Silyl enol ether reaction with unsaturated ketones

The reactions proceeded efficiently under mild conditions in short time. The silyl enol ethers reacted with the activated acetals or aldehydes at -78 °C to give predominant erythro- or threo-products [136, 137] respectively. In the same manner, the aldol reaction of thioacetals, catalyzed by an equimolar amount of catalyst, resulted in <-ketosulfides [139] with high diastereoselectivity. In the course of this investigation, the interaction of silyl enol ethers with a,]3-unsaturated ketones, promoted by the trityl perchlorate, was shown to proceed regioselec-tively through 1,2- [141] or 1,4-addition [138]. The application of the trityl salt as a Lewis acid catalyst was spread to the synthesis of ]3-aminoesters [142] from the ketene silyl acetals and imines resulting in high stereoselective outcome. 

Copper-catalyzed reactions of [(tosylimino)iodo]benzene with unsaturated compounds sometimes lead to tosylamidation. Examples include conversions of silyl enol ethers to a-tosylamido ketones [173], and tosylamidation of allylic silanes with loss of the silyl group [190] (Scheme 69). 

Although simple ketones and esters can not be allylated by Pd catalysts, they are allylated with allyl carbonates via their enol ethers of Si and Sn. In the allylation of the silyl enol ether 202 with allyl carbonate 200, transmetallation of 202 with the n-allylpalladium methoxide 201, generated from allyl methyl carbonate (200), takes place to generate the Pd enolates 203 and 204. Depending on the reaction conditions, allyl ketone 205 is formed by the reductive elimination of 203 [100]. When the ratio of Pd Ph3P is small, the a,/i-unsaturated ketone 206 is obtained by -elimination [101]. For example, the silyl enol ether 208 of aldehyde 207 is allylated with allyl carbonate (200) to give a-allylaldehyde 210 via 209. The a-allyl carboxylate 213 is obtained by allylation of ester 211 with allyl carbonate (200), after conversion of ester 211 to the ketene silyl acetal 212 [102], As the silyl group is trapped in these... 

Independently, Yamamoto, Yanagisawa, and others reported the asymmetric aldol reaction using trimethoxysilyl enol ethers.19 The reaction was conducted with aldehydes and trimethoxysilyl enol ethers in the presence of Tol-BINAP-AgF to give the corresponding adducts with high enantioselectivities and diastereoselectiv-ities. They obtained vyra-aldol adducts as major products even when silyl enol ethers derived from cyclic ketones were used. Moreover, when a,(3-unsaturated aldehydes were employed as substrates, 1,2 adducts were obtained exclusively (Table 9.10). From an NMR study and correlation between the E Z ratio of the enol ethers and diastereoselectiviy, they proposed a cyclic transition state (Fig. 9.5). Thus, the reaction of E enol ethers proceeded via a boat form, whereas the reaction of Z enol ethers took place via a chair form. 

Another preparative method for the enone 554 is the reaction of the enol acetate 553 with allyl methyl carbonate using a bimetallic catalyst of Pd and Tin methoxide[354,358]. The enone formation is competitive with the allylation reaction (see Section 2.4.1). MeCN as a solvent and a low Pd to ligand ratio favor enone formation. Two regioisomeric steroidal dienones, 558 and 559, are prepared regioselectively from the respective dienol acetates 556 and 557 formed from the steroidal a, /3-unsaturated ketone 555. Enone formation from both silyl enol ethers and enol acetates proceeds via 7r-allylpalladium enolates as common intermediates. 

Example of use with dimethylphenylsilane (11). A mixture of the (i/l-unsaturated ketone (1.05mmol), dimethylphenylsilane (l.lmmol) and tris(triphenylphosphine)rhodium(i) chloride (0.002 mmol) was heated at 55°C for 1 h. The silyl enol ether was distilled directly from the reaction. 

