Lewis Acid Mediated Vinyl‐Transfer Reaction of Alkynes to N‐Alkylimines by Using the N‐Alkyl Residue as a Sacrificial Hydrogen Donor

Abstract

A variety of N-alkyl-α,α-dichloroaldimines were vinylated by terminal acetylenes in the presence of Lewis acids such as In(OTf)3 or BF3 ⋅OEt2 and hexafluoroisopropanol (HFIP) as an additive. The reaction proceeds at ambient temperature and leads to geometrically pure allylic β,β-dichloroamines. This approach is complementary to previously reported transition-metal-catalyzed vinyl-transfer methods, which are not applicable to aliphatic imines and are restricted to imines that contain an electron-withdrawing nitrogen substituent. In the present approach, terminal alkynes were used as a source of the vinyl residue, and the N-alkyl moiety of the imine acts as a sacrificial hydrogen donor. The additional advantage of this methodology is the fact that no external toxic or hazardous reducing agents or molecular hydrogen has to be used. This new methodology nicely combines a C(sp(2) )C(sp) bond formation, hydride transfer, and an unusual cleavage of an unactivated CN bond, thereby giving rise to functionalized primary allylic amines. A detailed experimental study supported by DFT calculations of the mechanism has been done.

HFIP in Organic Synthesis

“…A Lewis acid-mediated vinylation of N -alkyl-α,α-dichloroaldimines by terminal alkynes as a vinyl source afforded geometrically pure ( E )-allylic β,β-dichloroamines (Scheme ). Indium­(III) triflate (In­(OTf) 3 ) and BF 3 •OEt 2 were effective catalysts in 9:1 DCM/HFIP. The use of 9:1 phenol/TFE was less effective.…”

Einfluss der Nachbehandlung auf das Karbonatisierungsverhalten von Beton aus klinkerarmen Zementen

“…Electron‐rich acetylenes even reacted with imines 1g–m , having an α ′‐H at the N ‐substituent (R 2 =Pr, i‐ Pr, benzyl) and gave rise to the corresponding amino ketones 3 and 5 in good yields. The vinylated products, which were observed earlier under In(OTf) 3 or BF 3 ⋅OEt 2 conditions in CH 2 Cl 2 /HFIP (9/1),14 were not observed in pure HFIP. Phenylacetylene ( 2a ), reacted smoothly with imines 1a (R 1 =Me) and 1b , (R 1 =Cl), while imine 1e (R 1 =pentyl) did not yield any reaction product.…”

“…In 2012, our group reported the synthesis of β,β‐dichloropropargylic amines from the reaction of α,α‐dichloroaldimines and terminal acetylenes using In(OTf) 3 as Lewis acid in CH 2 Cl 2 at 50 °C 13. However, when the same α,α‐dichloroaldimines were reacted with terminal acetylenes using either In(OTf) 3 or BF 3 ⋅OEt 2 in CH 2 Cl 2 /HFIP (9/1) as solvent system, allylic β,β‐dichloroamines were obtained 14. Since this process involves a β‐hydride elimination mechanism, the presence of at least one hydrogen on the α′‐carbon of the N ‐alkyl residue was mandatory for this vinylation 14.…”

“…However, when the same α,α‐dichloroaldimines were reacted with terminal acetylenes using either In(OTf) 3 or BF 3 ⋅OEt 2 in CH 2 Cl 2 /HFIP (9/1) as solvent system, allylic β,β‐dichloroamines were obtained 14. Since this process involves a β‐hydride elimination mechanism, the presence of at least one hydrogen on the α′‐carbon of the N ‐alkyl residue was mandatory for this vinylation 14. Clearly, HFIP directs the reaction of alkynes with N ‐alkylimines to different reaction products.…”

HFIP-Empowered One-Pot Synthesis of C4-Aryl-Substituted Tetrahydroquinolines with Propargylic Chlorides and Anilines

“…With its strong hydrogen bonding ability, HFIP promotes functionalization of C–X, C–O, CO, CN, CC, and even C–H bonds with a metal catalyst, to form new C–C or C–N bonds effectively (Scheme ). For example, vinyl transfer of alkynes to aldimines occurred in the presence of HFIP . Recently, C -alkylation of anilines with unreactive styrenes was enabled by employing HFIP …”