Aldol condensation of silyl enol ethers

Aldol condensation of silyl enol ethers 213 with 214 provided in good yields the condensation products 215 which on treatment with concentrated hydrochloric acid in methanol gave derivatives 216 (Scheme 51) (88S381). 

Fluoride-catalysed aldol condensation of silyl enol ethers... 

Aldol condensation. The aldol condensation of silyl enol ethers with an aldehyde in the presence of 1 (0.1 5 equivalents) results mainly or even exclusively in erythro-adducts (equations I and II) regardless of the stereochemistry of the cnolatc. 

Aldol Condensations. The rhodium complex has been utilized as a catalyst in aldol condensation of silyl enol ethers and... 

Asymmetric aldol reaction of silyl enol ethers. (16,221-222). The use of TiCI4 as promoter of aldol condensation of silyl enol ethers with aldehydes, first reported in 1973 (6,590-591), has seen wide use, but has the drawbacks that 1 cquiv. of the Lewis acid is required and that an asymmetric version requires use of chiral aldehydes or chiral silyl enol ethers. More recently, the combination of a salt and a weak Lewis acid, neither effective catalysts themselves, was found to be effective in catalytic (5-10 mol %) amounts. Further research showed that tin(ll) triflatc when coordinated with a chiral diamine can effect catalytic asymmetric allylation of aldehydes (13,302) and Michael reactions (15,313-314), even though this complex cannot promote aldol condensation. Eventually the combination of tin(Il) triflatc, a chiral diamine,... 

AldolCondensations. Cation-exchanged montmorillonites accelerate the aldol condensation of silyl enol ethers with acetals and aldehydes. Similarly, the aldol reaction of silyl ketene acetals with electrophiles is catalyzed by solid-acid catalysts. Neither report discussed the use of iron montmorillonite for these reactions however, some reactivity is anticipated. 

For some condensations with silylated substrates as starting compounds, trimethylsilyl inflate can be used as a catalyst [103, 104, 105] Atypical example of such a reaction is the aldol type condensation of silyl enol ethers and acetals catalyzed by 1-5 mol% of trimethylsilyl inflate [103] (equation 53)... 

Although in the recent years the stereochemical control of aldol condensations has reached a level of efficiency which allows enantioselective syntheses of very complex compounds containing many asymmetric centres, the situation is still far from what one would consider "ideal". In the first place, the requirement of a substituent at the a-position of the enolate in order to achieve good stereoselection is a limitation which, however, can be overcome by using temporary bulky groups (such as alkylthio ethers, for instance). On the other hand, the ( )-enolates, which are necessary for the preparation of 2,3-anti aldols, are not so easily prepared as the (Z)-enolates and furthermore, they do not show selectivities as good as in the case of the (Z)-enolates. Finally, although elements other than boron -such as zirconium [30] and titanium [31]- have been also used succesfully much work remains to be done in the area of catalysis. In this context, the work of Mukaiyama and Kobayashi [32a,b,c] on asymmetric aldol reactions of silyl enol ethers with aldehydes promoted by tributyltin fluoride and a chiral diamine coordinated to tin(II) triflate... 

Carbonyl activation and deactivation.1 Aldehydes, but not ketones, undergo aldol condensation with silyl enol ethers at —78° in the presence of dibutyltin bistriflate. In contrast, the dimethyl acetals of ketones, but not of aldehydes, can undergo this condensation (Mukaiyama reaction) with silyl enol ethers at -78° with almost complete discrimination, which is not observed with the usual Lewis-acid catalysts. Thus dibutyltin bistriflate activates aldehydes, but deactivates acetals of... 

For example, condensation of silyl enol ether (3.21) of 3-pentanone with 2-methylbutanal in the presence of TiC gives the Ti-complex 3.22, which on hydrolysis yields an aldol product, manicone (4,6-dimethyl-4-octen-3-one) (3.23), an alarm pheromone. Treatment of 3-pentanone with LDA results in the formation of an enolate, which is trapped with chlorotrimethylsilane to give 3.21. Other Lewis acids such as tin tetrachloride (SnCU) and boron trifluoride etherate (BF3-OEt2) can also be used. 

Aldol-type condensation of silyl enol ethers with acetals under the influence of la is rather familiar. Unlike the Mukaiyama aldol reaction, 1-5 mol % loading of la is enough to complete the coupling reaction under mild conditions [20]. This transformation is applicable to the synthesis of a wide variety of / -alkoxy carbonyl substrates and has three characteristic features ... 

