Dienol silanes

The low face-selectivity in the previous example can be partially attributed to single-point coordination of the aldehyde to the Lewis acid. Evans and co-workers have used a-alkoxy aldehydes in aldol reactions with much success (Sch. 35) [70]. Thus a variety of silylketene acetals add to 144 in the presence of a copper(bisoxazoline) catalyst with very high selectivity and chemical yields. Reaction with 147, which contains an additional stereoelement, gave a single aldol product 148 with high syn selectivity. The dienol silane 149 also provides high selectivity in the aldol reaction. A square pyramidal model accounts for the observed selectivity. In this model, the substrate binds... 

Oxazaborolidenes. Corey has reported the use of a novel oxazaborolidene complex 41 prepared from borane and A-tosyl (5)-tryptophan. This complex functions in a catalytic fashion in enantioselective, Mukaiyama aldol addition reactions (Scheme 8-3) [17]. The addition of ketone-derived enol silanes 42-43 gives adducts in 56-100% yields and up to 93% ee. The use of 1-trimethylsilyloxycyclo-pentene 43 in the addition reactions to benzaldehyde affords adducts 46 as a 94 6 mixture of diastereomers favoring the syn diastereomer in 92% ee. Addition reactions with dienol silanes 44 furnishes products 47 in up to 82% ee. Corey also demonstrated the use of these adducts as important building blocks for the synthesis of corresponding dihydropyrones treatment of 47 with trifluoroacetic acid affords the cyclic product in good yields. 

In addition to the efficiency exhibited by catalyst 165 with a broad spectrum of aldehydes in acetate aldol addition reactions, this catalyst has been shown to function competently in enantioselective additions of dienol silane 87. The requisite dienolate is readily synthesized from 2,2,6-trimethyl-4H-l,3-dioxin-4-one 84 (diketene-i-acetone adduct) by deprotonation with LDA and quenching with MejSiCl (Eq. 24). Dioxinone 84 is commercially available at a nominal price in addition, the silyl dienolate 87 is easily purified by distillation and stable to prolonged storage. The addition reactions of 87 with aldehydes were conducted with 1-3 mol % of 165 at 0 °C (Eq. 25). A variety of aldehydes serve as substrates and give aldol adducts in 79-97% yields and up to 99% ee after a single recrystallization. 

A catalytic reaction of a-ketophosphonates (557) and heterocyclic dienol silanes (558) has been developed to give potentially bioactive chiral ot-hydroxy phosphonates (559). Unprotected aldol products (560) have been directly obtained in these reactions, without an additional cleavage step to remove the TMS group (Scheme 161). " ... 

Reactions of silyl enol ethers with dialkoxycarbenium ions result in a-formyl ketones (eq 13), much like those achieved above through the use of enolate anions. With a dienol silane (eq 14), regioselective y-formylation is achieved. In extended alkenic systems, cationic cyclization (eq 15) can be realized. ... 

Significant efforts have extended the scope of catalytic enantioselective Mukaiyama aldol addition reactions beyond the acetate and propionate enoxysilanes and have been used traditionally. Recent reports describe novel addition reactions of silyl dienolates along with isobutyrate-derived enol silanes. 

One of the simplest methods for preparation of an a,/J-unsaturated acyl silane is by hydrolysis of a 1-alkoxy-l-trimethylsilylbutadiene, the conjugated dienol ether of a,fi-unsaturated acyl silane, prepared by deprotonation and alkylation of the 1-alkoxydiene (Scheme 42)11. This method is generally limited in application to simple substrates, presumably due to the complexity of preparation of more highly functionalized 1-alkoxy dienes. 

The first example was described in the mid-1980s independently by Jeffery, Hallberg, and others in their work on Heck coupling. The former demonstrated the beneficial role of silver salts in the formation of dienols from allylic alcohols and vinyl iodides, as well as the role of counterion or phase transfer conditions (Scheme 10.28).50 The latter found that silver salts accelerated the reaction between aryl iodide and allyl or vinyl silanes, reinforcing regioselectivity and avoiding desilylation (Scheme 10.29).51... 

Aldol Addition. A catalyst generated upon treatment of Cu(OTf)2 with the (5,5)-r-Bu-box ligand has been shown to be an effective Lewis acid for the enantioselective Mukaiyama aldol reaction. The addition of substituted and unsubstituted enolsilanes at -78 °C in the presence of 5 mol % catalyst was reported to be very general for various nucleophiles, including silyl dienolates and enol silanes prepared from butyrolactone as well as acetate and propionate esters. 

Evans has also reported the addition of a number of other synthetically useful enol silanes. In this regard, the Cu(II)-catalyzed addition of butyrolactone enol silane give the syn diastereomer (96 4 syn/anti) in 92% ee. The addition of dienolates 49 and 89 furnishes acetoacetate adducts in 92-94% yields and 92-97% ee... 

Coupling of reactive alkoxyalkenylsilanes has been applied to the synthesis of medium-sized rings. The cyclic silyl ether 54 was converted to cyclodeca-3,5-dienol (55) at room temperature [104]. In many silane coupling reactions, it has been claimed that ligandless r-allylpalladium chloride is an effective catalyst precursor. Possibly, chloride ion is essential for transmetallation as compared with unreactive Pd(OAc)2. 

Decarboxylation.— During a study of the alkylation of 3-trimethylsilylmethyl-dienolates it is reported that the 3-trimethylsilylbutenoic acid (29) undergoes a facile decarboxylation to give an 8 2 mixture of Z- and -allyl silanes in a yield of 92% (Scheme 23). ... 

Cinchona alkaloid-derived ammonium phenoxides as Lewis base catalysts have been appUed to asymmetric vinylogous Mukaiyama-type aldol reactions (Scheme 14.8) [30]. In the first step of this reaction, silyl compound 14 reacts with ammonium phenoxide to produce ammonium dienolate 15 with generation of trimethyl(phenoxy) silane. The latter part of this reachon mechanism is basically simQar to the reaction mechanism of ammonium fluoride-catalyzed reactions with silyl nucleophiles as shown in Scheme 14.7. This reaction system was also appUed to other asymmetric transformations [6a, 31]. 

Further broadening the methodology, the conversion of a (Z)-2,4-dienyl ether into its ( )-isomer has been exemplified in the presence of Pd(II) (Scheme 17) [35]. Alternatively, the Sakurai reaction was employed by the same authors to convert stereoselectively 2,4-dienyl(trimethyl)silane and aldehyde into 2,4-dienol adducts in the presence of Lewis acid. 

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