Of enol borinates

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... 

In diastereo- and enantiocontrolled aldol addition, the use of enol borinates or enol stannanes has emerged as a standard methodology (Evans or Oppolzer aldol addition) [105]. These intermediates are generated in situ from the parent carbonyl compounds, which typically are auxiliary-substituted amides or esters. The counter ion, which is attached to the enolate, plays a dominant role in the stereochemical outcome. 

By employing optically active enol borinates instead of silylketene acetals, the Ireland-Claisen rearrangement has been further developed to an enantioselective... 

The enol acetates, in turn, can be prepared by treatment of the parent ketone with an appropriate reagent. Such treatment generally gives a mixture of the two enol acetates in which one or the other predominates, depending on the reagent. The mixtures are easily separable. An alternate procedure involves conversion of a silyl enol ether (see 12-22) or a dialkylboron enol ether (an enol borinate, see p. 560) to the corresponding enolate ion. If the less hindered enolate ion is desired (e.g., 126), it can be prepared directly from the ketone by treatment with lithium diisopropylamide in THE or 1,2-dimethoxyethane at —78°C. ... 

Regioselectivity in the halogenation of unsymmetrical ketones can be attained by treatment of the appropriate enol borinate of the ketone with NBS or NCS. The desired halo ketone is formed in high yield. Another method for achieving the... 

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. ... 

For conversion of ketones to either (Z) or ( ) enol borinates, see, for example, Evans,... 

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. 

E)- or (Z)-Enol borinates. These ends are useful for stereoselective preparation of anti- or jyn-aldols, respectively, and have usually been obtained stereoselec-tively by variation of the alkyl group attached to boron triflates. They can also be prepared in essentially quantitative yield by reaction with dialkylboron chlorides at... 

To achieve a stereoselective aldol reaction that does not depend on the structural type of the reacting carbonyl compounds, many efforts have been made to use boron enolates. Based on early studies by Mukaiyama et al.8a and Fenzl and K0ster,8b in 1979, Masamune and others reported a highly diastereoselective aldol reaction involving dialkylboron enolates (enol borinates)9... 

Gennari et al. developed a computational model to reproduce the experimental syn/anti setereoselectivity for the aldol reactions of Z and E enol borinates of butanone with acetaldehyde.13 For the reaction of Z-enol borinate 8Z, the chair transition state TS Z-chair A dominates over other three-transition states (Scheme 2.XI). When a Boltzmann distribution was calculated for the competing transition structures, a complete syn/anti selectivity of 99 1 was predicted. The aldol reaction of E-enol borinate 8E with acetaldehyde is, however, calculated to have four transition structures of similar energy (Scheme 2.XII). Although... 

Masamune et al. applied the newly developed enantioselective anti-aldol reaction to the syntheses of two key fragments of miyakolide 5, a bryostatin-like marine metabolite5 (Scheme 2.2e). The readily synthesized aldehyde 8 was treated with chiral enol borinate generated from the ester 3 to give the aldol 9 in 85%... 

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%). 

---