A,P-Unsaturated compound

Reaction conditions depend on the reactants and usually involve acid or base catalysis. Examples of X include sulfate, acid sulfate, alkane- or arenesulfonate, chloride, bromide, hydroxyl, alkoxide, perchlorate, etc. RX can also be an alkyl orthoformate or alkyl carboxylate. The reaction of cycHc alkylating agents, eg, epoxides and a2iridines, with sodium or potassium salts of alkyl hydroperoxides also promotes formation of dialkyl peroxides (44,66). Olefinic alkylating agents include acycHc and cycHc olefinic hydrocarbons, vinyl and isopropenyl ethers, enamines, A[-vinylamides, vinyl sulfonates, divinyl sulfone, and a, P-unsaturated compounds, eg, methyl acrylate, mesityl oxide, acrylamide, and acrylonitrile (44,66). 

Synthesis of 4,6-disubstituted-2-picolines and their corresponding nicotinamides has been developed using (3-arninocrotoriitrile (52) and a, P-unsaturated compounds, where = aryl (51). 

Vinyllithium [917-57-7] can be formed direcdy from vinyl chloride by means of a lithium [7439-93-2] dispersion containing 2 wt % sodium [7440-23-5] at 0—10°C. This compound is a reactive intermediate for the formation of vinyl alcohols from aldehydes, vinyl ketones from organic acids, vinyl sulfides from disulfides, and monosubstituted alkenes from organic halides. It can also be converted to vinylcopper [37616-22-1] or divinylcopper lithium [22903-99-7], which can then be used to introduce a vinyl group stereoselectively into a variety of a, P-unsaturated systems (26), or simply add a vinyl group to other a, P-unsaturated compounds to give y, 5-unsaturated compounds. Vinyllithium reagents can also be converted to secondary alcohols with trialkylb o r ane s. 

Read ions of Heterocyclic Enamines with a,p-Unsaturated Compounds Enamines react readily with compounds containing a double bone activated by electronegative groups. Addition of acrolein to 1-methyl-2 ethylidenepyrrolidine, followed by dehydrogenation, leads to 1,7-dimethyl indole (133) (Scheme 9) (215). 

The utilization of phosphine-boranes as stable forms of the phosphine has been exploited for addition reactions with alkenes. With several types of a,P-unsaturated compounds, Michael addition of primary phosphine-boranes has been accomplished in excellent yield for the preparation of secondary phosphine-boranes (Equation 3.30).443... 

Although transition metal-mediated P-H addition across ordinary alkenes proceeds well only with five-membered cyclic hydrogen phosphonates, addition across the olefinic linkage of a,P-unsaturated compounds occurs readily with a range of phosphorus species and catalytic agents. Of particular note are the reaction systems involving platinum,96-107 palladium,108-115 and the lanthanides.116-122... 

Friedman, M., Cavins, I.F., and Wall, l.S. Relative nucleophilic reactivities of amino groups and mercaptide ions in addition reactions with a.p-unsaturated compounds, J. Am. Chem. Soc., 87(16) 3672-3682,1965. 

Hexamethylbiguanide (CLXIX) reacts additively in acetonitrile with a,P Unsaturated compounds activated by an electron-withdrawing group (e.g. with vinyl cyanide) to yield saturated adducts (CLXX). By a suitable choice of reagents, adducts bearing substituents other than the nitrile group (e.g. carbamoyl, carbalkoxy) are accessible 213) ... 

Addition of Organometallic Reagents to Enones in Aqueous Media Rhodium-catalyzed 1,4-addition of organometallic reagents to a,p-unsaturated compounds was first developed by Miyaura in 1997. Thus, Rh(acac)(CO)2/dppb was found to catalyze the 1,4-addition of aryl- and alkenylboronic acids to several ot,(3-unsaturated ketones in water-containing solvents at 50°C. The reaction conditions were successfully modified for the development of an asymmetric variant of this process by Hayashi and Miyaura in 1998. The important points of modification are (1) the use of Rh(acac)(C2H4)2/(5)-binap as a catalyst and... 

Rhodium-catalyzed asymmetric 1,4-addition reactions have been applied to various other a,p-unsaturated compounds as well. Thus, Rh/(5)-binap can catalyze the asymmetric 1,4-addition of arylboroxines to ot,p-unsaturated phosphonates in high yield and ee (Figure 3.37). The key to the success in achieving high yield is the... 

Further examples in Table 6.6 show that, depending on the substitution pattern, the cycloaddition of nitrile oxides to various a,p-unsaturated compounds can lead to different ratios of regioisomeric adducts. 

The condensation of carbon acid compounds with aldehydes to afford a,p-unsaturated compounds. 

