Fidel J. López-Herrera

Reaction of aldehydes with stabilized sulfur ylides. Highly stereoselective synthesis of 2,3-epoxy-amides

Abstract Reaction of benzaldehyde ( 1a ), 4 -chloro-benzaldehyde ( 1b ), or 3-nitro-benzaldehyde( 1c ), with N,N-dimethyl-2-(dimethylsulfuranylidene)acetamide ( 2 ), gives only the trans -3-phenyl-2,3-glycidamide derivatives 3a-c in good yields. The same reaction with 2-nitro-benzaldehyde ( 1d ), gives a 15:1 mixture ( trans-cis ) of analogous products 3d . Reaction of 2 with 2,3- O -isopropylidene-D-glyceraldehyde ( 4 ) results in a highly stereoselective synthesis of (2S,3R,4R)- and (2R,3S,4R)-N,N-dimethyl-2, 3-epoxy-4,5- o -isopropylidene-4,5-dihydroxypentanoamides ( 5a ) and ( 5b ), (86:14 at r.t., 96:4 at -5 to 0°C, 5a:5b ). Configurational analysis was made by three different methods: 1) 1 H-NMR coupling constants analysis; 2) comparison with the cis-trans analogous 15a,b and 7a,b , prepared by epoxidation of the cis or trans alkenes 13 and 12 ; and 3) the transformation of the 5a, 7a and 15a (or 5b,7b and 15b ) isomers into the known (3S,4R)-3,4,5-trihydroxypentanoic acid 1,4-lactone ( 10a ) (or 3(R)-isomer, 10b respectively).

Reaction of monosaccharaide derivatives with stabilized sulfur ylides. A highly stereoselective synthesis for C-glycofuranosides

Abstract Stereoselectivity in the formation of glycidic amides by reaction of various aldehydro- and ketosugars [ (1) , (4) , (6) , (8) , (10) and (12) ] with N,N-dimethyl-2-(dimethylsulfuranylidene)acetamide (2) was studied. The reaction with derivatives of reducing cyclohemiacetalic monosaccharides (14) and (21) , gives to α-C-glycofuranosyl-2(S)-hydroxyacetamides with a higher yield and stereoselectivity.

Asymmetric synthesis of 2,3-epoxyamides by reacting monosaccharide derivatives with stabilised sulphur ylides generated in-situ: two-phase method and configurational assignations

Abstract The reaction of 2,3- O -isopropylidene-D-glyceraldehyde 1 ,2,4-ethylidene-D-threose 7 , or 2,3:4,5-di- O -isopropylidene-D-arabinose 9 with N,N-dimethyl-carbamoylmethyldimethylsulphonium chloride and a 10–50% solution of sodium hydroxyde gave the corresponding 2,3-epoxyamides 5, 8 and 10 , and the reaction of 1 , or 5- O -trityl-2,3- O -isopropylidene-D-ribofuranose 13 with N,N-diethylcarbamoylmethyl dimethyl sulphonium chloride and a 10–50% solution of sodium hydroxyde gave the corresponding 2,3-epoxyamides 4 and 14 , respectively, with high yields and variable stereoselectivity.

Completely regioselective oxirane opening of (2S, 3R, 4R)-N,N-dimethyl-2,3-epoxy-4,5-O-osopropyliene-4,5-dihydroxypentanoamide by nitrogen nucleophiles

Abstract The trans -2,3-epoxyamide 3 reacts regioselectively and stereospecifically with nitrogen nucleophiles to give anti α-Nitrogen-β-hydroxyamide derivatives 4–8 . Its highly stereoselective preparation and these opening reactions constitute a useful method for the preparation of many functionalized chiral templates.

Reaction of methyl diazoacetate with 23 0-isopropylidene-D-glyceraldehyde. Stereoselectivity in the synthesis of 2-deoxy-D-aldonates and 2-deoxy-γD-aldonolactones.

