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.

Automated summary

Two approaches for preparing terminal alkynes based on enantiomerically pure epimers were established in this study: a non-Wittig route and a Corey-Fuchs approach. The use of n-butyllithium proved to be efficient in both methods. The resulting alkynes were fully characterized, with one used in click chemistry synthesis and observation of atropisomers in another product.