Cationic Pd complexes can be applied to the asymmetric aldol reaction. Shibasaki and coworkers reported that (/ )-BINAP PdCP, generated from a 1 1 mixture of (i )-BINAP PdCl2 and AgOTf in wet DMF, is an effective chiral catalyst for asymmetric aldol addition of silyl enol ethers to aldehydes [63]. For instance, treatment of trimethylsi-lyl enol ether of acetophenone 49 with benzaldehyde under the influence of 5 mol % of this catalyst affords the trimethylsilyl ether of aldol adduct 113 (87 % yield, 71 % ee) and desilylated product 114 (9 % yield, 73 % ee) as shown in Sch. 31. They later prepared chiral palladium diaquo complexes 115 and 116 from (7 )-BINAP PdCl2 and (i )-p-Tol-BINAP PdCl2, respectively, by reaction with 2 equiv. AgBF4 in wet acetone [64]. These complexes are tolerant of air and moisture, and afford similar reactivity and enantioselec-tivity in the aldol condensation of 49 and benzaldehyde. Sodeoka and coworkers have recently developed enantioselective Mannich-type reactions of silyl enol ethers with imi-nes catalyzed by binuclear -hydroxo palladium(II) complexes 117 and 118 derived from the diaquo complexes 115 and 116 [65]. These reactions are believed to proceed via a chiral palladium(fl) enolate. 

Aldol-type reactions. The highest anti selectivity is observed with BINAP complex of Pd(OTf)j in the aldol reaction of tin enolate of cyclohexanone. The condensation of silyl enol ethers with imines provides y-keto a-amino esters. ... 

Other important aldol condensations are the Mukaiyama-type aldol reactions of silyl enol ethers with aldehydes that usually require catalyst activation. Yamamoto reported that such reactions under high pressure proceed (i) without catalyst even at room temperature, (ii) without isomerization of the formed adducts and (iii) with a reversed synlanti stereoselectivity compared with that of the TiCU-catalysed reactions. ... 

The pinwheel shape of a f-butyl propionate derived silylketene acetal (see Section 2.4.2.1) was revealed by a single-crystal X-ray diffraction analysis. Several different catalysts were reported to promote the aldol-type condensation of alkyl enol ethersand silyl enol ethers with aldehydes, acetals and various other electrophiles. In some cases the reaction proceeded with high simple stereoselection. The mechanism of the Lewis acid mediated additions to acetals (see Section 2.4.2.3) was investigated in detail, as well as the uncatalyzed aldol reaction of silyl enol ethers with aldehydes promoted by the hydrophobic effect (see Section 2.4.2.1). 

There has been a quite limited number of reports of clay-catalysed aldol condensations. One of the more interesting of these is the aluminium-exchanged montmorillonite (Al3+-mont) catalysed cross-aldol reaction of silyl enol ethers with aldehydes (Reaction 6).34 The reaction proceeded smoothly under mild conditions to give the corresponding aldol adduct in good yield. 

Mukaiyama aldol reactions With Cu(OT02 as catalyst, the condensation of silyl enol ethers with aldehydes can be carried out in aqueous ethanol. 

TMSOTf mediates a stereoselective aldol-type condensation of silyl enol ethers and acetals (or orthoesters). The nonbasic reaction conditions are extremely mild. TMSOTf catalyzes many aldol-type reactions in particular, the reaction of relatively non-nucleophilic enol derivatives with carbonyl compounds is facile in the presence of the silyl triflate. The activation of acetals was first reported by Noyori and has since been widely employed (eq 14). ... 

Mikami reported that BINOL derived titanium complex efficiently catalyzed the aldol reaction of silyl enol ether with excellent control of both absolute and relative stereochemistry [106] (Scheme 14.37). The reaction was proposed to proceed via a prototropic ene reaction pathway that is different from that of Mukaiyama aldol condensation. A cyclic antiperiplanar transition-state model was proposed to explain the pref erential formation of the syn diastereomer from either (E)- or (Z)-silyl enol ethers [106]. Further modifications of the catalyst system include the use of perfluorophenols and other activating additives [107], or performing the reaction in supercritical fluids [108]. Furthermore, the nucleophile could be extended to enoxysilacyclobutane derivatives [109]. 

