Silyl boronate

The Peterson olefination is known for its better performance compared to the corresponding Wittig process for hindered substrates. This is demonstrated in the first asymmetric synthesis of (+)-maritimol, a member of the stemodane diterpenoids (eq 66). Thus, the key step, a Thorpe-Ziegler annulation, requires a 1,5-dinitrile motif. This is achieved by the generation of an a-silyl boronate, obtained by BuLi deprotonation of trimethylsilylace-tonitrile and subsequent transmetalation with triisopropyl borate, which is then condensed with the tricyclic aldehyde. ... 

Only reaction 1 provides a direct pathway to this chiral molecule the intermediate 2-methyl-butanal may be silylated and reacted with formaldehyde in the presence of the boronated tartaric ester described on page 61. The enantiomeric excess may, however, be low. 

Conversion to a more facile, sulfur-derived, leaving group can be achieved by treatment with sodium thiosulfate or salts of thio and dithio acids (75,87). Under anhydrous conditions, boron tribromide converts the 3 -acetoxy group to a bromide whereas trimethyl silyl iodide gives good yields of the 3 -iodide (87,171,172). These 3 -halides are much more reactive, even when the carboxyl group is esterified, and can be displaced readily by cyano and by oxygen nucleophiles (127). 

Alkyl silyl ethers are cleaved by a variety of reagents Whether the silicon-oxygen or the carbon-oxygen bond is cleaved depends on the nature of the reagent used Treatment of alkoxysilanes with electrophilic reagents like antimony tri-fluonde, 40% hydrofluonc acid, or a boron tnfluonde-ether complex results in the cleavage of the silicon-oxygen bond to form mono-, di-, and tnfluorosiloxanes or silanes [19, 20, 21) (equations 18-20)... 

Scheme 5 details the asymmetric synthesis of dimethylhydrazone 14. The synthesis of this fragment commences with an Evans asymmetric aldol condensation between the boron enolate derived from 21 and trans-2-pentenal (20). Syn aldol adduct 29 is obtained in diastereomerically pure form through a process which defines both the relative and absolute stereochemistry of the newly generated stereogenic centers at carbons 29 and 30 (92 % yield). After reductive removal of the chiral auxiliary, selective silylation of the primary alcohol furnishes 30 in 71 % overall yield. The method employed to achieve the reduction of the C-28 carbonyl is interesting and worthy of comment. The reaction between tri-n-butylbor-... 

Scheme 6a presents the synthesis of fragment 15. Intermediate 15 harbors two vicinal stereogenic centers, and is assembled in a very straightforward manner through the use of asymmetric aldol methodology. Treatment of the boron enolate derived from 21 with 3-[(p-methoxybenzyl)oxy]propanal (22) affords crystalline syn aldol adduct 34 in 87 % yield as a single diastereomer. Transamination to the A-methoxy-A-methylamide,20 followed by silylation of the secondary hydroxyl group at C-19 with triethylsilyl chloride, provides intermediate 15 in 91 % yield. 

Hydroxyboron subphthalocyanine was obtained in very low yield (2%) from chloroboron subphthalocyanine in the presence of sodium hydroxide and a crown ether in refluxing xylene, the major product (8%) being, u-oxo-bis(boron subphthalocyanine).68 Silyl ethers, however, are formed in reasonable yields.68... 

In addition to the boron trifluoride-diethyl ether complex, chlorotrimcthylsilanc also shows a rate accelerating effect on cuprate addition reactions this effect emerges only if tetrahydrofuran is used as the reaction solvent. No significant difference in rate and diastereoselectivity is observed in diethyl ether as reaction solvent when addition of the cuprate, prepared from butyllithium and copper(I) bromide-dimethylsulfide complex, is performed in the presence or absence of chlorotrimethylsilane17. If, however, the reaction is performed in tetrahydrofuran, the reaction rate is accelerated in the presence of chlorotrimethylsilane and the diastereofacial selectivity increases to a ratio of 88 12 17. In contrast to the reaction in diethyl ether, the O-silylated product is predominantly formed in tetrahydrofuran. The alcohol product is only formed to a low extent and showed a diastereomeric ratio of 55 45, which is similar to the result obtained in the absence of chlorotrimethylsilane. This discrepancy indicates that the selective pathway leading to the O-silylated product is totally different and several times faster than the unselective pathway" which leads to the unsilylated alcohol adduct. A slight further increase in the Cram selectivity was achieved when 18-crown-6 was used in order to increase the steric bulk of the reagent. 

The cyclohexyloxy(dimethyl)silyl unit in 8 serves as a hydroxy surrogate and is converted into an alcohol via the Tamao oxidation after the allylboration reaction. The allylsilane products of asymmetric allylboration reactions of the dimethylphenylsilyl reagent 7 are readily converted into optically active 2-butene-l, 4-diols via epoxidation with dimethyl dioxirane followed by acid-catalyzed Peterson elimination of the intermediate epoxysilane. Although several chiral (Z)-y-alkoxyallylboron reagents were described in Section 1.3.3.3.3.1.4., relatively few applications in double asymmetric reactions with chiral aldehydes have been reported. One notable example involves the matched double asymmetric reaction of the diisopinocampheyl [(Z)-methoxy-2-propenyl]boron reagent with a chiral x/ -dialkoxyaldehyde87. 

