Diastereoselective Aldol Reactions of Furaldehyde Using a Chiral Boronate as Auxiliary: Application to the Synthesis of Enantiomerically Pure and Highly Functionalized 2,3-Disubstituted Furanyl Alcohols

Abstract

The aldol reactions of various ketene silyl acetals or lithium enolates with furaldehyde 2, which bears a chiral boronate group at the furan C‐3 position, as auxiliary have been studied. It was found that (R) diastereoselectivity was more favorable than (S) diastereoselectivity and moderate diastereoselectivity was achieved. Some of the resulting aldol diastereomers were chromatographically separable by simple flash column chromatography on silica gel, leading to optically pure aldol adducts. The absolute stereochemistry of the aldol adducts were determined by X‐ray crystallographic analysis. Further transformation of the carbon−boron bond to a carbon−carbon bond was achieved in a Suzuki coupling reaction to furnish highly functionalized and enantiomerically pure 2,3‐disubstituted furyl alcohols. One of the furyl alcohols was allowed to rearrange to hydroxypyranone in order to demonstrate the usefulness of this methodology. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Diastereoselective Addition Reactions of Furyl Sulfonylimine Using Chiral Boronates as Auxiliary: Application to the Enantioselective Synthesis of 2,3-Disubstituted Furyl Sulfonylamides

“…In earlier work, we disclosed that for the addition reactions to furyl aldehyde 3 , the Re -face attack of nucleophiles to the carbonyl group of 3 was found to be more favorable 7a. This result was consistent with information being obtained from both X-ray crystallography (solid state) and AM1 calculations (solution state) .…”

“…The boronic ester of (2 R ,3 R )-1,4-dimethoxy-1,1,4,4-tetraphenyl-2,3-butanediol ( 2 ) has been used as an efficient chiral auxiliary in asymmetric synthesis . Moreover, in our earlier work, we have successfully employed a similar strategy to synthesize various optically active 2,3-disubstituted furyl alcohols from furyl aldehyde 3 with high diastereoselectivities . In connection with our interest in the realization of highly functionalized dihydropyridone 1 , we herewith wish to report our employment of boronic ester as chiral auxiliary for the synthesis of optically pure 2,3-disubstituted furylamines.…”

Metalated Heterocycles and Their Applications in Synthetic Organic Chemistry

“…Zinc borates of this type have also been employed . On the other hand, a furaldehyde bearing a chiral boronate group at the furan C-3-position has been used in diastereoselective additions 281 and aldol reactions 55 …”

Direct Palladium-Catalyzed Alkynylation of N-Fused Heterocycles

“…It is well-established that species i serve as key electrophilic intermediates in Pd-catalyzed arylation/vinylation of electron-rich heterocycles . It is also known that the similar intermediate v , which forms upon oxidative addition of palladium into alkynylhalides, effectively serves as an electrophilic component in Stille and Suzuki cross-coupling reactions with the corresponding stannyl- and boryl- heterocycles. We hypothesized that, analogously to i , electrophilic species v may also undergo reaction with nonfunctionalized electron-rich heterocycles …”