The aldol or aldol-type reaction is well recognized as one of the most important carbon-carbon bond forming reactions in organic synthesis. As shown in Scheme 8.1, two stereogenic centers could be generated in this aldol reaction. The classical aldol condensation between an aldehyde and a ketone is often catalyzed by a base or an acid. Another approach is the acid-catalyzed cross-aldol reaction of silyl enol ethers with carbonyl compounds, the so-called Mukaiyama reaction. 

Mukiayama aldol reactions between silyl enol ethers and various carbonyl containing compounds is yet another reaction whose stereochemical outcome can be influenced by the presence of bis(oxazoline)-metal complexes. Evans has carried out a great deal of the work in this area. In 1996, Evans and coworkers reported the copper(II)- and zinc(II)-py-box (la-c) catalyzed aldol condensation between benzyloxyacetaldehyde 146 and the trimethylsilyl enol ether [(l-ferf-butylthio)vinyl]oxy trimethylsilane I47. b82,85 Complete conversion to aldol adduct 148 was achieved with enantiomeric excesses up to 96% [using copper(II) triflate]. The use of zinc as the coordination metal led to consistently lower selectivities and longer reaction times, as shown in Table 9.25 (Eig. 9.46). 

Vinyloxyboranes (boron enolates) are obtained in quantitative yield by reaction of silyl enol ethers with dialkylboron triflates in CH2C12 at —22 . The products can be used for stereoselective aldol condensations.3 Example ... 

The Mukaiyama aldol reaction of carbonyl substrates with silyl enol ethers is the most widely accepted of Lewis acid-promoted reactions. Many Lewis acids for the reaction have been developed and used enantioselectively and diastereoselectively. In 1980, catalytic amounts of la were found by Noyori et al. to effect aldol-type condensation between acetals and a variety of silyl enol ethers with high stereoselectivity [2c,20]. Unfortunately, la has poor Lewis acidity for activation of aldehydes in Mukaiyama s original aldol reaction [21]. Hanaoka et al. showed the scope and limitation of 11-cat-alyzed Mukaiyama aldol reaction, by varying the alkyl groups on the silicon atom of silyl enol ethers [22]. Several efforts have been since been made to increase the reactivity and/or the Lewis acidity of silicon. One way to enhance the catalyst activity is to use an additional Lewis acid. 

Because the aldol reaction is one of the most fundamental bond-construction processes in organic synthesis [86], much attention has been focused on the development of asymmetric catalysts for aldol reactions, using silyl enol ethers of ketones or esters as storable enolate components (the Mukaiyama aldol condensation) [87]. 

Aldol reactions. The enantioselectivity in condensations involving silyl enol ethers and silyl ketene acetals (also thioacetals) has been actively pursued. Valuable catalysts include 102, 103. Subsequent to the development of Cj-symmetric... 

The so-called silyl enol ethers (enoxyorganylsilanes) are important synthones, e.g, for regiospecific preparation of enolates, aldol condensation, synthesis of a-substituted carbonyl derivatives and for thermal or photochemical cycloaddition. For the preparation of silyl enol ethers the corresponding aldehydes and ketones first have to be enolized and then treated with silylating agents in the presence of a base. Thus, from butanal (608) and Me3SiCl, cis/trans- 1-trimethylsiloxybut-l-ene (609) is obtained (equation 311)347, while 1-trimethylsiloxy-l-phenylethene (610) is the product from acetophenone (90a) (equation 312)347. 

Enoxysilacyclobutanes. These compounds can be prepared by Wurtz coupling of 3-chloropropyltrichlorosiIane with Mg in ether. Introduction of one alkyl group is accomplished by reaction with an organolithium reagent, and the silyl chloride can then be used for the formation of silyl enol ethers. Such 0-silyl ketene acetals are extremely reactive in aldol condensations with aldehydes without catalysts. The reaction is syn-selective. An asymmetric version uses silyl ketene acetals bearing a chiral Si-alkoxy (e.g., 8-phenylmenthoxy) group instead of an alkyl substituent. 

The chiral acyloxyborane 7 (CAB) has also been found to be an excellent catalyst for asymmetric Mukaiyama-Michael type aldol reaction between silyl enol ethers and aldehydes (Scheme 8). Yamamoto et al. [27] have used 20 mol % of CAB in propionitrile at -78 °C as a highly efficient catalyst for the condensation of several E and Z silyl enol ethers and ketene acetals with a variety of aldehydes (yields 49-97 %, 80-97 % ee). 

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