O-silyl dienolate

Dicarbonyl compounds,2 The alkylation of O-silyl dienolates is y-regioselec-tive and thus provide a useful route to protected 1,5-dicarbonyl compounds. Examples ... 

A variety of Brpnsted acid sources - benzoic acid, silica gel, 3 A molecular sieves - catalyse vinylogous aldol reactions of O-silyl dienolates, under solvent-free conditions.140... 

Sato/Kaneko [104] and Carreira [105] have independently employed acetoacetate-derived O-silyl dienolates as Si-substituted nucleophiles in asymmetric catalytic aldol reactions. The aldol products, d-hydroxy-/3-ketoesters, and the derived syn- and anti-yS,d-diol esters are ubiquitous structural subunits in biologically active natural products such as the polyene macrolide antibiotics. These structural subunits are also found in chemotherapeutics, most notably compactin analogs [106] that have been studied as... 

A question of regiochemistry arises with O-silylated dienolates derived from a, -unsaturated aldehydes, ketones and esters. The silylated dienolates of crotonaldehyde and its 3-methyl derivative (108) react with acetals in Lewis acid catalyzed conditions at the y-position. This high regioselectivity has been used in the synthesis of vitamin A acetate (Scheme 41). ... 

The catalytic version of this type of reaction was realized by using acetoacetate derived O-silyl dienolate as nucleophiles in the presence of Carreira s catalyst, giving acetoacetate y-adducts in high yields and enantiomeric excesses [119] (Scheme 14.42). The products are ubiquitous structural subunits in biologically active natural products such as the polyene macrolide antibiotic and medicinally important HMG-CoA reductase inhibitors. This aldol addition can also be catalyzed by BINOL-Ti complex in the presence of 4A MS with moderate to good enantioselectivity [120]. The same catalyst system was also efficient in the asymmetric aldol reaction between the aldehydes and Chan s diene [ 1,3-bis-(trimethylsilyloxy)-l-methoxy-buta-1,3-diene] and other related silyl enol ethers [121, 122] (Scheme 14.43) or the functionalized silyl enol ether such as 2-(trimethylsilyloxy)furan with good to excellent enantioselectivities [123]. 

The alkylation of O-silylated dienolates with 1,3-dithienium tetrafluoroborate shows useful y-selectivity [equation (59)]. The y-alkylated products are selectively protected 1,5-dicarbonyl compounds. Unsaturated 1,5-diketones, precursors of various heterocycles, can be prepared by the reaction of the potassium enolates of methyl ketones with acyl keten dithioacetals [equation (60)]. ... 

Hydroperoxylation of silyl dienol ethers was effected by the in t7/ -generated reagent triphenyl phosphite ozonide (Equation 26). The yields are moderate and the products are always accompanied by the hydroxylated equivalents. The mechanism was studied and it was found that the oxygen attached to the carbon came from the central O of the ozonide <2001JOC3548>. 

Moreover, the protocol could be used for a vinylogous Mukaiyama aldol addition and offered a solution to the problem of the asymmetric acetoacetate aldol reaction. Thus, 2 mol% of the catalyst 198 is enough to promote the addition of silyl dienolate 214 to various aldehydes to give, after desilylation, O-protected P-keto-5-hydroxy esters [113]. The protocol is illustrated for an addition to P-stannylpropenal 213. Depending on the enantiomer of the catalyst 198 or ent-198 chosen to mediate the aldol addition, enantiomeric products 215 and ent-215 were obtained in 92% ee. In an elegant convergent total synthesis, both enantiomers were incorporated into macrolactin A, as shown in Scheme 5.65 [114,115]. 

The authors assumed that the catalytically active species might be a copper(I) complex originating from reduction by the silyl dienolate 214. As a consequence, the aldol reaction was performed with the chiral copper(I) complex [Cu(OfBu)-(S)-270], and identical results in terms of the stereochemical outcome were obtained. In addition, the reaction was followed by react IR. The study led to evidence of a copper(I) enolate as the active nucleophile, and the catalytic cycle also shown in Scheme 5.77 was proposed. The reaction of the copper(I) complex Cu(OiBu)-(S)-270 with silyl dienolate 214 represents the entry into the catalytic cycle. Under release of trimethylsilyl triflate, the copper enolate 272 forms, whose existence is indicated by in situ IR spectroscopy. Its exact structure remains unclear, but the description as O-bound tautomer is plausible. Upon reaction with the aldehyde, the copper aldolate 273 is generated, which is then silylated by means of the silyl dienol ether 214 to give the (isolable) silylated alcohol 274 from which the aldol product 271 is liberated during the acidic workup [132b]. 

Aliphatic 3-aza-4-oxa-Cope rearrangement of ester-amide dienolates increases the synthetic utility of anionic [3,3]-sigmatropic rearrangement initiated by N—O bond cleavage. Treatment of the enehydroxylamine 94 with KHMDS in the presence of TMSCl at —80°C provided a mixture of iV,0-disilylated 95 and 0,0-disilylated 96 derivatives (equation 30). Both of these would, on [3,3]-sigmatropic rearrangement, provide the corresponding silyl ethers 97 and 98, from which 99 and 100 are obtained on workup. 

This enolate is more stable than the isomeric 1,3-enolate in which the O substituent is in the 2-position three resonance forms can be written for the former enolate while only two can be written for the latter. Me3SiCl then reacts with the dienolate A at the oxygen atom. The dienol silyl ether C is obtained in this way. Silyl ether C reacts with MeLi—in analogy to the reaction B — A shown in Figure 13.19—via the silicate complex B to give the desired enolate. Note that the product enolate is not accessible by treatment of cyclohexanone with LDA (Figure 13.14). 

A 1,6-silyl migration from C to O was also observed in the reaction of allylepoxysi-lane 326 with t-BuLi in a THF/HMPA (25 1) mixed solvent at low temperature, which afforded 5-silylpentenal 327 (equation 200). It was proposed that an initial proton abstraction from 326 gave w-silyl alkoxide 328, which underwent 1,2-silyl and then 1,6-silyl migrations to afford dienolate 329. Hydrolysis of 329 provided 327 (equation 201). The intramolecular nature of the transformation was suggested because the facile reaction occurred even in very dilute (0.02 lmol-1) and low-temperature (—78°C) conditions467. 

Related reactions were reported by Kuwajima et al. in 1979, who used 2-lithiofuran as a nucleophile. Here, C—O bond cleavage in the fur an shifted the equilibrium toward the carbanion side to give dienol silyl ether derivatives 15 tScheme 6.101. ... 

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