Borinate, enol synthesis

Among the preformed enol derivatives used in this way have been enolates of magnesium, lithium, titanium, zirconium, and tin, ° silyl enol ethers, enol borinates,and enol borates, R CH=CR"—OB(OR)2. The nucleophilicity of silyl enol ethers has been examined. In general, metallic Z enolates give the syn (or erythro) pair, and this reaction is highly useful for the diastereoselective synthesis of these products. The ( ) isomers generally react nonstereoselectively. However, anti (or threo) stereoselectivity has been achieved in a number of cases, with titanium enolates, with magnesium enolates, with certain enol bor-inates, and with lithium enolates at — 78°C. ... 

The syntheses in Schemes 13.45 and 13.46 illustrate the use of oxazolidinone chiral auxiliaries in enantioselective synthesis. Step A in Scheme 13.45 established the configuration at the carbon that becomes C(4) in the product. This is an enolate alkylation in which the steric effect of the oxazolidinone chiral auxiliary directs the approach of the alkylating group. Step C also used the oxazolidinone structure. In this case, the enol borinate is formed and condensed with an aldehyde intermediate. This stereoselective aldol addition established the configuration at C(2) and C(3). The configuration at the final stereocenter at C(6) was established by the hydroboration in Step D. The selectivity for the desired stereoisomer was 85 15. Stereoselectivity in the same sense has been observed for a number of other 2-methylalkenes in which the remainder of the alkene constitutes a relatively bulky group.28 A TS such as 45-A can rationalize this result. 

Perhaps the best general method to date for preparing a-haloacyl silanes involves bromi-nation of silyl enol borinates (9) at 0 °C, a reaction which proceeds in good yield and involves no sensitive intermediates. This route offers a most convenient one-pot synthesis of a-haloacyl silanes from readily available starting materials, as the intermediate enol borinates are very easily prepared from silyl acetylenes (Scheme 35)7,117,118. 

An effective control of the simple diastereoselectivity in boron-mediated aldol reactions of various propionate esters (162) was achieved by Abiko and coworkers (equation 45) °. They could show that under usual enolization conditions (dialkylboron triflate and amine) enol borinates are formed, which allowed the selective synthesis of 5yw-configured aldol products (Table 11). The enolization at low temperature (—78 °C) generated a (Z)-enolate selectively, which afforded mainly the syn diastereomer 164 after reaction with isobu-tyraldehyde (163), following a Zimmerman-Traxler transition-state. The anti diastereomer 164 instead was obtained only in small amounts (5-20%). 

A specific example of the process, useful for the synthesis of phenyl ketones, is shown in equation (34). Unfortunately, the further reactions of the intermediate enol borinates (36) with aldehydes show little diastereoselectivity (equation 33). ... 

Gennari, C. Rationally designed chiral enol borinates powerful reagents for the stereoselective synthesis of natural products. Pure Appl. Chem. 1997, 69, 507-512. 

Ethyl ketones (/ )- and (5)-18 (Scheme 9-8), as introduced by our group, have been u.sed extensively as versatile dipropionate reagents in polyketide synthesis [11]. Selective formation of the (ZO-enol borinate 19 is possible using c-Hex2BCl and the resulting anti aldol products, e.g, 20, are formed with ca. 97% ds [6a]. Several different hydroxyl protecting groups can be accommodated, but benzyl or... 

The completion of the synthesis of ebelactone A required an anti aldol reaction of a suitable three-carbon unit to proceed with and-Felkin selectivity, i.e. a mismatched reaction. Conversion of thioester 280 into its ( )-enol borinate and reaction with aldehyde 279 gave two anti aldol adducts, unfortunately with little stereochemical preference. The minor isomer 281 from this reaction was used in the successful synthesis of ebelactone A (274), and the same chemistry, now using thioester 282, was employed to complete the first synthesis of ebelactone B (275). 

