Cyclohexyl boronate

When 4-bromobenzaldehyde is allowed to react with n-butyl(cyclohexyl)boron chloride, the major product is cyclohexyl(4-bromophenyl)methanol (Scheme 23.58). 

A more eflicient and general synthetic procedure is the Masamune reaction of aldehydes with boron enolates of chiral a-silyloxy ketones. A double asymmetric induction generates two new chiral centres with enantioselectivities > 99%. It is again explained by a chair-like six-centre transition state. The repulsive interactions of the bulky cyclohexyl group with the vinylic hydrogen and the boron ligands dictate the approach of the enolate to the aldehyde (S. Masamune, 1981 A). The fi-hydroxy-x-methyl ketones obtained are pure threo products (threo = threose- or threonine-like Fischer formula also termed syn" = planar zig-zag chain with substituents on one side), and the reaction has successfully been applied to macrolide syntheses (S. Masamune, 1981 B). Optically pure threo (= syn") 8-hydroxy-a-methyl carboxylic acids are obtained by desilylation and periodate oxidation (S. Masamune, 1981 A). Chiral 0-((S)-trans-2,5-dimethyl-l-borolanyl) ketene thioketals giving pure erythro (= anti ) diastereomers have also been developed by S. Masamune (1986). 

The reaction between 5-methyl-2-(l-methyl-1 -phenylethyl)cyclohexyl 2-oxoacetate and 2-buteny](tributyl)stannane promoted by boron trifluoride-diethyl ether complex showed a strong preference for 57-facial attack, with syn selectivity69. 

In contrast, highly stereoselective aldol reactions are feasible when the boron etiolates of the mandelic acid derived ketones (/ )- and (5,)-l- t,r -butyldimethylsiloxy-l-cyclohexyl-2-butanone react with aldehydes33. When these ketones are treated with dialkylboryl triflate, there is exclusive formation of the (Z)-enolates. Subsequent addition to aldehydes leads to the formation of the iyn-adducts whose ratio is 100 1 in optimized cases. 

If a chiral aldehyde, e.g., methyl (27 ,4S)-4-formyl-2-methylpentanoate (syn-1) is attacked by an achiral enolate (see Section 1.3.4.3.1.), the induced stereoselectivity is directed by the aldehyde ( inherent aldehyde selectivity ). Predictions of the stereochemical outcome are possible (at least for 1,2- and 1,3-induction) based on the Cram—Felkin Anh model or Cram s cyclic model (see Sections 1.3.4.3.1. and 1.3.4.3.2.). If, however, the enantiomerically pure aldehyde 1 is allowed to react with both enantiomers of the boron enolate l-rerr-butyldimethylsilyloxy-2-dibutylboranyloxy-1-cyclohexyl-2-butene (2), it must be expected that the diastereofacial selec-tivitics of the aldehyde and enolate will be consonant in one of the combinations ( matched pair 29), but will be dissonant in the other combination ( mismatched pair 29). This would lead to different ratios of the adducts 3a/3b and 4a/4b. 

IS, 2/ )-l-Cyclohexyl-2-methyl-3-buten-l-ol [Representative Procedure for Additions of ( )-Crotyl Diisopropyl Tartrate Boronate to Aldehydes]. ... 

Alkenylboronic acids and esters have been prepared by thermal or catalyzed hydroboration of 1-alkynes with catecholborane (HBcat), pinacolborane (HBpin), or dihaloboranes 41-43, followed by hydrolysis to boronic acids or alcoholysis to boronic esters. A convenient alternative to improve chemo- and regioselectivity is the hydroboration of alkynes with dialkylboranes. For selective removal of dummy groups, the oxidation of two cyclohexyl groups was conduced by treatment of l-alkenyl(dicyclohexyl)borane intermediates with Me3N-0 (Equation (7)).116 The... 

The situation is similar with cyclic boronates, which are prepared by the following procedure. Steroid (10 pmol) and the respective substituted boric acid (10 jumol) are dissolved in ethyl acetate (1 ml) and the mixture is allowed to stand for 5 min at room temperature. Under these conditions, 17,20-diols, 20,21-diols and 17,20,21-triols are converted completely into boronates. Cyclic boronate was mainly produced from 17,21-dihydroxy-20-ketone, but side-products also appeared, the formation of which could be suppressed by adding a 10% excess of the reagent [387—389]. Different substituents on the boron atom, such as methyl, n-butyl, tert.-butyl, cyclohexyl and phenyl, are interesting from the viewpoint of GC—MS application. They are further suitable for converting isolated hydroxyl groups into TMS or acetyl derivatives. 

If the intermediates are treated with mercury(II) chloride to induce a second migration from boron to carbon and then oxidized, tertiary alcohols can be obtained. The very hindered cyclohexyldicyclopentylcarbinol was prepared in this way in 80% yield from 1 (R = cyclohexyl) and dicyclopentylhexylborane. ... 

Moderate to high diastereoselectivities are also obtained in the hydroboration of oxygen- and boron-substituted homoallylic bicyclohexyl derivatives35- 38. These reactions are selective for the products with erythro linkages between the cyclohexyl rings. 

The products (6) are very prone to hydrolytic cleavage by base this is presumably due to the ready production of an intermediate carbanion followed by its rapid protonation. This possibility was tested by treating a series of compounds (6 R = cyclohexyl) with Bu"Li at -78 C in THF. The products had properties consistent with the production of (7 equation 2). The by-product, a simple trialkylborane, also reacts with butyllithium, and so 2 equiv. of the latter must be add. Thus, the process is wasteful in that one atom of boron and 1 equiv. of base are consumed in an unproductive fashion (equation 3). 

The photostadDility of boron-containing orgamic complexes has been discussed, amd a study maule of the luminescent properties of p-diketonates of disubstituted boron amd of bis-p-diketonatoboron. A novel photochemical alkyl migration from B to C in the dialkyIboryl acetylacetonate complexes (1) ( R-cyclohexyl, Bu, isopinocaunpheyl, R -H R-cyclohexyl, Bu, R -Me ) has appeared. Crossover experiments show that the alkyl migration is essentially intraunolecular Silicon... 

Cyclohexylbenzene has been prepared by the hydrogenation of biphenyl and of cyclohexenylbenzene over nickel, by the reaction of cyclohexyl chloride or bromide with benzene in the presence of aluminum chloride, and by the addition of benzene to cyclohexene in the presence of aluminum chloride, sulfuric acid, or boron halides. ... 

---