Asymmetric Aldol Reactions Using Boron Enolates

Abstract

The directed aldol reaction allows the construction of new carbon–carbon bonds in a regio‐, diastereo‐, and enantioselective manner. The kinetically controlled, boron‐mediated aldol reaction is particularly powerful for the efficient synthesis of β‐hydroxy carbonyl compounds. Compared to other metal enolates, the boron–oxygen bond in boron enolates is relatively short which, on addition to aldehydes, leads to tight cyclic transition states and highly stereoselective carbon–carbon bond formation. Moreover, variation of the steric demands of the ligands on boron allows discrimination between competing transition states. Chiral auxiliaries attached to the boron enolate are frequently employed to control the relative and absolute stereochemistry of the aldol products. Asymmetric reactions using chiral ligands on boron are also possible and these produce useful enantiomerically enriched adducts. The utility of boron‐mediated aldol reactions has been demonstrated in numerous total syntheses of complex polyoxygenated natural products, and several of these are highlighted in the Application to Synthesis section of this chapter. Several reviews of the directed aldol reaction are available, including the Organic Reactions chapter by Mukaiyama in 1981. 9 The material covered in this review concerns only the asymmetric formation of β‐hydroxy carbonyl compounds using boron enolates and surveys the literature from 1981 until the end of 1995.

On the Origin of Siphonariid Polypropionates: Total Synthesis of Caloundrin B and Its Isomerization to Siphonarin B

“…The relative topicity of the reaction agreed with the reports in the literature for the diastereoselectivity observed from (Z)-enolates in acyclic systems. 66 However, the Felkin aldehyde diastereoface selectivity observed was opposite to the generally expected results in aldol reactions of chiral Z-enolates and chiral 2-Me aldehydes (i.e. 10,12-anti-12,13-syn-13,14-anti).…”

Synthesis and Biological Evaluation As Microtubule-Active Agents of Several Tetrahydrofuran and Spiroacetal Derivatives

“…The aldol reaction of aldehyde 16 with the boron enolate [32] of ketone 13, generated with the aid of di-n-butylboron triflate, provided an inseparable mixture of aldol 17 and its epimer 18 at the hydroxyl-bearing carbon atom (diastereoisomeric ratio about 66:34) [33,34]. Treatment of the mixture of epimers with aqueous HF caused cleavage of the SEM and TBS groups, followed by spiroacetalization [22], to afford 6 and 8, which were separated.…”

Synthesis of antimicrofilament marine macrolides: Synthesis and configurational assignment of a C 5 –C 16 degradation fragment of reidispongiolide A

“…The synthesis of the (7S) C 5 -C 16 fragment is detailed in Scheme 10. By following our standard conditions (20), the aldol coupling between 45 and 48 with (Ϫ)-Ipc 2 BCl͞Et 3 N afforded the desired ␤-hydroxyketone 52 as the major adduct. § In this case, the inherent 1,5-anti-selectivity observed in the coupling of ent-45 and 48 (Scheme 9) was overturned by appropriate choice of Ipc ligand chirality.…”