A Facile Synthesis of Lentiginosine Analogues Based on a Highly Regio‐ and Diastereoselective Allylic Amination Using Chlorosulfonyl Isocyanate
The concise synthesis of the lentiginosine analogues pyrrolizidine alkaloid 2 and pyrroloazepine alkaloid 3 has been achieved from inexpensive and readily available D -lyxose. The key steps in the synthesis included regio- and diastereoselective amination, inter- or intramolecular olefin metathesis, and Appel cyclization. The anti-3,4-amino alcohol 6, essential for the preparation of the title compounds 2 and 3, was synthesized by the regio- and diastereoselective amination of anti-3,4-tribenzyl ether 7 using chlorosulfonyl isocyanate. The reaction of 7 with chlorosulfonyl isocyanate in toluene at 0 °C afforded 6 exclusively with a diastereoselectivity of 26:1 in 84 % yield. These results can be explained by the neighboring-group effect, which leads to retention of the stereochemistry.