Abstract The reaction of 23-O-isopropylidene-D-glyceraldehyde with diazoacetates are revised. In the absence of catalyst the methyl (3S 4R) and (3R 4R)-45-O-isopropylidene- 2-diazo-345-trihydroxypentanoate (4a and 4b) were the new and main products in a high stereoselective reaction (84:16). These products were easily converted into the corresponding 2-deoxy-3-ulosonates (3) 2-deoxyγ-aldonates (6 7 and 8) and 2-deoxy-yD-aldonolactones (9 and 10).

β-Oxy-α-diazo-carbonyl compounds. Part 5: An improved synthesis of β-hydroxy-α-diazo esters derived from monosaccharides and synthetic applications in the chemistry of 3-deoxy-2-ulosonic acids

Abstract Reactions of ethyl 2-diazoacetate with aldehydo sugars and monosaccharide derivatives in their hemiacetal form are reported. The use of diethyl zinc led to an improvement of yields and shorter reaction times compared with neutral conditions as previously described. The resulting products represent potentially useful substrates for the synthesis of 3-deoxy-2-keto-ulosonic acid derivatives. Thus, diazo derivatives from d -mannose were transformed into Ko and 3-epimer Ko derivatives in a straightforward process by reaction with mCPBA.

A New Synthesis of 2-C-Methyl-d-Ribono-1,4-Lactone and the C-9/C-13 Fragment of Methynolide

Abstract The synthesis of the glucosaccharino lactone, 2-C-methyl-D-ribono-1,4-lactone 7 from 2,3-O-isopropylidene-D-glyceraldehyde 1 is reported. Lactone 7 was transformed into (2R,3R)-2,3-dihydroxy-2-methylpentanoic acid 18 (the C-9/C-13 fragment of Methynolid) by two new procedures which improve on existing alternatives: conversion of the epoxide derivative 9 to the episulfide 14 and subsequent reduction; and reductive opening of the 5-bromo derivative of 2,3-O-isopropylidene-2-C-methyl-D-ribono-1,4-lactone and subsequent hydrogenation.

Stereoselective synthesis of 2,3-epoxy-amides by aldol-like condensation of 2,3-O-isopropylidene-D-glyceraldehyde with N,N-diethyl diazoacetamide

Abstract The 1:1 mixture of cis:trans epoxy-amides 5c was obtained quantitatively by condensation of 2,3-O-isopropylidene-D-glyceraldehyde 1 with N,N-diethyl diazoacetamide. Similarly, the reaction of 1 with methyl diazopropionate was studied and gave as the main product the β-ketoester 4b (product of a 1,2-hydrogen shift) and, in a low yield, the glycidic ester 5b (intramolecular nitrogen displacement). The configuration at C-3 of the resultant epoxides of both reactions revealed that the addition step was completely stereoselective. Under similar conditions, compound 6 , methyl 3-hydroxy-2-diazopropionate was unreactive, but with heating gave 7 .

β-Oxy-α-diazo carbonyl compounds. II: Conversion to chiral α-oxy-α'-diazo ketones and photochemical reaction

Abstract Chiral β-oxy-α-diazo methyl ketone was successfully converted to α-oxy-α′-diazo ketone in three steps. The photochemical reaction of this new diazo compound provides an improved synthesis of the 3-hydroxy-2-methyl carboxylate derivative 2 in threo relative configurations via a Wolff rearrangement. The influence of the protective group on the stereochemical result of the photochemical reaction is discussed.

β-Oxy-α-diazo-carbonyl compounds. Part 6: Synthesis and reactivity of 3-deoxy-2-diazo-esters derived from monosaccharides. Applications in the synthesis of 2-C-alkyl-KDO analogues and related compounds

Abstract Reactions of 6- O -protected diazo derivatives 8 , 9 and 10 with transition metals Rh(II) and Cu(II) under a variety of different conditions of solvents and temperatures, were studied in order to obtain 2- C -alkyl analogues of KDO. In fact, these types of products ( 11 , 12 ) were obtained in good yields when Rh(II) was used as a catalyst in benzene. The interesting seven-membered ring products ( 13 ) were obtained only for 8 and 9 , as single diastereoisomers and their formations were favored when Cu(II) catalysts were used.