Glycosyl imines

Keywords aza-Diels-Alder reactions, N-glycosyl imines as dienophiles, piperidine... 

Coordination of the Lewis acid zinc(II) chloride to glycosyl imines has strong influence on the stereodifferentiation in nucleophilic addition reactions to these imines (see Scheme 3). 

The conformation is proved by a significant NOE between the aldimine proton and the anomeric proton [17,24]. In polar solvents, free cyanide attacks the complex A, preferably from the unshielded Si-side. In unpolar solvents like chloroform, cyanide is not set free from the silyl derivative. The activation of the cyanide proceeds by an interaction between the exo chloride of the zinc complex and the silyl group. Thus, the cyanide is directed to the Re-side of the glycosyl imine (see Scheme 8). This nucleophilic attack produces L-aminonitriles with moderate or good stereoselectivity (S R 3-9 1) and high yields. 

Carbohydrate-derived homoallylamines have been demonstrated as being useful chiral synthons for the stereoselective synthesis of P-amino acids. With allyltribu-tylstannane or allyltrimethylsilane as the nucleophiles, glycosyl imines form homoallylamines with high efficiency [29-31]. Promoted by SnCl4, the nucleophile al-lyltributylstannane attacks from the stoically less hindered side. 

The product 14a is obtained in excellent diastereoselectivity (> 25 1) (Scheme 11). Zinc (II) chloride is not able to promote the nucleophilic addition. If the reaction temperature can be held below 10 °C, no anomerization is observed. The Si-side attack is rationalized by a complex B between SnCl4 and the glycosyl imine 7a (Scheme 12). 

Reactions of glycosyl imines derived from aliphatic aldehydes must be carried out at low temperature due to their higher sensibility towards anomerization. Yields and diastereoselectivity rank in the same region as those achieved for galactosyl homo-allylamines. The results of different stereoselective allylations, are summarized in Table 4.1. 

Glycosyl imines from aliphatic aldehydes are sensitive to anomerization. However, the anomerization can be avoided by conducting the reactions at lower temperatures (-78 °C). Recrystallization of the crude products (methanol/water for aliphatic, heptane for aromatic compounds) gave the diastereomerically pure D-amino acid amides (Table 4.3). 

The high stereoselectivity can be explained again by means of the zinc complex A (see Scheme 3). The nucleophilic isonitrile attacks the glycosyl imine from the steri-cally less shielded Re-side. The bulky pivaloyl group at the 2-position and the formed zinc complex block the Si-side efficiently. The exchange of the pivaloyl for the acetyl group decreases the selectivity of the reaction (10 1 instead of 30 1) [13]. 

Glycosyl imines are not very reactive dienophiles in [4 + 2] cycloaddition reactions. However, they can be subjected to cycloaddition reactions after activation with Lewis acids [51]. TV-Galactosyl imines 7 were shown to react with isoprene in the presence of zinc(II) chloride to give the corresponding 4-methyl piperidine derivatives 43 (Scheme 25). 

The reaction can be carried out with glycosyl imines derived from a broad range of aliphatic, aromatic, and heteroaromatic aldehydes. Piperidinones of opposite enantiomeric configuration are available by applying the corresponding D-arabinosyl imines 18 [32]. The major diastereomers are isolated by flash chromatography or recrystallization in high yields. The 2-propyl dehydropiperidine 46a can be readily converted into enantiomerically pure (/ )-coniine hydrochloride 47 (Scheme 28). 

The chiral piperidinones 46 formed by the reaction between Danishefsky s diene and the glycosyl imines are valuable synthons for the synthesis of higher substituted piperidine derivatives. 2,6-Disubstituted piperidinones 49 are obtained by addition of organocuprates complexes with boron trifluoride [53]. The reaction pathway is illustrated in Scheme 30. 

Carbohydrate-derived auxiliaries exhibit an efficient stereoselective potential in a number of nucleophilic addition reactions on prochiral imines. a-Amino acids, P amino acids and their derivatives can be synthesized in few synthetic steps, and with high enantiomeric purity. A variety of chiral heterocycles can readily be obtained from glycosyl imines by stereoselective transformations, providing evidence that carbohydrates have now been established as useful auxiliaries in stereoselective syntheses of various interesting classes of chiral compounds. 

Additions to Glycosyl Imines and Other Nucleophilic Additions... 

STEREOSELECTIVE ADDITION AND SUBSTITUTION REACTIONS 10.3.1 Additions to Glycosyl Imines and Other Nucleophilic Additions... 

J.-P. Praly, D. Senni, R. Faure, and G. Descotes, Synthesis and structure of bromo glycosyl imines readily obtained from protected glycosyl azides. Tetrahedron, 51 (1995) 1697-1708. 

Glycosyl Imines and Amines for the Synthesis of Glycosyl Heterocycles. . 41... 

Carbohydrates are inexpensive and renewable natural products which contain numerous functional groups and chiral centers. Utilizing their pronounced complexing abilities and their content of chiral information, carbohydrates are applied as chiral auxiliaries in Diels-Alder and aza-Diels-Alder reactions. The method involves the use of Lewis acid catalysts with different complexing properties. Thus, dienes of low reactivity can be transformed to their cycloadducts with high asymmetric induction. The use of N-glycosyl imines as the dienophiles offers stereoselective access to enantiomerically pure piperidine derivatives, e.g. the alkaloids coniin and anabasin. 

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