The preparation of amino sugars and branched-chain sugars by palladium-catalyzed, allylic substitution of alkyl hex-2-enopyranosides

Abstract

This paper is dedicated to Prof. Raymond U . Lemieux on the occasion of his 60th birthday HANS H. BAERand ZAHER S. HANNA. Can. J. Chem. 59,889 (1981). Ethyl 4,6-di-0-acetyl-2,3-dideoxy-a-~-erythro-hex-2-enopyranoside (1) in the presence of triphenylphosphine and a catalytic amount of tetrakis(triphenylphosphine)palladium(O) reacted with a variety of amines or with reactive methylene compounds to give high yields of products aminated or C-alkylated, respectively, in an allylic position. Some analogous experiments were performed using the P-D-erythro anomer (2) and the a-D-threo epimer (3) of 1. The constitutions and configurations of the new products were established by means of mass spectra, 13C-and 'H-nmr spectra, and optical rotation data. The reactions of 1 were found to be highly regio-and stereoselective, giving almost exclusively Csubstituted 2-enopyranosides with retention of configuration, except in the case of dibenzylamine which produced a mlxture of the corresponding enoside and its 2-substituted, 3,Cunsaturated isomer having the a-D-threo configuration. The reactions of 2 appeared slightly less selective although they, too, furnished mainly 4-substituted 2-enopyranosldes with retention of configuration. Regioselectivity was low or lacking in two C-alkylations performed with 3, which gave mixtures of Csubstituted 2-enosides and 2-substituted 3-enosides. Some aspects of conformation and optical rotation in enopyranosides are discussed.HANS H. BAER et ZAHER S. HANNA. Can. J. Chem. 59,889 (1981).L e compose C t h y l -4 , 6 -d i -O -a c e t y I -2 , 3 -d i d e s o x y -a -~n o p y r a n o s i d e Introductioncally substituted product. The palladium species Recently we communicated (1) the first results of liberated upon collapse of the intermediary corna study concerning the potential utility of or-plex is reconverted into a catalytically active form ganopalladium reagents for the functionalization of by the action of the excess of triphenylphosphine carbohydrates. The present article reports full de-which is provided. A high degree of regioselectivity tails of the work and includes some additional re-and stereocontrol is normally observed in these sults which have since been elaborated. In connec-substitutions (6), although certain exceptions to tion with our current interest in the development of this welcome trend have been noted and discussed. methods for the synthesis of unusual amino, deoxy, As Our chief substrate for an the unsaturated, and branched-chain sugars (2), we de-utility of the method in the carbohydrate field,[ we cided to examine whether the palladium-catalyzed chose the crystalline ethyl 4,6-di-0-acetyl-2,3-disubstitution of allylic acetates by amines or reac-de0xy-cr-~-er~thro-hex-2-eno~~ranoside (I). his tive methylene compounds (3-6) might be em-compound is readily prepared (9) from commerplayed to advantage in carbohydrate chemistry. In c i a l l~ available D-glucal tfiacetate-For some anthis reaction, which represents one of the numer-cillary experiments, to be performed in the ...

Amine-linked diglycosides: Synthesis facilitated by the enhanced reactivity of allylic electrophiles, and glycosidase inhibition assays

“…Hanna and Baer observed [ 20 ] that 2,3-unsaturated-4-amino-α-glycopyranosides have 13 C chemical shifts for C-1 in the range 93.8–94.1 ppm, irrespective of the C-4 configuration. In our assessment the C-1 chemical shifts for 25 (94.3) and 26 (94.1) are in broad agreement with these values, whereas 24 (98.9) has a significantly higher shift.…”

“…Unsaturated carbohydrates, similar to those described here, have also been reported to undergo Mitsunobu reaction with simple, non-carbohydrate nucleophiles [ 29 – 30 ]. The palladium-catalysed allylic amination reaction on unsaturated pyranose rings was pioneered thirty years ago by Hanna and Baer [ 19 – 20 ], and has more recently been reinvestigated with rather simple nitrogen nucleophiles [ 30 – 31 ]. Carbohydrate amines have been used as nucleophiles in allylic amination by Shing to form valienamine pseudodisaccharides [ 21 ].…”

Arylation de glycals catalysée par les sels de palladium: nouvelle synthèse de C-glycosides

“…Un tel type de fragmentation a t t t Cgalement observt pour des derivts du dihydropyranne possedant une ramification en position 2 (6c). 11 est j. noter que la fragmentation rktrodienique, caractkristique (9,16,17) Les donnees de rmn 'H concernant les composes rCsultant de l'arylation de ces glycals sont rCunies dans le tableau 2. ides signaux correspondants aux protons arornatiques perrnettent de fixer sans arnbiguitC la position de la partie glycosidique sur I'arornatique sauf dans le cas du p-fluoroanisole pour lequel nous avons eu recours h la rmn ''C. C'est la valeur de la constante de couplage entre le carbone arornatique liC h la partie glucidique et le fluor qui permet de trancher.…”

Palladium(0)-Catalyzed Allylation of Heterocyclic Nucleophiles with Unsaturated Carbohydrates

“…This methodology has been applied in carbohydrate chemistry with more or less success using carbon, 2 oxygen, 3 and nitrogen 4 nucleophiles. If the direct palladium(0)-catalyzed substitution of allylic acetates or carbonates with a heterocyclic base that could react as an ambident nucleophile is well documented, 1b,5 the application of this methodology in carbohydrate chemistry is less common, although it could be useful for the direct introduction of nucleobases onto a sugar framework.…”

“…This methodology can be used to prepare numerous analogues of nucleosides containing a pyranose sugar moiety. 4 (16 mg, 14 mmol), dppb (12 mg, 28 mmol), and the unsaturated carbohydrate 2 (100 mg, 0.28 mmol) in THF (5 mL) was added the corresponding heterocyclic nucleophile (0.42 mmol, 1.5 equiv). The solution was stirred at 50°C for 2 h. Evaporation of the solvent under reduced pressure gave a residue that was purified by column chromatography on silica gel to give the corresponding compound 3.…”