Doubly diastereoselective conjugate additions of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)amide to enantiopure ε-O-protected α,β-unsaturated esters derived from d-ribose

Enantiopure ε-O-silyloxy- and ε-O-benzyloxy-α,β-unsaturated esters derived from d-ribose, each containing a cis-dioxolane unit, display excellent (⩾95:5 dr) levels of diastereofacial directing ability upon conjugate addition of achiral lithium N-benzyl-N-isopropylamide. In contrast to the corresponding enantiopure ε-O-silyloxy-α,β-unsaturated ester derived from l-tartaric acid, which contains a trans-dioxolane unit, the conjugate additions of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)amide to its cis-configured counterpart result in doubly diastereoselective ‘matched’ and ‘mismatched’ reaction pairings in which the inherent reagent control serves to augment or oppose, respectively, the established substrate diastereocontrol.

Conjugate addition of the antipodes of lithium N-benzyl-N-(α-methylbenzyl)amide to cis-dioxolane containing ε-O-protected α,β-unsaturated esters results in doubly diastereoselective ‘matched’ and ‘mismatched’ reaction pairings.Figure optionsDownload as PowerPoint slide

(R,R)-3,4-Dihydroxy-3,4-O-isopropylidenedihydrofuran-2(3H)-oneC7H10O4[α]D25=-113 (c 1.0 in H2O)Source of chirality: d-isoascorbic acidAbsolute configuration: (R,R)

tert-Butyl (4S,5R,E)-4,5,6-trihydroxy-4,5-O-isopropylidenehex-2-enoateC13H22O5[α]D25=+30.6 (c 1.0 in CHCl3)Source of chirality: d-isoascorbic acidAbsolute configuration: (4S,5R,E)

tert-Butyl (4S,5R,Z)-4,5,6-trihydroxy-4,5-O-isopropylidenehex-2-enoateC13H22O5[α]D25=+127.6 (c 1.0 in CHCl3)Source of chirality: d-isoascorbic acidAbsolute configuration: (4S,5R,Z)

Methyl (4S,5R,E)-4,5,6-trihydroxy-4,5-O-isopropylidenehex-2-enoateC10H16O5[α]D21=+17.1 (c 1.0 in CHCl3)Source of chirality: d-isoascorbic acidAbsolute configuration: (4S,5R,E)

Methyl (4S,5R,Z)-4,5,6-trihydroxy-4,5-O-isopropylidenehex-2-enoateC10H16O5[α]D25=+144.6 (c 1.0 in CHCl3)Source of chirality: d-isoascorbic acidAbsolute configuration: (4S,5R,Z)

Methyl (4S,5R,E)-4,5-dihydroxy-4,5-O-isopropylidene-6-(p-nitrobenzoyloxy)hex-2-enoateC17H19NO8[α]D25=+3.6 (c 1.0 in CHCl3)Source of chirality: d-isoascorbic acidAbsolute configuration: (4S,5R,E)

Methyl (4S,5R,Z)-4,5-dihydroxy-4,5-O-isopropylidene-6-(p-nitrobenzoyloxy)hex-2-enoateC17H19NO8[α]D25=+176.5 (c 1.0 in CHCl3)Source of chirality: d-isoascorbic acidAbsolute configuration: (4S,5R,Z)

(2R,3R,4S,5S)-2-Methoxy-3,4-dihydroxy-3,4-O-isopropylidene-5-iodomethyltetrahydrofuranC9H15IO4[α]D25=-65.3 (c 1.0 in CHCl3)Source of chirality: d-riboseAbsolute configuration: (2R,3R,4S,5S)

(4S,5R)-2,2-Dimethyl-4-hydroxymethyl-5-vinyl-1,3-dioxolaneC8H14O3[α]D25=-40.0 (c 1.0 in CHCl3)Source of chirality: d-riboseAbsolute configuration: (4S,5R)

(4S,5R)-2,2-Dimethyl-4-(tert-butyldimethylsilyloxymethyl)-5-vinyl-1,3-dioxolaneC14H28O3Si[α]D25=+1.6 (c 1.0 in CHCl3)Source of chirality: d-riboseAbsolute configuration: (4S,5R)

