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Lewis acid promoted endocyclic cleavage of glycosides and related acetals

Olsson, Roger LU (1997)
Abstract
This thesis is a summary of five papers concerning endocyclic cleavage of glycosides and related acetals. Simple lactol ethers undergo endocyclic cleavage to give acyclic chain extended products on treatment with organoaluminium and organotitanium reagents. The first examples where organotitanium reagents induced alkylative endocyclic cleavage of carbohydrates is presented. The best conditions for the alkylative transfer of a methyl group to benzyl 2-deoxy-2-C-methyl-4-O-(tert-butyldimethylsilyl)-a-D-arabinopyranoside were the application of one equivalent of AlMe3 followed by four equivalents of MeTiCl3 generated by mixing TiCl4 and ZnMe2 2:1, or alternatively, treatment with two equivalents of a mixture of Me2TiCl2 and ZnMe2 1:1. Both... (More)
This thesis is a summary of five papers concerning endocyclic cleavage of glycosides and related acetals. Simple lactol ethers undergo endocyclic cleavage to give acyclic chain extended products on treatment with organoaluminium and organotitanium reagents. The first examples where organotitanium reagents induced alkylative endocyclic cleavage of carbohydrates is presented. The best conditions for the alkylative transfer of a methyl group to benzyl 2-deoxy-2-C-methyl-4-O-(tert-butyldimethylsilyl)-a-D-arabinopyranoside were the application of one equivalent of AlMe3 followed by four equivalents of MeTiCl3 generated by mixing TiCl4 and ZnMe2 2:1, or alternatively, treatment with two equivalents of a mixture of Me2TiCl2 and ZnMe2 1:1. Both yield and diastereoselectivities were comparable with those of the reaction with AlMe3 but titanium reagents were more reactive and could be applied at much lower temperatures than aluminium. A number of pentopyranosides were treated with Me3Al in order to investigate the influence of structural parameters on the methyl group transfer in the endocyclic cleavage reaction of these substrates. Semiempirical and quantum chemical computations indicate that the intermediate formed prior to the selectivity-determing methyl transfer step in the reaction between glycosides and trimethyl aluminium is a strongly hydrogen bonded intermediate wich is proposed to be an important selectivity promoting factor in the alkyl transfer. Combination of Lewis acids and nucleophilic reagents triggered endocyclic cleavage of the furanosidic ring of methyl furanosides resulting in the attachment of the nucleophilic group at C-1 of the carbohydrate. The stereoselectivity in the C-C bond forming step was low for the 2-deoxy furanosides but very high (dr 1:99) for the furanosides carrying a methoxy group in the 2-position when a combination of TiCl4 and ZnMe2 was used. Different selectivities were obtained with ZnMe2 as compared to Me3Al. Reagents based on several organometallic reagents Al, Si, Ti, and Zn in combination with TiCl4. Stereoselective allylation of benzyl pentopyranosides, employing a combination of AlEt2Cl and allyl or crotyl stannane giving a C-7 segment of halichomycin, were investigated. (Less)
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author
opponent
  • Oscarson, Stefan
organization
publishing date
type
Thesis
publication status
published
subject
keywords
halichomycin, allylation, carbene, hydrogen bond, organozinc, organotitanium, furanosides, organoaluminium, pyranosides, glycosides, stereoselective, endocyclic cleavage, nucleophilic ring opening, ab initio, Organic chemistry, Organisk kemi
pages
53 pages
publisher
Organic Chemistry, Lund University
defense location
Chemical Center
defense date
1998-01-16 10:15
external identifiers
  • Other:ISRN: Lund/NKOK-1038-SE
ISBN
91-628-2763-4
language
English
LU publication?
yes
id
4cb4e8d0-6c46-47ba-8386-2db40f74e80b (old id 29783)
date added to LUP
2007-06-13 11:48:30
date last changed
2016-09-19 08:45:15
@misc{4cb4e8d0-6c46-47ba-8386-2db40f74e80b,
  abstract     = {This thesis is a summary of five papers concerning endocyclic cleavage of glycosides and related acetals. Simple lactol ethers undergo endocyclic cleavage to give acyclic chain extended products on treatment with organoaluminium and organotitanium reagents. The first examples where organotitanium reagents induced alkylative endocyclic cleavage of carbohydrates is presented. The best conditions for the alkylative transfer of a methyl group to benzyl 2-deoxy-2-C-methyl-4-O-(tert-butyldimethylsilyl)-a-D-arabinopyranoside were the application of one equivalent of AlMe3 followed by four equivalents of MeTiCl3 generated by mixing TiCl4 and ZnMe2 2:1, or alternatively, treatment with two equivalents of a mixture of Me2TiCl2 and ZnMe2 1:1. Both yield and diastereoselectivities were comparable with those of the reaction with AlMe3 but titanium reagents were more reactive and could be applied at much lower temperatures than aluminium. A number of pentopyranosides were treated with Me3Al in order to investigate the influence of structural parameters on the methyl group transfer in the endocyclic cleavage reaction of these substrates. Semiempirical and quantum chemical computations indicate that the intermediate formed prior to the selectivity-determing methyl transfer step in the reaction between glycosides and trimethyl aluminium is a strongly hydrogen bonded intermediate wich is proposed to be an important selectivity promoting factor in the alkyl transfer. Combination of Lewis acids and nucleophilic reagents triggered endocyclic cleavage of the furanosidic ring of methyl furanosides resulting in the attachment of the nucleophilic group at C-1 of the carbohydrate. The stereoselectivity in the C-C bond forming step was low for the 2-deoxy furanosides but very high (dr 1:99) for the furanosides carrying a methoxy group in the 2-position when a combination of TiCl4 and ZnMe2 was used. Different selectivities were obtained with ZnMe2 as compared to Me3Al. Reagents based on several organometallic reagents Al, Si, Ti, and Zn in combination with TiCl4. Stereoselective allylation of benzyl pentopyranosides, employing a combination of AlEt2Cl and allyl or crotyl stannane giving a C-7 segment of halichomycin, were investigated.},
  author       = {Olsson, Roger},
  isbn         = {91-628-2763-4},
  keyword      = {halichomycin,allylation,carbene,hydrogen bond,organozinc,organotitanium,furanosides,organoaluminium,pyranosides,glycosides,stereoselective,endocyclic cleavage,nucleophilic ring opening,ab initio,Organic chemistry,Organisk kemi},
  language     = {eng},
  pages        = {53},
  publisher    = {ARRAY(0x906d6a0)},
  title        = {Lewis acid promoted endocyclic cleavage of glycosides and related acetals},
  year         = {1997},
}