Electronically activated strained alkynes
Compounds of Formula I: wherein: R 1 and R 1′ are independently selected from hydrogen, halogen, C 1 -to-C 12 linear or branched hydroxyalkyl, C 1 -to-C 12 linear or branched halo-alkyl, carboxy, carboxyalkyl, amido, N-alkylamido, N,N-dialkylamido, carbamoyloxy, N-alkylcarbamoyloxy, and N,N-dialkylcarbamoyloxy, provided that that R 1 and R 1′ are not simultaneously hydrogen; R 2 and R 2′ hydrogen, halogen, C 1 -to-C 12 linear or branched hydroxyalkyl, C 1 -to-C 12 linear or branched halo-alkyl, carboxy, carboxyalkyl, amido, N-alkylamido, N,N-dialkylamido, carbamoyloxy, N-alkylcarbamoyloxy, and N,N-dialkylcarbamoyloxy, provided that that R 2 and R 2′ are not simultaneously hydrogen; R 3 is selected from hydrogen, C 1 to C 12 linear or branched alkyl, and nitrogen protecting groups; X is oxygen or nitrogen; when X is oxygen, R 4 is absent; and when X is nitrogen, R 4 is selected from H, C 1 -to-C 12 linear or branched alkyl, and nitrogen protecting groups.
1. A compound of Formula I:
wherein:
R 1 and R 1′ are independently selected from hydrogen, halogen, C 1 -to-C 12 linear or branched hydroxyalkyl, C 1 -to-C 12 linear or branched halo-alkyl, carboxy, carboxyalkyl, amido, N-alkylamido, N,N-dialkylamido, carbamoyloxy, N-alkylcarbamoyloxy, and N,N-dialkylcarbamoyloxy, provided that that R 1 and R 1′ are not simultaneously hydrogen;
R 2 and R 2′ hydrogen, halogen, C 1 -to-C 12 linear or branched alkyl, C 1 -to-C 12 linear or branched hydroxyalkyl, C 1 -to-C 12 linear or branched halo-alkyl, carboxy, carboxyalkyl, amido, N-alkylamido, N,N-dialkylamido, carbamoyloxy, N-alkylcarbamoyloxy, and N,N-dialkylcarbamoyloxy, provided that that R 2 and R 2′ are not simultaneously hydrogen;
R 3 is selected from hydrogen, C 1 to C 12 linear or branched alkyl, and nitrogen protecting groups;
X is oxygen or nitrogen;
when X is oxygen, R 4 is absent; and
when X is nitrogen, R 4 is selected from H, C 1 -to-C 12 linear or branched alkyl, and nitrogen protecting groups.
2. The compound of claim 1 , wherein X is oxygen.
3. The compound of claim 1 , wherein X is nitrogen.
4. The compound of claim 1 , wherein X is oxygen and at least one of R 1 or R 1′ is halogen.
5. The compound of claim 4 , wherein R 1 and R 1′ are halogen.
6. The compound of claim 4 , wherein at least one of R 1 and R 1′ are fluorine.
7. The compound of claim 4 , wherein R 1 and R 1′ are fluorine.
8. The compound of claim 4 , wherein at least one of R 2 and R 2′ is C 1 -to-C 12 linear or branched alkyl or C 1 -to-C 12 linear or branched hydroxyalkyl.
9. The compound of claim 4 , wherein at least one of R 2 and R 2′ is C 1 -to-C 12 linear or branched halo-alkyl.
10. The compound of claim 4 , wherein at least one of R 2 and R 2′ is carboxy or carboxyalkyl.
11. The compound of claim 4 , wherein at least one of R 2 and R 2′ is amido, N-alkylamido, N,N-dialkylamido, carbamoyloxy, N-alkylcarbamoyloxy, or N,N-dialkylcarbamoyloxy.
12. The compound of claim 1 , wherein X is nitrogen and at least one of R 1 or R 1′ is halogen.
13. The compound of claim 12 , wherein R 1 and R 1′ are halogen.
14. The compound of claim 12 , wherein at least one of R 1 and R 1′ are fluorine.
15. The compound of claim 12 , wherein R 1 and R 1′ are fluorine.
16. The compound of claim 12 , wherein at least one of R 2 and R 2′ is C 1 -to-C 12 linear or branched alkyl or C 1 -to-C 12 linear or branched hydroxyalkyl.
17. The compound of claim 12 , wherein at least one of R 2 and R 2′ is C 1 -to-C 12 linear or branched halo-alkyl.
18. The compound of claim 12 , wherein at least one of R 2 and R 2′ is carboxy or carboxyalkyl.
19. The compound of claim 12 , wherein at least one of R 2 and R 2′ is amido, N-alkylamido, N,N-dialkylamido, carbamoyloxy, N-alkylcarbamoyloxy, or N,N-dialkylcarbamoyloxy.
20. The compound of claim 12 , wherein R 4 is H.
21. The compound of claim 12 , wherein R 4 is C 1 -to-C 12 linear or branched alkyl.
22. Compounds of claim 12 , wherein R 4 is a nitrogen protecting group.
23. A method of forming chemical bonds, the method comprising reacting a first compound of Formula I:
wherein:
R 1 and R 1′ are independently selected from hydrogen, halogen, C 1 -to-C 12 linear or branched hydroxyalkyl, C 1 -to-C 12 linear or branched halo-alkyl, carboxy, carboxyalkyl, amido, N-alkylamido, N,N-dialkylamido, carbamoyloxy, N-alkylcarbamoyloxy, and N,N-dialkylcarbamoyloxy, provided that that R 1 and R 1′ are not simultaneously hydrogen;
R 2 and R 2′ hydrogen, halogen, C 1 -to-C 12 linear or branched alkyl, C 1 -to-C 12 linear or branched hydroxyalkyl, C 1 -to-C 12 linear or branched halo-alkyl, carboxy, carboxyalkyl, amido, N-alkylamido, N,N-dialkylamido, carbamoyloxy, N-alkylcarbamoyloxy, and N,N-dialkylcarbamoyloxy, provided that that R 2 and R 2′ are not simultaneously hydrogen;
R 3 is selected from hydrogen, C 1 to C 12 linear or branched alkyl, and nitrogen protecting groups;
X is oxygen or nitrogen;
when X is oxygen, R 4 is absent; and
when X is nitrogen, R 4 is selected from H, C 1 -to-C 12 linear or branched alkyl, and nitrogen protecting groups;
with a second compound comprising a 1,3-dipole, in a 1,3-cycloaddition reaction.