Asymmetric synthesis of a 3,4-substituted pyrrolidine by l-proline catalyzed direct enolexo aldolization

The asymmetric synthesis of a 3,4-substituted N-tosyl pyrrolidine has been achieved by using l-proline catalyzed 5-enolexo aldolization with high enantio and diastereoselectivity.

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Benzyl {[(4S)-2,2-dimethyl-1,3-dioxolan-4-yl]methyl}(3-hydroxypropyl)carbamateC17H25NO5[α]D25=-7.6 (c 1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (4S)

Benzyl (2S)-3-acetoxy-2-hydroxypropyl-3-acetoxypropylcarbamateC18H25NO7[α]D25=-5.0 (c 1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2S)

Benzyl (2S)-3-acetoxy-2-tert-butyldimethylsilyloxypropyl-3-acetoxypropylcarbamateC24H39NO7Si[α]D25=-9.2 (c 1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2S)

(5S)-5-tert-Butyldimethylsilyloxy-3-(3-hydroxypropyl)-1,3-oxazinan-2-oneC13H27NO4Si[α]D25=-5.3 (c 1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (5S)

{[(2S)-3-Acetoxy-2-tert-butyldimethylsilyloxypropyl](benzyl)amino}propylacetateC23H39NO5Si[α]D25=-12.2 (c 1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2S)

(2S)-2-tert-Butyldimethylsilyloxy-3-[benzyl(3-hydroxypropyl)amino]propanolC19H25NO3Si[α]D25=-13.4 (c 1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2S)

N-{[(4S)-2,2-Dimethyl-1,3-dioxolan-4-yl]methyl}-N-(3-hydroxypropyl)-4-methylbenzenesulfonamideC16H25NO5S[α]D25=-11.0 (c 1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (4S)

(2S)-3-Acetoxy-2-tert-butyldimethylsilyloxypropyl-N-(3-acetoxypropyl)-4-methylbenzenesulfonamideC23H39NO7SSi[α]D25=+5.25 (c 1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2S)

(2S)-2-Hydroxy-3-tert-butyldimethylsilyloxypropyl-N-(hydroxypropyl)-4-methylbenzenesulfonamideC19H35NO5SSi[α]D25=-7.5 (c 1, CHCl3)Source of chirality: d-mannitolAbsolute configuration: (2S)

(3R,4S)-3-Hydroxy-4-(hydroxymethyl)-N-[4-methylphenylsulfonyl]pyrrolidin-3-yl-methyl-tert-butyldimethylsilyletherC19H33NO5SSi[α]D25=-5.1 (c 0.5, MeOH)Source of chirality: l-proline catalyzed aldol reactionAbsolute configuration: (3R,4S)

(3R,4S)-3,4-Bis(hydroxymethyl)-1-[(4-methylphenyl)sulfonyl]pyrrolidin-3-olC13H19NO5S[α]D25=-3.9 (c 1, MeOH)Source of chirality: l-proline catalyzed aldol reactionAbsolute configuration: (3R,4S)

{(3R,4S)-3-Hydroxy-N-[4-(methylphenyl)sulfonyl]pyrrolidine-3,4-diyl}bis(methylene)diacetateC17H23NO7S[α]D20=+2.9 (c 0.5, CHCl3)Source of chirality: l-proline catalyzed aldol reactionAbsolute configuration: (3R,4S)