The reactions with a combination of (DHQ)2-PHAL [or (DHQD)2-PHAL] and /V-halosulfo-namides can be successfully applied to trans-olefins. Especially when the substrates are a,j3-unsaturated esters, high regioselectivity as well as good enantioselectivity is realized (Scheme 55).210,211 The use of an /V-halosulfonamide bearing a smaller A-substituent increases the enantioselectivity.211 n-Propanol/water (1 1) is the solvent of choice. Aminohydroxylation of silyl enol ethers has been successfully performed with DHQD-CL or (DHQD)2-PYR, to give the corresponding a-amino ketones.212... 

Although the saturated ketone can be obtained in nearly quantitative yields, the loss of synthetically valuable functionality is unfavorable and can be overcome by a modification of the tandem sequence. The use of the corresponding unsaturated silyl enol ethers in a tandem hydroformyla-tion/Mukaiyama aldol reaction gives the desired aldol adduct with complete... 

Enantioselective deprotonation can also be successfully extended to 4,4-disubstituted cyclohexanones. 4-Methyl-4-phenylcyclohexanone (3) gives, upon reaction with various chiral lithium amides in THF under internal quenching with chlorotrimethylsilane, the silyl enol ether 4 having a quaternary stereogenic carbon atom. Not surprisingly, enantioselectivities are lower than in the case of 4-tm-butylcyclohexanone. Oxidation of 4 with palladium acetate furnishes the a./i-unsaturated ketone 5 whose ee value can be determined by HPLC using the chiral column Chiralcel OJ (Diacel Chemical Industries, Ltd.)59c... 

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. 

Double silylation is also observed in the reaction of a,/3-unsaturated ketones with a bis(disilanyl)dithiane, resulting in high yields of cyclic silyl enol ethers [Eq. (65)].58 The catalyst for this reaction is a cyclic bis(silyl)pal-ladium(II) bis(ferf-butyl isocyanide) complex. Analogous reactions of ester... 

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). 

Figure 12.24 depicts the oxidation of a silyl enol ether A to give an a,/3-unsaturated ketone B. Mechanistically, three reactions must be distinguished. The first justifies why this reaction is introduced here. The silyl enol ether A is electrophilically substituted by palladium(II) chloride. The a-palladated cyclohexanone E is formed via the intermediary O-silylated oxocarbenium ion C and its parent compound D. The enol content of cyclohexanone, which is the origin of the silyl enol ether A, would have been too low to allow for a reaction with palladium(II) chloride. Once more, the synthetic equivalence of a silyl enol ether and a ketonic enol is the basis for success (Figure 12.24). 

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. 

Silyl enol ethers are quite reactive towards IOB-boron trifluoride (or tetrafluoroboric acid) and can be considered as valuable starting materials for several reactions of synthetic importance. Of special interest is their use for carbon-carbon bond formation 1,4-diketones and unsaturated ketones are the products of such reactions further, they can be transformed to oc-hydroxy, methoxy or trifyloxy ketones. With tetrafluoroboric acid IOB forms a yellow solution containing the highly electrophilic Phi+ OH BF4 , stable up to 0°C. This species reacts readily with silyl ethers of several ketones, notably acetophenones, at —78°C, forming an unstable iodonium ion (ArCOCH2I+ Ph) which with another silyl ether affords 1,4-diketones. 

Butane-1,4-diones and y,8-unsaturated ketones from silyl enol ethers upon reaction with IOB/ HBF4 and a carbon nucleophile... 

Since the excess trimethylsilyl bromide was difficult to remove, an alternative sequence was investigated (Scheme 10). After bromination of the silyl enol ether, the reaction mixture was poured into water to hydrolyze both the trimethylsilyl bromide and the anhydride. On heating this bromoacid as before, an unexpected compound was formed. This can be rationalized as follows The reaction proceeds from the enol form, and the mechanism is formally 1,5 elimination of hydrogen bromide with concomitant loss of carbon dioxide. The second decarboxylation is analogous to the one seen earlier, and would be expected of the a,8-unsaturated ketone. 

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