol, which is assumed to proceed via a Lewis-base mediated mechanism (Scheme 12.46) [85]. 

The mechanism of [3 + 2] reductive cycloadditions clearly is more complex than other aldehyde/alkyne couplings since additional bonds are formed in the process. The catalytic reductive [3 + 2] cycloaddition process likely proceeds via the intermediacy of metallacycle 29, followed by enolate protonation to afford vinyl nickel species 30, alkenyl addition to the aldehyde to afford nickel alkoxide 31, and reduction of the Ni(II) alkoxide 31 back to the catalytically active Ni(0) species by Et3B (Scheme 23). In an intramolecular case, metallacycle 29 was isolated, fully characterized, and illustrated to undergo [3 + 2] reductive cycloaddition upon exposure to methanol [45]. Related pathways have recently been described involving cobalt-catalyzed reductive cyclo additions of enones and allenes [46], suggesting that this novel mechanism may be general for a variety of metals and substrate combinations. 

Allenes behave as somehow special olefins in such photocycloadditions 476a,b,477) Additions of enones to allene have been used as key step in the synthesis of the alkaloids annotinine 478a) (4.65) and chasmanine (4.66) 478b). 

Transmetallation of 12 with a catalytic amount of the higher order cyanocuprate Me2Cu(CN)Li2, in the presence of Me3ZnLi and with slow addition of enone 7 led first to the initial conjugate addition product 14, then to zinc enolate 15 after Cu-to-Zn transmetallation. The third component, the electrophile, either an aide-... 

Ar- 7/-Butoxycarbonyl-2-cyanopiperidines such as 277 undergo reductive decyanation-lithiation with lithium di- v/-butylbiphenylidc (LiDBB) to give a-lithiopiperidines which can then undergo addition of numerous electrophiles, to give 2-substituted piperidines. The addition of aldehydes and ketones results in formation of bicyclic carbamates such as 278. Transmetalation of the initial lithiate, with hexynylcopper, forms the cuprate which results in the formation of the 1,4-addition product 279 upon addition of enones, such as cyclohexenone, while the lithiate gives only 1,2-addition product 280 (Scheme 66) <2004OL2745>. 

Lewis acid catalyzed intramolecular ene reactions with enones or enals sometimes occur in good yield. For instance, MeAlCl catalyzed ene reaction of enone (161) at room temperature gives ene adduct (162) in 85% yield. In many other cases, Lewis acid or proton catalyzed intramolecular additions of enones or enals to alkenes give zwitterions, which yield mixtures of products. - " ... 

In our hands, the regioselectivity was usually high, but it could become variable without careful attention to the conditions. Catalysts and rates of addition of enones influenced product distributions. Regioselectivity, though, was dictated mainly by the relative bulk of the participating amine, with primary and secondary amines mainly affording 2- and 4-substituted anilines, respectively. 

Meinwald and Mioduski76 have studied the photochemistry of the bicyclic ketones (101) which are prepared by addition of enones to cyclobutadiene iron... 

Scheme 12.9 Michael addition of enones with malonates, P-ketoesters or...

Following the same iminium ion activation mode but with cinchona primary-tertiary diamine bifunctional catalyst 9, Chen and co-workers [108] described the asymmetric intramolecular aza-Michael addition of enone carbamates (Scheme 11.29). The reactions proceed in high yield and with good to excellent stereocontrol (up to 99% ee). 

SCHEME 11 9. Asymmetric organocatalytic intramolecular aza-Michael addition of enone carbamates. 

A) CuCN.2LlBr in THE or (B) lithium 2-thienyl-cyanocuprate (0.25M solution in THE). Added at -78°C just prior to the addition of enone. 

To decide whether disconnection (a) or (b) suggests a synthetically more convenient route, we consider the relative reactivities of single reactants. Benzaldehyde is more reactive with the acetonide anion than with enone TM 4.9b. Therefore, in the first step, aldol condensation is preferred, followed by Michael addition of enone to the carbanion of ethyl cyanoacetate. Consequently, retrosynthesis (b) suggests the preferred synthetic route to TM 4.9 (Scheme 4.30). 

Most of the conjugate additions of enones, such as Michael additions or... 

Sugiura et al. tried conjugate reduction of P-amino enone 101 with trichlorosi-lane catalyzed by 94. As a result, 4H-l,3-oxazine 102 is obtained as the major product, whereas the yield of the desired P-amino carbonyl compound 103 is very low (Scheme 32.22). Furthermore, the ee values of both products are totally different. These results imply that the pathways for producing the two products are different. Based on their observations and previous studies on the conjugate addition of enones with trichlorosilane, the authors proposed that while keto amide... 

No product formation was observed upon irradiation at 532 nm where the fullerene is the only lightabsorbing component. Thus, fullerene triplets do not undergo addition to ground-state enones. Instead, the reaction proceeds by the same mechanism operating in the photoaddition of enones to ordinary alkenes," namely stepwise addition of enone triplet excited states to the fullerene via an intermediate triplet 1,4-biradical. 

Strong evidence that regioselectivity in [2-l-2]-photocycloadditions does not follow a simple pattern comes from a study by Lange et al." on addition of enones 26a and 26b to a series of methyl 1-cycloalkene-1-carboxylates ... 

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