Aldol Reaction of Boron Enolates

Boron enolates are important intermediates for the aldol reaction, since the transition states of their addition reactions to aldehydes and ketones appear tightly organized, transmitting well the spatial arrangement to the aldol product. The reaction has been reviewed.674,675 

Boryl enolates prepared from A-propionylsultam reacted with aliphatic, aromatic and a,/Tunsaturated aldehydes to provide diastereomerically pure. qw-aldols (Equation (174), whereas the presence of TiCl4 caused complete reversal of the diastereoface selectivity giving anti-aldols (Equation (175)).676-678 Camphor-derived chiral boryl enolates 423 were highly reactive and highly anti-selective enolate synthon system in aldol addition reactions promoted by TiCl4 or SnCl4 co-catalyst (Equation (176)).679 

The Evans-aldol method using a boron enolate derived from chiral iV-acyloxazolidinone reacted with aldehydes to give syn-aldols via attack exclusively on the re face of the double bond of the enolate (Equation (177)). Unexpected and unusual si face attack was resulted in the reaction with fluorine-containing carbonyl compounds such as trifluoro acetaldehyde (Equation (178)).680 681 

Both the nature of solvent and the temperature influenced the stereochemistry of boron enolates, with the solvent effect being greater than that of the temperature. Aliphatic and alicyclic hydrocarbon solvent favored the formation of yy/z-aldols at — 78 °C, whereas aromatic and chlorinated aliphatic solvents favored the formation of anti-dXdoh at 0-25 °C (Equation (179)).682 683 

The stereochemical course of the aldol reaction can be controlled by the judicious selection of the enolization reagents. Treatment of propionate esters with 7-Hex2BOTf and triethylamine produced anti-aldol products, and that of with Bu2BOTf and diisopropylethylamine selectively gave syn-aldol products after reaction with aldehydes (Equation (180)).684 685 Complementary anti- and yy/z-selective asymmetric aldol reactions were also demonstrated in structurally related chiral norephedrine-derived propionate esters (Equation (181)).686 

---

Bernard A, A M CapeUi, A Comotti, C Gannari, J M Goodman and I Paterson 1990. Transltion-St Modeling of the Aldol Reaction of Boron Enolates A Force Field Approach. Journal of Orga Chemistry 55 3576-3581. 

Aldol Reactions of Boron Enolates. The matter of increasing stereoselectivity in the addition step can be addressed by using other reactants. One important version of the aldol reaction involves the use of boron enolates.15 A cyclic TS similar to that for lithium enolates is involved, and the same relationship exists between enolate configuration and product stereochemistry. In general, the stereoselectivity is higher than for lithium enolates. The O-B bond distances are shorter than for lithium enolates, and this leads to a more compact structure for the TS and magnifies the steric interactions that control stereoselectivity. 

Aldol reactions of boron enolates are frequently more diastereoselective than aldol reactions of, for example, lithium or aluminium enolates. This is partly ascribed to the relatively short boron-oxygen bond length (B-O = 1.36-1.47 A, Li-0 = 1.92-2.00 A, Al-0 = 1.92 A) which exacerbates the unfavourable 1,3-diaxial interactions that occur between the boron substituent... 

Bernard , A., Capelli, A. M., Gennari, C., Goodman, J. M., Paterson, I. Transition-state modeling of the aldol reaction of boron enolates a... 

Table 4 Aldol Reactions of Boron Enolates Derived from Enantiomerically Pure Acyl Sultam (58) ...

Spiroketals have been obtained by RCM of cyclic ketals 18 without loss of stereochemical integrity at the spiro linkage <04TL5505> and a stereoselective solid-phase synthesis of 6,6-spiroketals has been reported in which aldol reactions of boron enolates are the key feature <04AG(E)3195>. Spiro orthoesters are accessible from thiophenyl ketene acetals and diols (Scheme 5) <04SL2013>. 

The synthesis of three fragments 278, 282, and 285 for the C21-C42 bottom segment is summarized in Scheme 41. The Eschenmoser-Claisen rearrangement of amido acetal of 276, which was prepared via 2-bromocyclohexenone by Corey s asymmetric reduction, afforded amide 277. Functional group manipulation including chain elongation provided Evans-type amide 278. The Evans aldol reaction of boron enolate of 279 with aldehyde 280 stereoselectively afforded 281, which was converted into aldehyde 282 through a sequence of seven steps... 

Aldol Reactions. - Seebach et al. have published a detailed study of the diasteroselective aldol reaction of boron enolates, generated from an ethyl ketone by treatment with boron trichloride or an alkoxydichloroborane in the presence of Hunig s base. The reaction was found to occur with ul topicity in selectivities from 90-99%... 

Preparation of the left-hand fragment, which incorporates the C-11 to C-13 portion of 18, utilizes the aldol reaction of / -boron enolate 10 with propionaldehyde to provide the a-hydroxy acid 11 in 85% yield and 100 1 stereoselectivity. Subsequent diazomethane esterification, O-silylations, DIBAL reduction, and Collins oxidation affords the optically pure aldehyde 12 in an overall yield of 75%. 

There have been several recent solid-phase and solution-phase libraries reported that contain the spiroketal moiety (Figure 7.5). These libraries introduce additional structural complexity and new interaction modes of carbohydrate-like molecules with biological targets. Ley and cowoikers reported the solid-supported synthesis of spiroketals. Using stereoselective aldol reactions of boron enolates, the Waldmann and Paterson groups reported the solid-phase synthesis of 6,6-spiioketals. The 1,7-dioxaspiro [5.5]undecane spiroketal served as the core template for Porco s three-point diversity library to explore protein-protein interactions. ... 

Subsequent aldol reactions of boron enolates vith aldehydes proceed vithout loss of regiochemical integrity, but the reactions vith ketones proceed slo vly and the regiochemical integrity of an aldol product does not reflect that of an enolate. 

---