A,/?-unsaturated carbonyls

As was mentioned in Section 13.2, the [27t + 27i] photocycloaddition of alkenes is an allowed reaction according to orbital symmetry considerations. Among the most useful reactions in this categoty, from a synthetic point of view, are intramolecular [27t + 2ti] cycloadditions of dienes and intermolecular [2ti + 2ti] cycloadditions of alkenes with cyclic a, -unsaturated carbonyl compounds. These reactions will be discussed in more detail in Section 6.4 of Part B. 

In general, reaction of diazomethane with a, -unsaturated carbonyl compounds affords pyrazolines in which the nucleophilic methylene group is attached to the carbon atom of the carbonyl compound. According to Huisgen, the reactions belong to the general class of 1,3-dipolar cycloadditions. 

Fluorinated a., -unsaturated carbonyl compounds also are reactive dipo-larophiles Because ol the highly activating carbonyl substituent, these 1,3-dipolar cycloadditions are rapid and regiospecific Good examples are the additions of... 

A simple approach for the formation of 2-substituted 3,4-dihydro-2H-pyrans, which are useful precursors for natural products such as optically active carbohydrates, is the catalytic enantioselective cycloaddition reaction of a,/ -unsaturated carbonyl compounds with electron-rich alkenes. This is an inverse electron-demand cycloaddition reaction which is controlled by a dominant interaction between the LUMO of the 1-oxa-1,3-butadiene and the HOMO of the alkene (Scheme 4.2, right). This is usually a concerted non-synchronous reaction with retention of the configuration of the die-nophile and results in normally high regioselectivity, which in the presence of Lewis acids is improved and, furthermore, also increases the reaction rate. 

One of the problems related to the Lewis acid activation of a,/ -unsaturated carbonyl compounds for the reaction with a nitrone is the competitive coordination of the nitrone and the a,/ -unsaturated carbonyl compound to the Lewis acid [30]. Calculations have shown that coordination of the nitrone to the Lewis acid can be more feasible than a monodentate coordination of a carbonyl compound. However, this problem could be circumvented by the application of alkenes which allow a bidentate coordination to the Lewis acid which is favored over the monodentate coordination. 

In a similar way, lipases catalyze Michael addition of amines, thiols [110], and even 1,3-dicarbonyl derivatives [111, 112] to a,/ -unsaturated carbonyl compounds (Scheme 5.21). 

Few a-ketosulphoxides 123 were prepared by trapping the enolate anions 124, which are generated by the Michael addition of Grignard reagents to easily available a, -unsaturated carbonyl compounds 125, with methanesulphinyl chloride (equation 65). 

Ordinary Grignard reagents react with a, -unsaturated carbonyl compounds and afford both 1,2-adduct and 1,4-adduct. However, methylsulfonyhnethylmagnesium bromide or p-tolylsulfonylmethylmagnesium bromide gave only 1,2-adducts in the reaction with conjugated carbonyl compounds such as crotonaldehyde, cinnamaldehyde, trans-4-phenyl-3-buten-2-one, benzalacetophenone and l,5-diphenyl-2,4-pentadien-l-one. 

Dimethylsulfonium methylide is both more reactive and less stable than dimethylsulfoxonium methylide, so it is generated and used at a lower temperature. A sharp distinction between the two ylides emerges in their reactions with a, ( -unsaturated carbonyl compounds. Dimethylsulfonium methylide yields epoxides, whereas dimethylsulfoxonium methylide reacts by conjugate addition and gives cyclopropanes (compare Entries 5 and 6 in Scheme 2.21). It appears that the reason for the difference lies in the relative rates of the two reactions available to the betaine intermediate (a) reversal to starting materials, or (b) intramolecular nucleophilic displacement.284 Presumably both reagents react most rapidly at the carbonyl group. In the case of dimethylsulfonium methylide the intramolecular displacement step is faster than the reverse of the addition, and epoxide formation takes place. 

Table VII gives a survey of alkaloids that exhibit the hasubanonine-type cleavage. The characteristic fragmentation pattern of this group, possessing an a,/ -unsaturated carbonyl group in ring C, is significantly different from other groups. In the case of hasubanonine (5) (3), the most abundant and nitrogen-free ion peak was observed at m/z 315, which is important for structure elucidation of this group (2,73).

Many interesting examples of photodimerizations and photocycloadditions of a,/ -unsaturated carbonyls and acid derivatives yielding cyclobutanes have been reported. In this section, as in Section 10.1, we will first discuss photodimerizations and then photocycloadditions. 

