Unsaturated carbonyl compounds silyl enol ethers

Preparation of o,/3-Unsaturated Carbonyl Compounds by the Reactions of Silyl Enol Ethers and Enol Acetates with Ally Carbonates... 

Rhodium-catalysed addition (10) of hydridosilanes (Chapter 17) to a/3-unsaturated carbonyl compounds can be performed regioselectively, to afford either the product of 1,2-addition, or, perhaps more usefully, that of 1,4-addition, i.e. the corresponding silyl enol ether this latter process is an excellent method for the regiospecific generation of silyl enol ethers. Of all catalyst systems investigated, tris(triphenylphosphine)rhodium(l) chloride proved to be the best. 

The ring-opening of the cyclopropane nitrosourea 233 with silver trifiate followed by stereospecific [4 + 2] cycloaddition yields 234 [129]. (Scheme 93) Oxovanadium(V) compounds, VO(OR)X2, are revealed to be Lewis acids with one-electron oxidation capability. These properties permit versatile oxidative transformations of carbonyl and organosilicon compounds as exemplified by ring-opening oxygenation of cyclic ketones [130], dehydrogenative aroma-tization of 2-eyclohexen-l-ones [131], allylic oxidation of oc,/ -unsaturated carbonyl compounds [132], decarboxylative oxidation of a-amino acids [133], oxidative desilylation of silyl enol ethers [134], allylic silanes, and benzylic silanes [135]. 

Michael addition of various a,fi-unsaturated carbonyl compounds to silyl enol ether catalyzed by Ti-beta and TS-1... 

Adapted from Sasidharan and Kumar (257). Reaction conditions catalyst, 150 mg methyl trimethylsilyl dimethylketene acetal (silyl enol ether), 10 mmol a,(3-unsaturated carbonyl compounds, 10 mmol dry THF, 10 mmol reaction temperature, 333 K reaction time, 14 h. Structures of a, p-unsaturated carbonyl compounds (2a-2g) and products (3a-3g) are shown in Scheme 24. 

Conjugate reduction.1 This stable copper(I) hydride cluster can effect conjugate hydride addition to a,p-unsaturated carbonyl compounds, with apparent utilization of all six hydride equivalents per cluster. No 1,2-reduction of carbonyl groups or reduction of isolated double bonds is observed. Undesirable side reactions such as aldol condensation can be suppressed by addition of water. Reactions in the presence of chlorotrimethylsilane result in silyl enol ethers. The reduction is stereoselective, resulting in hydride delivery to the less-hindered face of the substrate. 

Toyota, Ihara, and coworkers demonstrated that silyl enol ethers undergo Pd -promoted intramolecular nucleophilic attack on alkenes [18]. Allhough early examples required stoichiometric Pd [167], they have also shown that Pd(OAc)2 in DMSO is an effective catalyst in the presence of an aerobic atmosphere (Eq. 38) [168-170]. The reaction is proposed to proceed through an oxo-jt-allyl intermediate that can undergo competitive alkene insertion or P-hydride elimination (Scheme 11). The latter reaction is the basis for the synthetically useful conversion of silyl enol ethers to a,P-unsaturated carbonyl compounds (see below). Efforts to use BQ as an oxidant were not described. 

The conjugate addition of bis(iodozincio)methane to -unsaturated carbonyl compound gives y-zincio substituted enolate. As shown in equation 31, bis(iodozincio)methane reacts with. v-cis a,/3-unsaturated ketone in the presence of chlorotrimethylsilane to afford the silyl enol ether carrying a C—Zn bond. These zinc-substituted silyl enolates can be used for further coupling reactions (equation 32)54. 

Unsaturated 1,5-dicarbonyl compounds. The phenylthioalkylation of silyl enol ethers of carbonyl compounds (9, 521-522) can be extended to the synthesis of unsaturated 1,5-dicarbonyl compounds. In a typical reaction the enol silyl ether of a ketone is alkylated with the unsaturated chloride 1 under ZnBr2 catalysis to give a homoallyl sulfide. Ozonolysis of the methylene group is accompanied by oxidation of the phenylthio group sulfoxide elimination results in an unsaturated 1,5-aldehydo ketone (equation I). Alkylation with 2 results in a methyl ketone (equation II). 

According to Section 12.3 enamines are just one synthetic equivalent for enols that are not sufficiently represented in equilibrium with a carhonyl compound to allow for a-functional-izations. Enol ethers and silyl enol ethers, which are addressed in this section, are other synthetic equivalents for such enols. An enol ether, for example, is used as an enol equivalent for aldehyde enols, since several aldehydes do not form stable enamines. In addition, enol ethers or silyl enol ethers are usually employed as synthetic equivalents for the enols of ,/i-unsatu-rated carbonyl compounds. The attempt to react ce,/ -unsaturated carhonyl compounds with secondary amines to give a dienamine is often frustrated by a competing 1,4-addition of the amine. The combination of these factors turns the dienol ether B of Figure 12.23 into a species for which there is no analog in enamine chemistry. 