(4S,5R)-2,2-Dimethyl-4-(benzyloxymethyl)-5-vinyl-1,3-dioxolaneC15H20O3[α]D25=+1.7 (c 1.0 in CHCl3)Source of chirality: d-riboseAbsolute configuration: (4S,5R)

tert-Butyl (4R,5S,E)-4,5-dihydroxy-4,5-O-isopropylidene-6-(tert-butyldimethylsilyloxy)hex-2-enoateC19H36O5Si[α]D25=+9.4 (c 1.0 in CHCl3)Source of chirality: d-riboseAbsolute configuration: (4R,5S,E)

tert-Butyl (4R,5S,E)-4,5-dihydroxy-4,5-O-isopropylidene-6-benzyloxyhex-2-enoateC20H28O5[α]D25=+19.7 (c 1.0 in CHCl3)Source of chirality: d-riboseAbsolute configuration: (4R,5S,E)

tert-Butyl (S,Z)-4,5-dihydroxy-4,5-O-isopropylidene-6-(tert-butyldimethylsilyloxy)hex-3-enoateC19H36O5Si[α]D25=-24.4 (c 1.0 in CHCl3)Source of chirality: d-riboseAbsolute configuration: (S,Z)

tert-Butyl (3R,4R,5S)-3-(N-benzyl-N-isopropylamino)-4,5-dihydroxy-4,5-O-isopropylidene-6-(tert-butyldimethylsilyloxy)hexanoateC29H52NO5Si[α]D25=+36.0 (c 1.0 in CHCl3)Source of chirality: d-riboseAbsolute configuration: (3R,4R,5S)

tert-Butyl (3R,4R,5S)-3-(N-benzyl-N-isopropylamino)-4,5-dihydroxy-4,5-O-isopropylidene-6-benzyloxyhexanoateC30H43NO5[α]D25=+10.6 (c 1.0 in CHCl3)Source of chirality: d-riboseAbsolute configuration: (3R,4R,5S)

tert-Butyl (3R,4R,5S,αS)-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5-dihydroxy-4,5-O-isopropylidene-6-(tert-butyldimethylsilyloxy)hexanoateC34H53NO5Si[α]D25=+13.8 (c 1.0 in CHCl3)Source of chirality: d-ribose/asymmetric synthesisAbsolute configuration: (3R,4R,5S,αS)

tert-Butyl (3R,4R,5S,αS)-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5-dihydroxy-4,5-O-isopropylidene-6-benzyloxyhexanoateC35H45NO5[α]D25=+3.3 (c 1.0 in CHCl3)Source of chirality: d-ribose/asymmetric synthesisAbsolute configuration: (3R,4R,5S,αS)

tert-Butyl (3R,4R,5S,αR)-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5-dihydroxy-4,5-O-isopropylidene-6-(tert-butyldimethylsilyloxy)hexanoateC34H53NO5Si[α]D25=+34.7 (c 1.0 in CHCl3)Source of chirality: d-riboseAbsolute configuration: (3R,4R,5S,αR)

tert-Butyl (3S,4R,5S,αR)-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5-dihydroxy-4,5-O-isopropylidene-6-(tert-butyldimethylsilyloxy)hexanoateC34H53NO5Si[α]D25=-10.0 (c 1.0 in CHCl3)Source of chirality: d-ribose/asymmetric synthesisAbsolute configuration: (3S,4R,5S,αR)

tert-Butyl (3R,4R,5S,αR)-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5-dihydroxy-4,5-O-isopropylidene-6-benzyloxyhexanoateC35H45NO5[α]D25=+25.8 (c 1.0 in CHCl3)Source of chirality: d-riboseAbsolute configuration: (3R,4R,5S,αR)

tert-Butyl (3S,4R,5S,αR)-3-[N-benzyl-N-(α-methylbenzyl)amino]-4,5-dihydroxy-4,5-O-isopropylidene-6-benzyloxyhexanoateC35H45NO5[α]D25=-26.5 (c 1.0 in CHCl3)Source of chirality: d-ribose/asymmetric synthesisAbsolute configuration: (3S,4R,5S,αR)

tert-Butyl (3R,4R,5S)-3-amino-4,5,6-trihydroxy-4,5-O-isopropylidenehexanoateC13H25NO5[α]D25=+20.7 (c 1.0 in CHCl3)Source of chirality: d-ribose/asymmetric synthesisAbsolute configuration: (3R,4R,5S)

tert-Butyl (3R,4R,5S)-3-N-isopropylamino-4,5,6-trihydroxy-4,5-O-isopropylidenehexanoateC16H31NO5[α]D25=-4.5 (c 1.0 in CHCl3)Source of chirality: d-ribose/asymmetric synthesisAbsolute configuration: (3R,4R,5S)

tert-Butyl (3R,4R,5S)-3-amino-4,5-dihydroxy-4,5-O-isopropylidene-6-(tert-butyldimethylsilyloxy)hexanoateC19H39NO5Si[α]D25=-6.7 (c 1.0 in CHCl3)Source of chirality: d-ribose/asymmetric synthesisAbsolute configuration: (3R,4R,5S)

tert-Butyl (3R,4R,5S)-3-N-isopropylamino-4,5-dihydroxy-4,5-O-isopropylidene-6-(tert-butyldimethylsilyloxy)hexanoateC22H45NO5Si[α]D25=-8.1 (c 1.0 in CHCl3)Source of chirality: d-ribose/asymmetric synthesisAbsolute configuration: (3R,4R,5S)