Proton and Carbon Spectra of a -Unsaturated Carbonyl Compounds. Characteristic proton and carbon data for a,(3-unsaturated carbonyl compounds are provided in Scheme 5.38. Such spectra are exemplified by the proton and carbon spectra of 4,4,4-trifluorocrotonic acid in Figs. 5.15 and 5.16. 

The stereoselective 1,4-addition of lithium diorganocuprates (R2CuLi) to unsaturated carbonyl acceptors is a valuable synthetic tool for creating a new C—C bond.181 As early as in 1972, House and Umen noted that the reactivity of diorganocuprates directly correlates with the reduction potentials of a series of a,/ -unsaturated carbonyl compounds.182 Moreover, the ESR detection of 9-fluorenone anion radical in the reaction with Me2CuLi, coupled with the observation of pinacols as byproducts in equation (40) provides the experimental evidence for an electron-transfer mechanism of the reaction between carbonyl acceptors and organocuprates.183... 

Through dehydration (Equation 2.2) the branched isomer will yield methacrolein, an a, -unsaturated carbonyl compound. 

Dehydration is undesirable because a, -unsaturated carbonyls are catalyst inhibitors. To make matters worse, phosphines can add to the a, -unsaturated carbonyl (Equation 2.3) to give a product that is a dehydration catalyst, so the deactivation spiral continues. 

Aldehyde dimer may undergo dehydration to give an a, -unsaturated carbonyl. From butanal, the conjugated carbonyl is ethylpropylacrolein (Equation 2.10). The conjugated system of this material competes for coordination sites on the rhodium catalyst so that hydroformylation inhibition is observed.[8] The formation of 2-ethylhex-2-enal can be limited by minimizing the concentration of dimers. Dimers are removed along with the product in a liquid recycle separation system. 

Condensation of benzotriazole with 2-carboxybenzaldehyde gives 3-(benzotriazol-l-yl)phthalide 795 (Scheme 127). The anion derived from phthalide 795 adds to the ft-carbon atom of a,( -unsaturated carbonyl compounds E to produce anion 796 that by intramolecular nucleophilic attack on the phthalide carbonyl group is converted to anion 797. Spontaneous expulsion of benzotriazole from molecules 797 followed by aromatization leads to 1,4-dihydroxy-naphthalenes 798 <1997SC3951>. 

Photoenolization is a frequently encountered process for aromatic and a,/)-unsaturated carbonyl compounds5. Typically, an allylic or benzylic /-hydrogen is abstracted by the... 

The R,S-family 33, and of course its enantiomer, provide high enantioselectiv-ities and activities for the reductions of itaconic and dehydroamino acid derivatives as well as imines [141], The JosiPhos ligands have found industrial applications for reductions of the carbon-carbon unsaturation within a,/ -unsaturated carbonyl substrates [125, 127, 131, 143-149]. In contrast, the R,R-diastereoisomerof30 does not provide high stereoselection in enantioselective hydrogenations [125, 141]. 

Silylketene acetals and enolsilanes can also undergo conjugate addition to a,/ -unsaturated carbonyl derivatives. This reaction is referred to as the Mukaiyama-Michael addition and can also be used as a mild and versatile method for C-C bond formation. As shown in Scheme 8-34, in the presence of C2-symmetric Cu(II) Lewis acid 94, asymmetric conjugate addition proceeds readily, giving product with high yield and enantioselectivity.75... 

Shibasaki s lanthanide-alkaline metal-BINOL system, discussed in Chapters 2 and 3, can also effect the asymmetric conjugate addition reaction. As shown in Scheme 8-35, enantioselective conjugate addition of thiols to a,/ -unsaturated carbonyl compounds proceeds smoothly, leading to the corresponding products with high yield and high ee.76... 

E Emori, T. Arai, H. Sasai, M Shibasaki, A Catalytic Michael Addition of Thiols to a, -Unsaturated Carbonyl Compounds Asymmetric Protonations, J. Am Chem Soc 1998,120, 4043-4044. 

Reduction of a., -unsaturated carbonyl compounds. Hydrosilanes, particularly (QH,)2SiH2, in the presence of Pd(0), and a Lewis acid, particularly ZnCl2, can effect selective conjugate reduction of unsaturated ketones, aldehydes, and carboxylic acid derivatives. Chloroform is the solvent of choice. In addition, 1 equiv. of water is required. Experiments with D,0 and (C6H,),SiD2 indicate that... 

Cycloaddition reactions of electron-rich allenes with some heterodienes take place at the C1-C2 bond of the allene to yield heterocycles, a,Unsaturated carbonyl compounds 185 react with the internal C=C bond of ethoxyallene to afford dihydro-pyrans in moderate yields [150]. 

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