Regiospecific synthesis of Mannich bases. Hooz and Bridson2 have described a new regiospecific3 synthesis of certain Mannich bases which involves first reaction of a trialkylborane with an a-diazoketone in THF to form an enol borinate (l)4 after evolution of nitrogen ceases, dimethyl(methylene)ammonium iodide (2) in DMSO is added. The Mannich base (3) is obtained in 85-100% yield after hydrolytic workup. Cosolvent DMSO is crucial for high yields. 

Our final highlight in the discodermolide synthesis is the use of reagent control to get what we want and not what the molecules want. The combination of enol borinate 276 and an aldehyde 277 featuring a cis double bond, led to the formation of aldols anti- and syn-278. A model study had shown that the inherent selectivity with these enals could be improved by the use of ( )-Ipc groups on boron instead of cyclohexyl but it is not the selectivity that was wanted. (+)-Ipc groups were able to turn around the selectivity and improve the yield of the reaction while they were at it.50... 

The synthesis of rearranged products 28-31 with an anti relationship with respect to the stereocenters at C-2 and C-6 are prepared by starting the reaction sequence with (-Ef-enol borinate aldol reactions via the aldol products 25-27. 

Homolytic cleavage of the carbon-boron bond of a trialkylborane can be promoted by oxygen. The so-formed alkyl radical can be used in synthesis (for radical reactions, see Section 4.1). Indeed, triethylborane in air can be used to generate radicals from precursors such as alkyl iodides or selenides. Hydroboration followed by addition of an a,(3-unsaturated aldehyde or ketone leads to transfer of an alkyl group from the boron atom via an alkyl radical intermediate. The reaction takes place by addition of the alkyl radical to the conjugated system to form an enol borinate, hydrolysis of which gives the aldehyde or ketone product (5.37). 

Non-fluxional vinylic boranes do not react with carbonyl compounds. Nevertheless, the vinylic borane 29 reacts with acetone (2 h under reflux) yielding the Z-isomer of the homoallylic borinic ester 30b. The cw-configuration of the reaction product 30b corresponds to the following sequence of transformations (Scheme 2.11). The [1,7]-H shift in the vinylic borane 29 gives the allylic Z, Z-isomer 28d which immediately reacts with acetone before the equilibrium among the allylic isomers is established. On the other hand, cyclopentanone reacts directly with 29 under mild conditions yielding Z, Z-1,3,5-heptatriene 31 and borinic ester 32 (Scheme 2.12). Apparently 29 reacts with the enol form of cyclopentanone, and a direct splitting of the B-Q ,2 bond takes place. Similar reaction of 29 with acetic acid was used for the preparative synthesis of previously unknown hydrocarbon 31 (Scheme 2.12) [35]. 

Stereoselective Synthesis of (Z)-Enol Borinates from a,p-Unsaturated Ketones... 

Waldmann and coworkers employed the aldol reactions of chiral boron enolates as the key stereoselective transformations toward the solid-phase synthesis of 6,6-spiroketals, a scaffold often found in biologically interesting complex natural products. The polymer-bound aldehyde 1 with a loading of 0.75 mmol/g was treated at —78°C with the preformed (Z)-diisopinocampheyl borinate 2 in dichloromethane for 1.5 h (Scheme 7.1). After storing the reaction mixture at —27°C for 16 h, the resin was filtered and the whole process was repeated once. An oxidative workup followed by TBS protection of the secondary alcohol yielded immobilized s yw-aldol product 3. 

Paterson I, Tillyer RD. High rr-face selectivity in anti aldol reactions of E-enol borinates from chiral alkoxy-methyl ketones stereocontrolled synthesis of a C24—C32 polyol subunit of rapamycin. J. Org. Chem. 1993 58 4182 184. 

Paterson I, Osborne S. Enol borinates in organic synthesis regioselective a-sulphenylation and a-selenylation of ketones. Synlett 1992 145 146. 

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