Recyclable supports for stereoselective 1,3-dipolar cycloadditions: application of a fluorous oxazolidinone chiral auxiliary

The utility of a new fluorous-supported chiral auxiliary was tested using a series of catalyzed and uncatalyzed 1,3-dipolar cycloaddition reactions with diphenylnitrone. The yields and selectivities of the cycloadducts compare favourably with those obtained using the conventional Evans-type auxiliaries, while purification was greatly assisted by using fluorous solid phase extraction. Following characterization, the cycloadducts were released from the auxiliaries by reductive cleavage. The auxiliary was readily refunctionalized and reused in subsequent cycloaddition reactions, with no deterioration of the observed yields or selectivities.

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(4S,5R)-4-Benzyl-5-(1′H,1′H,2′H,2′H-perfluorooctyl)-oxazolidin-2-oneC18H14F13NO2Ee = 98%[α]D25=-30.0 (c 1.0, CHCl3)Source of chirality: chiral pool starting materialAbsolute configuration: (4S,5R)

(E)-(4S,5R)-4-Benzyl-3-(2′-butenoyl)-5-(1′H,1′H,2′H,2′H-perfluorooctyl)-2-oxazolidinoneC22H18F13NO3Ee = 98%[α]D25=+13.4 (c 1.0, CHCl3)Source of chirality: chiral pool starting materialAbsolute configuration: (4S,5R)

(3′R,4S,4′S,5R,5′R)-4-Benzyl-3-((5′-methyl-2′,3′-diphenylisoxazolidin-4′-yl)carbonyl)-5-(1′H,1′H,2′H,2′H-perfluorooctyl)-2-oxazolidinoneC35H29F13N2O4Ee = 98%[α]D25=+99.1 (c 0.8, Et2O)Source of chirality: asymmetric synthesisAbsolute configuration: (3′R,4S,4′S,5R,5′R)

(3′S,4S,4′R,5R,5′S)-4-Benzyl-3-((5′-methyl-2′,3′-diphenylisoxazolidin-4′-yl)carbonyl)-5-(1′H,1′H,2′H,2′H-perfluorooctyl)-2-oxazolidinoneC35H29F13N2O4Ee = 98%[α]D25=+32.8 (c 0.5, Et2O)Source of chirality: asymmetric synthesisAbsolute configuration: (3′S,4S,4′R,5R,5′S)

(3′S,4S,4′S,5R,5′R)-4-Benzyl-3-((5′-methyl-2′,3′-diphenylisoxazolidin-4′-yl)carbonyl)-5-(1′H,1′H,2′H,2′H-perfluorooctyl)-2-oxazolidinoneC35H29F13N2O4Ee = 98%[α]D25=+88.5 (c 0.5, Et2O)Source of chirality: asymmetric synthesisAbsolute configuration: (3′S,4S,4′S,5R,5′R)

(3′R,4S,4′R,5R,5′S)-4-Benzyl-3-((5′-methyl-2′,3′-diphenylisoxazolidin-4′-yl)carbonyl)-5-(1′H,1′H,2′H,2′H-perfluorooctyl)-2-oxazolidinoneC35H29F13N2O4Ee = 98%[α]D25=+27.4 (c 0.32, Et2O)Source of chirality: asymmetric synthesisAbsolute configuration: (3′R,4S,4′R,5R,5′S)