Chiral oxazaborolidinones

Asymmetric aldol reaction promoted by chiral oxazaborolidinone 97YGK313. 

The polymer-supported chiral oxazaborolidinone catalyst 5 prepared from valine was found by Ituno and coworkers to be a practical catalyst of the asymmetric Diels-Alder reaction [7] (Scheme 1.12). Of the several cross-linked polymers with a... 

A valine-based chiral oxazaborolidinone 80 (generated in situ from Ts-L-Val and BH3-THF) was used by Kiyooka and co-workers [37] to catalyse the reaction be-... 

Figure 39 The enantioselective polymer-supported catalysts (61) of chiral oxazaborolidinone with cross-linking structures for use in the Diels-Alder reaction of methacrolein with cyclopentadiene. (Adapted from ref. 85.)...

Asymmetric aldol reactions promoted by chiral oxazaborolidinones can achieve high ee with critical quantities of THF, typically a 4-5-fold excess over the borane.117 Ah initio calculations on Lewis acid-aldehyde-solvent complexes have been used to rationalize such results extended hydrogen bonding networks have been identified. 

The same reaction has also been catalyzed by chiral oxazaborolidinones derived from amino acids and boranes. They proved to be efficient catalysts for enantioselec-tive Diels-Alder reaction [91,92]. The polymer-supported chiral oxazaborolidinones 75 were reported to be efficient catalysts [93]. These polymer-supported chiral oxaza-borolidinone ligands were prepared both by chemical modification and by the copolymerization shown in Sch. 5 [94]. The polymer-supported chiral ligands were then reacted with borane to give the oxazaborolidines which were used as catalysts in Diels-Alder reaction of cyclopentadiene with methacrolein. 

Chiral oxazaborolidinones supported on silica gel 77 have been prepared as shown in Sch. 6 [87]. Although high conversion was attained with these catalysts, enantioselectivity was low (8 % ee). 

Prolinol derivatives of boron tribromide 4 give excellent results in the [4 + 2] cycloaddition of methacrolein (8a) to cyclopentadiene (exojendo ratio 99 1, 97% ee)21. Several boron catalysts derived from /V-sulfonamides of a-amino acids 7a-d have been developed. In the cycloaddition of methacrolein (8a) or croton aldehyde (8b) to cyclopentadiene these catalysts produce enan-tioselectivities ranging from medium to good8-22 23. Chiral oxazaborolidinone 6 is an excellent catalyst for the addition of 2-bromoacrolein (8e) to various dienes24 (see table overleaf)-... 

Most recent research has been focused on the application of polymers as chiral auxiliaries in enantioselective Lewis-acid-catalyzed reactions. Studies of Itsuno and co-workers [44] culminated in the development of a polymer-supported catalyst containing a chiral oxazaborolidinone with oxyethylene crosslinkages which gave the Diels-Alder adduct of cyclopentadiene and methacrolein in 88 % isolated yield with an exotendo ratio of 96 4 and 95 % e. e. for the exo adduct. A variety of polymer-supported chiral Lewis acids was also investigated by Mayoral et al. [45]. Some supported catalysts were more active than their homogeneous analogs, but enantioselectivity was always lower. 

A variety of solid Lewis and Br0nsted acids has been shown to catalyze Diels-Alder reactions. In several instances the results obtained with heterogeneous catalysts were better than those with homogeneous Lewis acid catalysts. Most of the reported reactions of interest in the synthesis of fine chemicals were catalyzed by (modified) zeolites, clays, alumina, or silica. Catalysts with interesting properties were obtained when support materials such as zeolites, alumina, or silica were treated with Lewis acids. These catalysts were moderately selective in diastereo-selective Diels-Alder reactions with chiral dienophiles and induced enantioselec-tivity (up to 31 % e. e.) in the reaction of cyclopentadiene with methacrolein after treatment with chiral derivatives. Excellent enantioselectivity in this reaction (up to 95 % e. e.) was observed with a polymer-supported chiral oxazaborolidinone. Because of their facile recovery and recycling, we expect that solid-acid catalysts will find increasing use in Diels-Alder reactions in the future. 

As a stronger Br0nsted acid, chiral binaphthol-based phosphoric acid 8 and /V-triflyl phosphoramide 9 were recently introduced to the FCA reaction of enones. Reports by a few groups on the alkylations of indoles showed that simple enones were still challenging substrates, and modest ee values were recorded with a few examples over 90% ee (Scheme 9.8) [23]. However, excellent enantioselectivities were achieved in the intramolecular C3 and N1 alkylations of indole by You and co-workers (Scheme 9.9) [24]. Noteworthy, chiral oxazaborolidinone and... 

A vinylogous Mukaiyama of an aldehyde with an aldehyde-derived dienolate gives access to a-substituted S-hydroxy-a./S-unsaturated aldehydes in up to 94% ee, using chiral oxazaborolidinone catalysts. ... 

An optically active polymer has been prepared by repetitive Mukaiyama aldol reaction, using a bis(silyl ketene acetal) and a dialdehyde, plus a chiral oxazaborolidinone catalyst,and the role of Lewis basicity of aldehydes in oxazaborolidinone-catalysed Mukaiyama aldols has been examined." ... 

Masamune and coworkers developed an enantioselective Mukaiyama aldol protocol that is based upon chiral oxazaborolidinones like 183 that are generated from BHj THF and the /lara-toluenesulfonamide of the corresponding a-amino acid. Mediated by 20 mol% of the chiral additive, the reaction of the silyl ketene... 

Chiral oxazaborolidinones (20, 22, Scheme 2.127) can also promote Mukaiyama reactions and VMARs. It should be pointed out that the substitution on boron significantly alters the face selectivity of this process. If the boron atom is additionally substituted by alkyl groups (20), both this aUcyl group and the residues on the amino acid adopt an anh-orientation. If the substituent is just hydrogen (22), then this becomes a iy -orientation and ultimately the face selectivity is altered. 

Hena, M.A., Kim, C.S., Horiike, M., and Kiyooka, S. (1999) Toward a practical synthesis of acutiphycin. Highly stereoselective synthesis of ClO-epi seco acid derivative via reaction paths shortened by using a series of chiral oxazaborolidinone-promoted aldol reactions. Tetrahedron Lett., 40, 1161-1164. 

Kiyooka, S. and Maeda, H. (1997) Enantioselective acyclic stereoselection under catalyst control. III. A very short asymmetric synthesis of the bryostatin C1-C9 segment using the chiral oxazaborolidinone-promoted aldol reaction. Tetrahedron Asymmetry,... 

---