Improved preparation of β-hydroxy-α-amino acids: direct formation of sulfates by sulfuryl chloride

Two β-(alkyl)-β-hydroxy-α-amino acids [alkyl = But, BnO–(CH2)3–] have been synthesized by a sequence based on Sharpless asymmetric dihydroxylation. The key sulfate intermediates were prepared from enantiomerically enriched diols by direct treatment with sulfuryl chloride. The scope and the appropriate conditions for sulfate formation have also been studied.

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(4S,5R)-4-Ethoxycarbonyl-5-tert-butyl-1,2,3-dioxathiolane-2,2-dioxideC9H16SO6[α]D = +65.2 (c 0.885, CHCl3).Source of chirality: Sharpless asymmetric dihydroxylation (DHQD)2PHALAbsolute configuration: (4S,5R)

Ethyl (2R,3R)-2-azido-3-hydroxy-4,4-dimethyl-pentanoateC9H17N3O3[α]D = −52 (c 0.88, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylation (DHQD)2PHALAbsolute configuration: (2R,3R)

Ethyl (2R,3R)-2-(tert-butoxycarbonyl)amino-3-hydroxy-4,4-dimethyl-pentanoateC14H27NO3[α]D = −7.5 (c 0.90, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylation (DHQD)2PHALAbsolute configuration: (2R,3R)

Ethyl (2S,3R)-6-benzyloxy-2-3-dihydroxy-hexanoateC15H22O5Ee = 96.8% (HPLC)[α]D = +8.5 (c 1.00, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylation (DHQD)2PHALAbsolute configuration: (2S,3R)

(4S,5R)-4-Ethoxycarbonyl-5-(3-benzyloxy)propyl-1,2,3-dioxathiolane-2,2-dioxideC15H20O7S[α]D = +17.2 (c 1.35, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylation (DHQD)2PHALAbsolute configuration: (4S,5R)

Ethyl (2R,3R)-2-azido-3-hydroxy-6-benzyloxy-hexanoateC15H21N3O4[α]D = +33.5 (c 0.830, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylation (DHQD)2PHALAbsolute configuration: (2R,3R)

Ethyl (2R,3R)-2-{[(tert-butoxy)carbonyl]amino}-3-hydroxy-6-benzyloxy-hexanoateC20H31NO6[α]D = −14.2 (c 0.720, CHCl3)Source of chirality: Sharpless asymmetric dihydroxylation (DHQD)2PHALAbsolute configuration: (2R,3R)