Asymmetric synthesis of vinylepoxides, vinylaziridines and vic-amino alcohols
- A Regio- and Stereodivergent Route to All Isomers of vic -Amino Alcohols
The aim of the project was to develop a synthetic strategy that provided all eight possible isomers of a given vic-amino alcohol starting from vinylepoxides. The value of a general route is evident, as several isomers are needed in investigations of structure-activity relationships for pharmacologically active derivatives, and for optimizing the performance of chiral ligands containing the amino alcohol moiety. The strategy was successfully developed, and resulted in 7 papers describing both methodology and applications, as detailed below.
A set of vinylepoxides 1 was synthesized with high enantiomeric excess. Subsequent diastereoselective ring-opening with both inversion and retention of stereochemistry delivered the two diastereomeric amino alcohols 2 and 3 with high regio- and diastereoselectivity.
Via ring-closure to aziridines 4 and subsequent regioselective ring-opening with suitable oxygen nucleophiles, the two remaining amino alcohols 5 and 6 were selectively obtained.1-3
Within this study, two efficient protocols for the regioselective and stereospecific aminolysis of vinylepoxides have been presented. Compared to previous methods, these procedures use milder reaction conditions, shorter reaction times, generally give higher yields and are applicable to a larger set of substrates.3,4
Furthermore, the ring-closure of vic-amino alcohols 2 to the corresponding N-H vinylaziridines 4 was investigated. Three routes were found useful, which one is preferred depends on substrate and scale.5
Finally, the synthetic strategy was applied to the synthesis of Sphingosine and its regio- and diastereoisomers.6 Moreover, a rapid way of determining the relative configuration of vic-amino alcohols was described, which should be of substantial use when amino alcohols are formed by diastereoselective reactions.7
1. B. Olofsson, U. Khamrai, P. Somfai: "A Regio- and Stereodivergent Synthesis of vic-Amino Alcohols" Org. Lett. 2000, 2, 4087-4089. PDF
2. B. Olofsson, P. Somfai: "A Regio- and Stereodivergent Route to all Isomers of vic-Amino Alcohols" Latvias J. Chem. 2002, 1, 69-78. PDF
3. B. Olofsson, P. Somfai: "Divergent Synthesis of D-erythro-Sphingosine, L-threo-Sphingosine and their Regioisomers" J. Org. Chem. 2003, 68, 2514-2517. PDF
4. U. M. Lindström, B. Olofsson, P. Somfai: "Microwave-Assisted Aminolysis of Vinylepoxides" Tetrahedron Lett. 1999, 40, 9273-9276. PDF
5. B. Olofsson, R. Wijtmans, P. Somfai: "Synthesis of N-H Vinylaziridines: A Comparative Study" Tetrahedron 2002, 58, 5979-5982. PDF
6. B. Olofsson, P. Somfai: "A Regio- and Stereodivergent Route to all Isomers of vic-Amino Alcohols" J. Org. Chem. 2002, 67, 8574-8583. PDF
7. B. Olofsson, P. Somfai: "Determination of the Relative Configuration of vic-Amino Alcohols" Tetrahedron Lett. 2003, 44, 1279-1281.PDF