The reactions of silenes with aldehydes and ketones is another area whose synthetic aspects have been particularly well-studied4,6 7 10 12. The favoured reaction pathways for reaction are generally ene-addition (in the case of enolizable ketones and aldehydes) to yield silyl enol ethers and [2 + 2]-cycloaddition to yield 1,2-siloxetanes (equation 44), but other products can also arise in special cases. For example, the reaction of aryldisilane-derived (l-sila)hexatrienes (e.g. 21a-c) with acetone yields mixtures of 1,2-siloxetanes (51a-c) and ene-adducts (52a-c) in which the carbonyl compound rather than the silene has played the role of the enophile (equation 45)47,50 52 98 99. Also, [4 + 2]-cycloadducts are frequently obtained from reaction of silenes with a,/i-unsaturated- or aryl ketones, where the silene acts as a dienophile in a formal Diels-Alder reaction6 29,100-102. 

Phenylthioalkylation of silyl enol ethers. Silyl enol ethers of ketones, aldehydes, esters, and lactones can be alkylated regiospecifically by a -chloroalkyl phenyl sulfides in fhe presence of a Lewis acid. Zinc bromide and titanium(IV) chloride are the most effective catalysts. The former is more satisfactory for enol ethers derived from esters and lactongs. ZnBr2 and TiCL are about equally satisfactory for enol ethers of ketones. The combination of TiCL and Ti(0-f-Pr)4 is more satisfactory for enol ethers of aldehydes. Since the products can be desulfurized by Raney nickel, this reaction also provides a method for alkylation of carbonyl compounds. Of more interest, sulfoxide elimination provides a useful route to a,B-unsaturated carbonyl compounds. 

In addition to enol silyl ethers, other derivatives of aldehydes and ketones, i.e. enol ethers (Eq. 8) [48] and enol esters (Eq. 9) [49, 50], serve as a partners for the cross aldol reaction, although the lower reactivity of these compounds compared with enol silyl ethers often makes the reaetion more complicated. For example, the products isolated in Eq. (8) were ether derivatives or a,y8-unsaturated carbonyl compounds rather than the expected aldol itself. 

If the reaction between enol silyl ethers and a,/ -unsaturated ketones is attempted in the presence of a titanium Lewis acid, the mode of the reaction switches to 1,4-addition with reference to the unsaturated ketone [109-113]. The reaction of an enol silyl ether is shown in Eq. (30) [114]. Ketene silyl acetals react with a,j8-unsaturated ketones in similar 1,4-fashion, as exemplified in Eq. (31) [115]. Acrylic esters, which often tend to polymerize, are also acceptable substrates for a, -unsaturated carbonyl compounds [111]. A difluoroenol silyl ether participated in this cationic reaction (Eq. 32) [116], and an olefinic acetal can be used in place of the parent a-methylene ketone [111] to give the 1,5-diketone in good yield (Eq. 33) [117]. More results from titanium-catalyzed 1,4-addition of enol silyl ethers and silyl ketene acetals to a,f -unsaturated carbonyl compounds are summarized in Table 4. 

Michael reactions of silyl enolates or ketene silyl acetals with a, -unsaturated carbonyl compounds are among the most important carbon-carbon bond-forming processes in organic synthesis. Sc(OTf)3 was found to be effective [4], and the reactions proceeded smoothly in the presence of a catalytic amount of Sc(OTf)3, under extremely mild conditions, to give the corresponding 1,5-dicarbonyl compounds in high yields after acid work-up (Eq. 2). Silyl enolates derived from ketones, thioesters, and esters were applicable, and no 1,2-addition products were obtained. The products could, furthermore, be isolated as synthetically valuable silyl enol ethers (I) when acid-free work-up was performed. The catalyst could be recovered almost quantitatively and could be re-used. 

The stable, well-characterized copper(I) hydride cluster [(PPh3)CuH]6 is a useful reagent for conjugate reduction of a,p-unsaturated carbonyl compounds. o This hydride donor is chemically compatible with chlorotrimethylsilane, allowing formation of silyl enol ethers via a reductive silation process (Scheme 53). 

Again, much efficiency was gained by switching from alkoxy to siloxycyclopropanes . Dibromocarbene addition to silyl enol ethers generates cyclopropanes which open to a-bromo a,j5-unsaturated carbonyl compounds on thermolysis or treatment with acid in methanol (equation 137) . It has been shown that this homologation process also works for siloxycyclopropanes obtained by addition of other carbenoids (equation and that it is useful for terpene preparation . ... 

The Michael addition (1,4-conjugate addition) of an enolate to an ot, -unsaturated carbonyl system is another prevalent reaction for carbon-carbon bond formation (75, 76). However, its use in organic syntheses is occasionally restricted owing to a concurrent 1,2-addition reaction and polymerization of a, -unsaturated carbonyl compounds. A new methodology to overcome these problems has been devised by the use of lithium enolates (77-79). Another approach is to use silyl enol ethers and silyl ketene acetals as enolates. 

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