On the electronic effects of OH groups. Synthesis and investigation of tetrahydroxylated azabicycloheptanes

Anette Valentin Gregersen; Christian Marcus Pedersen; Henrik Helligsø Jensen; Mikael Bols

doi:10.1039/b419154d

On the electronic effects of OH groups. Synthesis and investigation of tetrahydroxylated azabicycloheptanes

Anette Valentin Gregersen, Christian Marcus Pedersen, Henrik Helligsø Jensen, Mikael Bols

8 Citationer (Scopus)

Abstract

Two stereoisomeric 2,3,5,6-tetrahydroxyazabicyclo[2.2.1]heptanes were synthesised and their base strengths determined. The 2,3,5,6-exo-isomer 1 and the 2,3-exo-5,6-endo-isomer 2 were prepared from the Diels-Alder adduct of Boc-pyrrole and tosylacetylene by a route involving osmium catalyzed dihydroxylation and protection, tosyl group reduction and repeated dihydroxylation. Deprotection gave 1, while 2 was obtained by conversion of the diol into the ditriflate, followed by nucleophilic inversion with KNO(2) and deprotection. Synthesis of the 2,3,5,6-endo-isomer by a similar strategy was attempted but failed. The pK(a) of 1 and 2 was determined to be 7.0 and 6.4 respectively. This means that the change in base strength as a result of stereoisomerism of an OH is smaller in the [2.2.1]-azabicyclic system than in the piperidines. This is explained by a difference in charge-dipole interactions in the two systems.

Originalsprog	Engelsk
Tidsskrift	Organic & Biomolecular Chemistry
Vol/bind	3
Udgave nummer	8
Sider (fra-til)	1514-1519
Antal sider	6
ISSN	1477-0520
DOI	https://doi.org/10.1039/b419154d
Status	Udgivet - 2005
Udgivet eksternt	Ja

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10.1039/b419154d

Citationsformater

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title = "On the electronic effects of OH groups. Synthesis and investigation of tetrahydroxylated azabicycloheptanes",

abstract = "Two stereoisomeric 2,3,5,6-tetrahydroxyazabicyclo[2.2.1]heptanes were synthesised and their base strengths determined. The 2,3,5,6-exo-isomer 1 and the 2,3-exo-5,6-endo-isomer 2 were prepared from the Diels-Alder adduct of Boc-pyrrole and tosylacetylene by a route involving osmium catalyzed dihydroxylation and protection, tosyl group reduction and repeated dihydroxylation. Deprotection gave 1, while 2 was obtained by conversion of the diol into the ditriflate, followed by nucleophilic inversion with KNO(2) and deprotection. Synthesis of the 2,3,5,6-endo-isomer by a similar strategy was attempted but failed. The pK(a) of 1 and 2 was determined to be 7.0 and 6.4 respectively. This means that the change in base strength as a result of stereoisomerism of an OH is smaller in the [2.2.1]-azabicyclic system than in the piperidines. This is explained by a difference in charge-dipole interactions in the two systems.",

keywords = "Amines, Aza Compounds, Cyclization, Electrons, Heptanes, Hydroxides, Molecular Structure",

author = "Gregersen, {Anette Valentin} and Pedersen, {Christian Marcus} and Jensen, {Henrik Helligs{\o}} and Mikael Bols",

year = "2005",

doi = "10.1039/b419154d",

language = "English",

volume = "3",

pages = "1514--1519",

journal = "Organic & Biomolecular Chemistry",

issn = "1477-0520",

publisher = "Royal Society of Chemistry",

number = "8",

}

TY - JOUR

T1 - On the electronic effects of OH groups. Synthesis and investigation of tetrahydroxylated azabicycloheptanes

AU - Gregersen, Anette Valentin

AU - Pedersen, Christian Marcus

AU - Jensen, Henrik Helligsø

AU - Bols, Mikael

PY - 2005

Y1 - 2005

N2 - Two stereoisomeric 2,3,5,6-tetrahydroxyazabicyclo[2.2.1]heptanes were synthesised and their base strengths determined. The 2,3,5,6-exo-isomer 1 and the 2,3-exo-5,6-endo-isomer 2 were prepared from the Diels-Alder adduct of Boc-pyrrole and tosylacetylene by a route involving osmium catalyzed dihydroxylation and protection, tosyl group reduction and repeated dihydroxylation. Deprotection gave 1, while 2 was obtained by conversion of the diol into the ditriflate, followed by nucleophilic inversion with KNO(2) and deprotection. Synthesis of the 2,3,5,6-endo-isomer by a similar strategy was attempted but failed. The pK(a) of 1 and 2 was determined to be 7.0 and 6.4 respectively. This means that the change in base strength as a result of stereoisomerism of an OH is smaller in the [2.2.1]-azabicyclic system than in the piperidines. This is explained by a difference in charge-dipole interactions in the two systems.

AB - Two stereoisomeric 2,3,5,6-tetrahydroxyazabicyclo[2.2.1]heptanes were synthesised and their base strengths determined. The 2,3,5,6-exo-isomer 1 and the 2,3-exo-5,6-endo-isomer 2 were prepared from the Diels-Alder adduct of Boc-pyrrole and tosylacetylene by a route involving osmium catalyzed dihydroxylation and protection, tosyl group reduction and repeated dihydroxylation. Deprotection gave 1, while 2 was obtained by conversion of the diol into the ditriflate, followed by nucleophilic inversion with KNO(2) and deprotection. Synthesis of the 2,3,5,6-endo-isomer by a similar strategy was attempted but failed. The pK(a) of 1 and 2 was determined to be 7.0 and 6.4 respectively. This means that the change in base strength as a result of stereoisomerism of an OH is smaller in the [2.2.1]-azabicyclic system than in the piperidines. This is explained by a difference in charge-dipole interactions in the two systems.

KW - Amines

KW - Aza Compounds

KW - Cyclization

KW - Electrons

KW - Heptanes

KW - Hydroxides

KW - Molecular Structure

U2 - 10.1039/b419154d

DO - 10.1039/b419154d

M3 - Journal article

C2 - 15827650

SN - 1477-0520

VL - 3

SP - 1514

EP - 1519

JO - Organic & Biomolecular Chemistry

JF - Organic & Biomolecular Chemistry

IS - 8

ER -

On the electronic effects of OH groups. Synthesis and investigation of tetrahydroxylated azabicycloheptanes

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