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Carbocyclen aus Monosacchariden. III. Zur Diastereoselektivität der Bildung von Cyclopentanderivaten. Umsetzungen in der Galactosereihe
Author(s) -
Bernet Bruno,
Vasella Andrea
Publication year - 1979
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19790620737
Subject(s) - chemistry , nitrone , anomer , intramolecular force , stereochemistry , cycloaddition , conformational isomerism , medicinal chemistry , organic chemistry , molecule , catalysis
Carbocycles from monosaccharides. III. Concerning the diastereoselective formation of cyclopentane derivatives. Transformations in the galactose series. The diastereoselectivity of the intramolecular nitrone‐olefine cycloaddition of 1 , 3 and 4 (Scheme 1) , yielding only 2 , 5 and 6 but none of the isomers 8 , 9 and 10 is explained by assuming a kinetic control and postulating that the relative activation energies of the two relevant transition states in the cyclization of e.g. 1 can be estimated from the conformers A and B , the latter being destabilized by a synperiplanar arrangement of the nitrone function and the 2‐alkoxy‐group (Scheme 2) . It is further postulated, that this destabilization is responsible for the formation of (2,3)‐ trans configurated products. Since 2 , 5 and 6 are presumably thermodynamically more stable than 8 , 9 and 10 , a case was investigated, where the cycloaddition can either give thermodynamically less stable (2,3)‐ trans ‐product such as 12 or a thermodynamically more stable (2,3)‐ cis ‐product such as 13. 12 and 13 could both be formed from the aldehyde 25 via the nitrone 11 ( Schemes 3 and 5 ). Treatment of the galactoside 16 first with Zn in aqueous butanol (forming among other products 25 and its 2‐debenzyl‐oxy‐derivative) and then with N ‐Methyldroxylamine yielded the isoxazolidines 12 (72%), 13 (2%) and 27 (7%) ( Schemes 4 and 6 ). Similarily, the anomeric silylated galactosides 17 and 23 gave 29 (78% from 17 , 77% from 23 ) and 27 (5% and 3%). Upon desilylation, 29 gave 32 , which was converted into 12 . The structure of the isoxazolidines was unambiguously deduced from their NMR. spectra and those of their derivatives 33 and 34 . Compound 32 was further transformed into its deoxyderivative 36 . The high diastereoselectivity of the cycloaddition restricts the number of diastereomeric, pentasubstituted cyclopentanes available by this method. However, cyclization of the 2‐Hydroxy‐aldehyde 37 ( Scheme 8 ) gave the kinetically less favoured isomer 40 in a higher proportion, showing the differential influence of hydrogen‐bonds on the relevant activation energies. Thermolysis of 32 gave 40 (79%) and 41 (11%). The structure of 41 was deduced from its NMR. spectra and those of its derivatives 42 and 43 . Thermolysis of 29 gave, after desilylation, 41 (42%), 40 (22%) and 32 (13%) and thermolysis of 6 lead to a 25 : 75 equilibrium with 44 (combined yield 90%). These transformations illustrate means leading to additional isomers and are in agreement with the proposed explanation of the diastereoselectivity in question.