Synthesis of terminal alkynes based on (1S,3R,4R)- and (1S,3S,4R)-2-azabicyclo[2.2.1]heptane

Two approaches to terminal alkynes based on the enantiomerically pure epimers (1S,3R,4R)- and (1S,3S,4R)-2-azabicyclo[2.2.1]heptane aldehydes were established: i) a non-Wittig route through a dichloroalkene intermediate; and, ii) a Corey-Fuchs approach via dibromoalkene. Among various organometallic reagents tested, the use of n-butyllithium was efficient. The resulting alkynes were fully characterized, and one epimer was used in a click chemistry triazole synthesis. For one of the products containing a bulky N-Boc-proline substituent, the existence of atropisomers was observed. The absolute stereochemistry was determined by electronic circular dichroism spectroscopy (ECD) and optical rotation supported by quantum chemical simulations.