Enantioselective Diels-Alder Reaction with an α-Chloronitrose Dienophile Derived from 5-O-Acetyl-2,3-isopropylidenedioxy-d-ribose

Abstract

Crystalline 5-O-acetyl-2,3-isopropylidenedioxy-D-ribonolactone oxime (8) was synthesised from D-ribose in 40% overall yield. The chloronitroso dienophile 3b was obtained from 8 by oxidation with t-BuOCl and underwent asymmetric Diels-Alder reaction with cyclic and acyclic dienes 10-13 to give crystalline adducts 14a-17a in good yield and excellent enantiomeric excess (93-99%).A. Defoin et al. PAPER Synthesis 2000, No. 12, 1719-1726 ISSN 0039-7881 © Thieme Stuttgart · New York rate was fast with cyclohexadiene (10) and slow (ca 1-2 d) with pentadienoic acid (11) and sorbic acid (12), leading to the corresponding chiral adducts 14a-16a as crystalline hydrochlorides in 75-86% yield (by direct precipitation with anhydrous diethyl ether). Hexa-2,4-diene (13) [ca 50:50 mixture of (E,E)-and (E,Z)-isomers 30 ] reacted rapidly with 3b and gave a mixture of the cis-adduct 17a and its trans-isomer (20%). The cis adduct 17a was isolated in 60% yield as a crystalline hydrochloride after aqueous extraction, as described by Kresze and Vasella. 20 Ribonolactone (9), which resulted from 3b, could be isolated from the organic phase. Scheme 2Benzyl (3S,6R)-3,6-Dimethyl-3,6-dihydro-2H-1,2-oxazine-2carboxylate (17b)To an aqueous solution of 17a (8 mL) [from aqueous extraction of the reaction mixture of 3b (0.82 mmol) and 13 (0.4 mL, 3.5 mmol, 2 equiv of (E,E)-diene)] was added dioxane (1 mL), NaHCO 3 (0.28 g, 3.4 mmol, 4 equiv) and ClCO 2 Bn (0.132 mL, 0.94 mmol, 1.2 equiv). The reaction mixture was stirred for 2 h at r.t., then extracted with Et 2 O (2 × 10 mL), the organic phase dried (MgSO 4 ) and evaporated. Purification by FC (CH 2 Cl 2 ) gave 17b (0.13 g, 63%) (as a mixture with 20% of trans-isomer); colorless resin.

Asymmetric synthesis of the l-fuco-nojirimycin, a nanomolar α-l-fucosidase inhibitor

“…This ee was similar to the one observed when hexadienoic acid was reacted with the dienophile 6b. 17 Regarding the overall yields and the ee values which are given in Table 1, the mannose derivative 4 gave the best results among these dienophiles.…”

“…This chiral dienophile had been developed by Kresze and Vasella. 15 Using the same methodology and the previously reported concurrent chloro-nitroso dienophiles 6a,b in the 5-O-trityl- 16 and the 5-O-acetyl-D D-ribose 17 series, respectively, the enantiomeric adduct has been prepared. An interesting comparison of these parent dienophiles is now possible.…”

“…This is probably due to the difficulty in purifying the amorphous initial oxime 5a, compared to the nicely crystallised acetylated one 5b. 17 Determined enantiomeric excess (ee) 19 of L L-8a was good (ca. 95%) and independent of the 5-substitution of the dienophile.…”

Chlorination of Oximes with Aqueous H2O2/HCl System: Facile Synthesis of gem-Chloronitroso- and gem-Chloronitroalkanes, gem-Chloronitroso- and gem-Chloronitrocycloalkanes

“…gem-Chloronitrosoalkanes and cycloalkanes have found use in the synthesis of gemchloronitro compounds, 20,21 dihalides, 22,23 oxazines, [24][25][26][27][28][29][30][31][32][33][34][35][36] and O-allylated oximes. 37 gem-Chloronitroalkanes and cycloalkanes are used in the synthesis of nitro compounds, 20,38,39 esters of a,b-unsaturated acids, [40][41][42] and anitroalkylphosphonates.…”

“…37 gem-Chloronitroalkanes and cycloalkanes are used in the synthesis of nitro compounds, 20,38,39 esters of a,b-unsaturated acids, [40][41][42] and anitroalkylphosphonates. 43 Procedures for the synthesis of gem-chloronitroso compounds are based on chlorination of oximes with chlorine, 21,22,[44][45][46][47] tert-butyl hypochlorite, 36 and N-tert-butyl Nchlorocyanamide. 48 Since low-molecular-weight gemchloronitroso compounds are unstable, syntheses with the use of these compounds are generally performed without their isolation.…”