A common approach to pyrrolizidine and indolizidine alkaloids; formal synthesis of (−)-isoretronecanol, (−)-trachelanthamidine and an approach to the synthesis of (−)-5-epitashiromine and (−)-tashiromine

A common and short stereoselective route is described for the formal synthesis of pyrrolizidine alkaloids, (−)-isoretronecanol and (−)-trachelanthamidine. An approach to the synthesis of indolizidine alkaloids (−)-5-epitashiromine and (−)-tashiromine utilizing ring closing metathesis is also described starting from commercially available and inexpensive l-proline.

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(S)-tert-Butyl 2-(hydroxymethyl)pyrrolidine-1-carboxylateC10H19NO3[α]D25=-39.75 (c 1.2, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (S)

(S)-tert-Butyl 2-vinylpyrrolidine-1-carboxylateC11H19NO2[α]D25=-11.5 (c 1.0, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (S)

(S)-tert-Butyl 2-((R)-1,2-dihydroxyethyl)pyrrolidine-1-carboxylateC11H21NO4[α]D25=-38.3 (c 1.8, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (S,2R)

(S)-tert-Butyl 2-((R)-1-(benzyloxy)-2-hydroxyethyl)pyrrolidine-1-carboxylateC18H27NO4[α]D25=-29.4 (c 1.4, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (S,2R)

(S)-tert-Butyl 2-(2-hydroxyacetyl)pyrrolidine-1-carboxylateC18H25NO4[α]D25=-34.5 (c 1.0, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (S)

(S)-tert-Butyl 2-(3-hydroxyprop-1-en-2-yl)pyrrolidine-1-carboxylateC19H21NO3[α]D25=-30.3 (c 1.0, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (S)

(S)-1-(2-(3-(Benzyloxy)prop-1-en-2-yl)pyrrolidin-1 -yl)prop-2-en-1-oneC17H21NO2[α]D25=-8.7 (c 1.2, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (S)

(S)-1-(Benzyloxymethyl)-5,6,7,7a-tetrahydropyrrolizin-3-oneC15H17NO2[α]D25=-40.8 (c 1.1, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (S)

((1S,7aS)-3-Oxo-hexahydro-1H-pyrrolizin-1-yl)methyl benzoateC15H17NO3[α]D25=-30.8 (c 1.5, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (1S,7aS)

((1R,7aS)-3-Oxo-hexahydro-1H-pyrrolizin-1-yl)methyl benzoateC15H17NO3[α]D25=-11.7 (c 1.0, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (1R,7aS)

(1S,7aS)-1-(Hydroxymethyl)-hexahydropyrrolizin-3-oneC8H13NO2[α]D25=-64.5 (c 1.0, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (1S,7aS)

(1R,7aS)-l-(Hydroxymethyl)-hexahydropyrrolizin-3-oneC8H13NO2[α]D25=+15.5 (c 0.5, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (1R,7aS)

(S)-1-(2-(3-(Benzyloxy)prop-1-en-2-yl)pyrrolidin-1-yl)but-3-en-1-oneC18H23NO2[α]D25=-18.2 (c 1.5, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (S)

(S)-8-(Benzyloxymethyl)-1,2,3,8a-tetrahydroindolizin-5(6H)-oneC16H19NO2[α]D25=-4.4 (c 1.8, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (S)

((8S,8aS)-5-Oxo-octahydroindolizin-8-yl)methyl benzoateC16H19NO3[α]D25=-7.4 (c 1.0, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (8S,8aS)

((8R,8aS)-5-Oxo-octahydroindolizin-8-yl)methyl benzoateC16H19NO3[α]D25=-20.1 (c 1.6, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (8R,8aS)

(8S,8aS)-8-(Hydroxymethyl)-hexahydroindolizin-5(1H)-oneC9H15NO2[α]D25=-32.9 (c 1.0, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (8S,8aS)

(8R,8aS)-8-(Hydroxymethyl)-hexahydroindolizin-5(1H)-oneC9H15NO2[α]D25=-15.0 (c 0.5, CHCl3)Source of chirality: l-(−)-prolineAbsolute configuration: (8R,8aS)