Enol ethers, silyl boranes

Asymmetric aldol reactions.4 The borane complex 3 can also serve as the Lewis acid catalyst for the aldol reaction of enol silyl ethers with aldehydes (Mukaiyama reactions).5 Asymmetric induction is modest (80-85% ee) in reactions of enol ethers of methyl ketones, but can be as high as 96% ee in reactions of enol ethers of ethyl ketones. Moreover, the reaction is syn-selective, regardless of the geometry of the enol. However, the asymmetric induction is solvent-dependent, being higher in nitroethane than in dichloromethane. 

Silyl enol ethers react with aldehydes in the presence of chiral boranes or other additives " to give aldols with good asymmetric induction (see the Mukaiyama aldol reaction in 16-35). Chiral boron enolates have been used. Since both new stereogenic centers are formed enantioselectively, this kind of process is called double asymmetric synthesis Where both the enolate derivative and substrate were achiral, carrying out the reaction in the presence of an optically active boron compound ° or a diamine coordinated with a tin compound ° gives the aldol product with excellent enantioselectivity for one stereoisomer. Formation of the magnesium enolate anion of a chiral amide, adds to aldehydes to give the alcohol enantioselectively. 

In 1974,Mukaiyama and co-workers reported the first examples of Lewis acid-catalyzed Michael reactions between silyl enolates and a,p-unsaturated carbonyl compounds [33]. Evans and co-workers developed a catalytic asymmetric Michael reaction of silyl enol ethers of thiol esters to alkylidene malonates. For example, the reaction of alkylidene malonate 23 with 2.2 equiv of silyl enol ether 22 was carried out in the presence of 10 mol % of catalyst 25 and 2 equiv of hexa-fluoro-2-propanol (HFIP) in PhMe/CH2Cl2 (3 1) at -78 °C to give the expected adduct 24 in 93% ee (Scheme 5) [34]. Borane complex-catalyzed asymmetric Michael addition has also been reported [35]. 

Several synthetic methods employ the 3-halo indolenine intermediates generated by halogenations as intermediates. Danishefsky and coworkers found that the chlor-oindolenine from the methyl ester of W, W -dibenzyltryptophan can be converted to 2-substituted products using a variety of nucleophiles, including allylic boranes and staimanes, enamines and ester silyl enol ethers [68]. 

The allylborations of vinyl and silyl enol ethers affords 1,4-dienes (Scheme 23.34). The dienes apparently arise from an initial allylboration followed by elimination of the 3-alkoxy- or P-(silyloxy) borane. 

Successful examples of the Mukayama aldol reaction include the use of the thermally stable tris(pentafluorophenyl)borane Lewis acid. Yamamoto and coworkers reported that 2 mol% of (C6Es)3B smoothly catalyzes the Mukaiyama-aldol reaction of various silyl enol ethers or ketene silyl acetals with aldehydes (Equation 45). ... 

Enantioselective condensation of aldehydes and enol silyl ethers is promoted by addition of chiral Lewis acids. Through coordination of aldehyde oxygen to the Lewis acids containing an Al, Eu, or Rh atom (286), the prochiral substrates are endowed with high electrophilicity and chiral environments. Although the optical yields in the early works remained poor to moderate, the use of a chiral (acyloxy)borane complex as catalyst allowed the erythro-selective condensation with high enan-tioselectivity (Scheme 119) (287). This aldol-type reaction may proceed via an extended acyclic transition state rather than a six-membered pericyclic structure (288). Not only ketone enolates but ester enolates... 

The next task undertaken was the creation of the diequatorial vicinal diol. Hydroboration/oxidation of C4 would occur predictably at the electron-rich enol silyl ether double bond, and indeed, compound C6 was obtained in 71% as the only diastereomer. The rationalization for this remarkable stereocontrol was based on the assumption that the transition state was as shown in C5, where the amine-bearing appendage assumed a pseudo axial orientation in order to reduce strain [41]. This results in a flattened boat, as shown, and the preferred approach by borane is therefore anti to the pendant C-10 substituent. 

The same authors have shown that independently prepared cyclohexanone enolate on treatment with borane yields trans-cyclohexane-l,2-diol in 45% yield. 2-Methylcyclohexanone, which can give two enolates under appropriate conditions, may thus be selectively converted into either a mixture of trans-diols (112) and (113) in a ratio of 42 58 or the trans-diol (114). Enol silyl ethers may also be employed as substrates for this reaction. 

---