Diastereoselective synthesis of 3,4-disubstituted 5-(p-tolylsulfinyl)-5,6-dehydropiperidin-2-ones: chirality transfer in the enantioselective synthesis of ethyl (+)-(3S,4aS,7aS)-1-oxo-octahydro-1H-cyclopenta[c]pyridine-3-carboxylate

The base-mediated reaction of enantiomerically pure α-sulfinylketimine (+)-1 with (E)-α,β-disubstituted propenoate esters afforded 3,4-disubstituted-5-(p-tolylsulfinyl)-5,6-dehydropiperidin-2-ones 9α-13α and 14 with high or complete diastereoselectivity. A sole diastereomer of the four possible ones, with regard to the nature of ester, was isolated, which revealed the stereocontrol of the chiral sulfinyl group in the Michael reaction and transenolization steps. In addition, the enantioselective synthesis of ethyl (+)-(3S,4aS,7aS)-1-oxo-octahydro-1H-cyclopenta[c]pyridine-3-carboxylates (+)-17α is described (five steps; 47% yield; ee ⩾97%). The absolute configuration of stereocentres introduced in (+)-17α was assigned on the basis of 1H NMR data.

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(−)-(SS,5a′S,8a′R)-9′-[(4-Methylphenyl)sulfinyl]-1′,5a′,6′,7′,8′,8a′-hexahydro-5′H-spiro[cyclohexane-1,3′-cyclopenta[d][1,3]oxazolo[3,4-a]pyridin]-5′-oneC22H27NO3See ⩾97%[α]D25=-45.7(c1.7,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: SS,5a′S,8a′R

(−)-(SS,5a′S,9a′R)-10′-[(4-Methylphenyl)sulfinyl]-5a′,6′,7′,8′,9′-9a′-hexahydrospiro[cyclohexane-1,3′[1,3]oxazolo[3,4-b]isoquinolin-5′(1′H)-oneC23H29NO3See ⩾97%[α]D25=-70.3(c0.7,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: SS,5a′S,9a′R

(+)-(SS,6′R,7′S)-8′-[(4-Methylphenyl)sulfinyl]-6′,7′-diphenyl-6′,7′-dihydrospiro[cyclohexane-1,3′-[1,3]oxazolo[3,4-a]pyridin]-5′(1′H)-oneC31H31NO3See ⩾97%[α]D25=+314.05(c0.42,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: SS,6′R,7′S

(+)-(SS,6′S,7′S)-6′,7′-8′-[(4-Methylphenyl)sulfinyl]-6′,7′-diphenyl-6′,7′-dihydrospiro[cyclohexane-1,3′-[1,3]oxazolo[3,4-a]pyridin]-5′(1′H)-oneC31H31NO3See ⩾97%[α]D25=+154.05(c0.6,CHCl3)Source of chirality:asymmetric synthesisAbsolute configuration: SS,6′S,7′S

(+)-(SS,6′S,7′S)-6′-Methyl-7′-8′-[(4-methylphenyl)sulfinyl]-7′-phenyl-6′,7′-dihydrospiro[cyclohexane-1,3′-[1,3]oxazolo[3,4-a]pyridin]-5′(1′H)-oneC26H29NO3See ⩾97%[α]D25=+90.1(c0.74,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: SS,6′S,7′S

(+)-(SS,7′R)-8′-[(4-Methylphenyl)sulfinyl]-7′-(trifluoromethyl)-6′,7′-dihydrospiro[cyclohexane-1,3′-[1,3]oxazolo[3,4-a]pyridin]5′(1′H)-oneC20H22F3NO3See ⩾97%[α]D25=+50.4(c0.4,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: SS,7′R

(+)-(5a′S,8a′S,9a′S)-Octahydro-5′H-spiro[cyclohexane-1,3′-cyclopenta[d][1,3]oxazolo[3,4-a]pyridin-5′-oneC15H23NO2ee ⩾97%[α]D25=+42.0(c0.7,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: 5a′S,8a′S,9a′S

(+)-(3S,4aS,7aS)-3-(Hydroxymethyl)octahydro-1H-cyclopenta[c]pyridin-1-oneC9H15NO2ee ⩾97%[α]D25=+16.8(c0.1,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: 3S,4aS,7aS

Ethyl(+)-(3S,4aS,7aS)-1-oxooctahydro-1H-cyclopenta[c]pyridine-3-carboxylateC11H17NOee ⩾97%[α]D25=+2.1(c2.1,CHCl3)Source of chirality: asymmetric synthesisAbsolute configuration: 3S,4aS,7aS