The use of boron trifluoride-diethyl ether complex as the Lewis acid in these reactions promotes silyl group migration and gives rise to the formation of tetrahydrofurans with excellent stereoselectivity82. 

An interesting example from carbohydrate chemistry is the boron trifluoride-diethyl ether complex catalyzed nucleophilic addition of silyl enol ethers to chiral imines (from n-glyceralde-hyde or D-serinal)22. This reaction yields unsaturated y-butyrolactones with predominantly the D-arabino configuration (and almost complete Cram-type erythro selectivity). 

Geometrically defined a/ -epoxysilanes have been shown (6) to undergo a highly stereoselective rearrangement to silyl enol ethers (see also Chapter 15). This rearrangement is catalysed by boron trifluoride etherate, and seems to involved-opening of the epoxysilane, as shown ... 

Boron trifluoride etherate (1 mmol) was added dropwise to a stirred solution of the epoxysilane (1 mmol) in dichloromethane (5 ml) at -78 °C, and the mixture was stirred for 5min. The reaction mixture was quenched with saturated sodium hydrogen carbonate solution (1 ml), and allowed to warm gradually to ambient temperature. The organic phase was washed with brine (3 x 5 ml), dried and concentrated. The (Z)-epoxysilane gave the (Z)-silyl enol ether (68%, 96 4(Z) (E)), and the (E)-isomer gave the (E)-silyl enol ether (69%, 95 5 ( ) (Z)). 

The boron enolates derived from (5)-4-silylated 2,2-dimethyl-l,3-dioxan-5-one undergo anti diastereoselective aldol reactions which provide access to protected oxopolyols of high stereochemical integrity <96SYN1095>. 

Hepatite Virus NS3/4A having the pyrrolidine-5,5-trans-lactam skeleton [83], starting from (R)- and (S)-methionine, respectively. The key step is the addition of the proper silyl ketene acetal to an iminium ion, e.g., that generated by treatment of the intermediate 177 with boron trifluoride, which provided the adduct 178 with better diastereoselectivity than other Lewis acids. Inhibitors of hepatitis C virus NS3/4A were efficiently prepared by a similar route from (S)-methionine [83]. The addition of indole to a chiral (z-amino iminium ion was a completely diastereoselective step in a reported synthesis of tilivalline, a natural molecule which displays strong cytotoxicity towards mouse leukemia L 1210 [84]. 

The regiochemistry of the hydrozirconation of disubstituted stannyl- [24, 167-170] and silyl- [171] acetylenes and boron- [118, 172-175] and zinc- [34, 126] alkynyl derivatives result in the formation of 1,1-dimetallo compounds. Hydrozirconation of alkynyliodonium salts affords alkenylchlorozirconocenes with the Zr-C bond geminal to the iodonium moiety [176]. These zirconocene complexes allowed the preparation of ( )-trisubstituted olefins (Scheme 8-20). 

Reaction conditions that involve other enolate derivatives as nucleophiles have been developed, including boron enolates and enolates with titanium, tin, or zirconium as the metal. These systems are discussed in detail in the sections that follow, and in Section 2.1.2.5, we discuss reactions that involve covalent enolate equivalents, particularly silyl enol ethers. Scheme 2.1 illustrates some of the procedures that have been developed. A variety of carbon nucleophiles are represented in Scheme 2.1, including lithium and boron enolates, as well as titanium and tin derivatives, but in... 

Z-Boron enolates can also be obtained from silyl enol ethers by reaction with the bromoborane derived from 9-BBN (9-borabicyclo[3.3.1]nonane). This method is necessary for ketones such as 2,2-dimethyl-3-pentanone, which give E-boron enolates by other methods. The Z-stereoisomer is formed from either the Z- or E-silyl enol ether.20... 

The enolates of other carbonyl compounds can be used in mixed aldol reactions. Extensive use has been made of the enolates of esters, thiol esters, amides, and imides, including several that serve as chiral auxiliaries. The methods for formation of these enolates are similar to those for ketones. Lithium, boron, titanium, and tin derivatives have all been widely used. The silyl ethers of ester enolates, which are called silyl ketene acetals, show reactivity that is analogous to silyl enol ethers and are covalent equivalents of ester enolates. The silyl thioketene acetal derivatives of thiol esters are also useful. The reactions of these enolate equivalents are discussed in Section 2.1.4. 

If there is no other interaction, the reaction proceeds through an acyclic TS and steric factors determine the amount of syn versus anti addition. This is the case with BF3, where the tetracoordinate boron-aldehyde adduct does not offer any free coordination sites for formation of a cyclic TS. Stereoselectivity increases with the steric bulk of the silyl enol ether substituent R1.50... 

In general, BF3 -catalyzed Mukaiyama reactions lack a cyclic organization because of the maximum coordination of four for boron. In these circumstances, the reactions show a preference for the Felkin type of approach and exhibit a preference for syn stereoselectivity that is independent of silyl enol ether structure.119... 

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