The Stetter Reaction is a 1,4-addition (conjugate addition) of an aldehyde to an a,p-unsaturated compound, catalyzed by cyanide or a thiazolium salt. This reaction competes with the corresponding 1,2-addition, which is the Benzoin Condensation. However, the Benzoin-Condensation is reversible, and since the Stetter Reaction leads to more stable products, the main product will be derived from 1,4-addition. 

An iridium catalyst (52) has been found to catalyse H-D exchange in a variety of unsaturated carboxylic acids, ketones and amines.155 The mechanism presumably involves displacement of cyclooctadiene by a solvent molecule, which later on is replaced by the a,p-unsaturated compound. 

The synthons 9 and 15 have natural polarity and it will be helpful in the next 10 chapters if you recognise whether synthons such as these and 17 have natural polarity. We have discussed 9 and 15 above and 17 in chapters 6 and 13 where we used a,p-unsaturated compounds 18 as electrophiles. You may find it helpful to use the labels suggested by Seebach.1 The letters a and d are used for acceptor (electrophilic) and donor (nucleophilic) synthons and a superscript number shows which atom is meant. The carbonyl group is always atom number 1. So the enolate becomes a d2 synthon and 9 and 17 are a1 and a3 synthons. If you don t like these labels, ignore them, they are entirely optional. 

Scheme 39 General reaction scheme illustrating the multistep synthesis of an a,P-unsaturated compound.

On the other hand, reduction of a,p-unsaturated compounds under the same conditions leads to the corresponding saturated ketones. This result can be reached in two cases of industrial interest such as the reduction of P-ionone into dihydro-P-ionone (entry 3), a valuable intermediate for the flavors and fragrances industry, and the reduction of 4-(6-methoxy-2-naphthyl)-3-buten-2-one into nabumetone (entry 4), a nonsteroidal anti-inflammatory drug [33], The selective hydrogenation of P-ionone can be performed in 89% yield using Raney nickel alloy treated with sodium hydroxide [34], with a Ru-C catalyst [35] or with Ph3SnH [36]. On the other hand Pd/C [37, 38] and Rh(T0A)/Al203 systems [39] are reported to be selective for the preparation of nabumetone. 

D. Caine, Reduction and Related Reactions of a,p-Unsaturated Compounds with Metals in Liquid Ammonia, Org. React. 1976, 23, 1—258. 

The reduction of methyl 2-siloxycyclopropanecarboxylates can also be started at the ester function when lithium aluminum hydride in ether is the reagent. The resulting alcohols undergo the wellknown cyclopropylcarbinyl/homoallyl rearrangement upon treatment with acid to provide P/y-unsaturated carbonyl compounds 117. These are synthesized isomerically pure and in good yields in a number of cases, if the two-phase-system 2N hydrochloric acid/pentane is employed 78). Otherwise the very easy isomerization to the conjugated a,p-unsaturated compounds 118 occurs to some extend, which can intentionally be completed by base catalysis. 

The reaction of salicylaldehydes with a,P-unsaturated compounds which can lead to chromenes, chromans and other heterocycles has been reviewed <07OBC1499> and details of their reaction with allenic esters and ketones have been published <07CEJ3701>. A proline-catalysed benzoic acid-promoted asymmetric synthesis of chromene-3-carbaldehydes involves a domino oxa-Michael - aldol reaction with a,P-unsaturated aldehydes the ee range is 83-98% (Scheme 11) <07CEJ574>. 

Stable enolates are Michael donors, and a,p-unsaturated compounds are Michael acceptors. 

When aromatic aldehydes are condensed with nitroalkanes in the presence of a base, a, p-unsaturated nitro compounds are produced directly. For example, benzaldehyde and nitromethane in the presence of a base give a,p-unsaturated compound nitrostyrene (3.25). Similarly, the reaction of nitrobutane with furfural in the presence of a base followed by hydrolysis gives 82% yield of 2-substituted furan derivative 3.26. 

Procedures have been developed for the phenylselenenylation and oxidative elimination of P-formyl ketones and aldehydes to form the corresponding a,p-unsaturated aldehydes (Schemes 29 and 30). Other P-dicarbonyl compounds have also been oxidized to the corresponding a,P-unsaturated compounds by phenylselenenylation and oxidative elimination including 3-(l-oxotrienyl)pyrrolidinones,... 

Epoxidation of a,p-unsaturated compounds. Marmor found that on addition of Chlorox to a solution of benzalacetophenone in pyridine the yellow color faded almost immediately and addition of water precipitated the epoxide in high yield. 

Table 3.3 Michael addition of different nitroalkanes to a,p-unsaturated compounds catalysed by SiO2 (Clhla NBI2 (see Scheme 3.14).

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