Oxazoline boron azaenolates

Boron triflates 45a and 45b are very useful chiral auxiliaries. Boron azaenolate derived from achiral35 and chiral36 oxazolines gives good stereoselectivity in the synthesis of acyclic aldol products, particularly for the rarely reached threo-isomers. By changing the chiral auxiliary, the stereochemistry of the reaction can be altered.37... 

Boron Azaenolates from Oxazolines. The reagent is useful for asymmetric aldol condensations of achiral oxazolines. Treatment of 2-ethyl-4-dimethyl-2-oxazoline with IpC2BOTf in the presence of a tertiary amine furnishes a boron azaenolate. Without isolation, treatment with an aldehyde in ether at —78 °C provides an alkylated oxazoline, which is hydrolyzed and converted to p-hydroxy ester via treatment with Diazomethane. Although the yields for the four-step sequence are only moderate, the anti selectivities of the hydroxy acids are excellent with enantioselec-tivities of 77-85% ee (eq 1). ... 

Asymmetric Aldol Additions. 2-Ethyl-2-oxazoline takes part in aldol condensations as its boron azaenolate. The erythro selectivity for this protocol is excellent (95 5 to 98 2) but the enantios-electivity is only moderate (29-71% ee eq 6). ... 

Boron azaenolates derived from chiral oxazolines have been reacted with aldehydes [154, 697], and anti aldols are formed with high diastereoselectivity (> 95%) but with modest enantiomeric excess. More satisfactory results were obtained by Narasaka and Niwa [1277] by using tin azaenolate 6.102 (Figure 6.85). 

Meyers et al reported the use of boron azaenolate (53), derived from enantiomerically homogeneous oxazoline (54) and 9-BBN triflate, for the preparation of 2,3-syn aldol units (55), as shown in Scheme 28. The resulting jyn-3-hydroxy-2-methyl esters (56) are obtained with very high (95-98%) syn dia-stereoselectivities but modest enantiomeric excesses (29-71 % ee). 

In 1981 Meyers and Yamamoto reported the use of an external reagent in the construction of a 2,3-anti unit. The boron azaenolate (85), prepared from the chiral boron reagent (86 diisopinocampheylbotyl triflate lpc2BOTf) and the achiral oxazoline derivative (87), reacts with aldehydes in ether at -78 C (Scheme 36). The direct products (88) are converted, after hydrolysis and esterification, to the corresponding a-methyl-P-hydroxycarboxyl derivatives (89), which are rich in the anti isomer (antiisyn... 

By judicious choice of chiral auxiliary-reagent pairs, it has been possible to extend this chemistry to the enantioselective synthesis of p-hydroxy-a-methyl-carboxylic acid derivatives having either anti or syn stereochemistry (Schemes 24 and 25). For example, the boron azaenolate obtained upon reaction of (65) with diisopinocamphenylboryl triflate reacts with a series of aldehydes to provide adducts that are readily converted to the anti methyl esters (66) in good overall yields (Scheme 24). The anti.syn ratios for these reactions are typically >9 1, and the percentage enantiomeric excesses for the anti adducts are in the range of 77-85%. On the other hand, the boron azaenolate derived from oxazoline (61c) and 9-borabicyclononane triflate reacts with aldehydes to give adducts that can be converted into the methyl esters of the jyn-carboxylic acids (67 Scheme 25). The symanti ratios in these reactions are typically... 

The boron azaenolate with an oxazoline ring as the chiral auxiliary unit undergoes condensation [13] with aldehydes to give mainly erythro- -hydroxy esters (Eq. 6.26). The reaction proceeds with high diastereoselection, but enanti-oselection is moderate. 

Enantioselective aldol reactions with high threo- or erythro-scleciivity are obtained with boron azaenolates derived from chiral and achiral oxazolines, respectively. Moving the chirality from the boron in (50), to the heterocyclic in (51), causes the reaction to switch from threo- to eryt/iro-products with high... 

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