Pd‐Catalyzed Cycloisomerization of 4‐Aza‐1,6‐enynes to 3‐Aza‐bicyclo[4.1.0]hept‐2‐enes

Abstract

A method for the synthesis of bicyclo[4.1.0]heptenes from 1,6-enynes through Pd-catalyzed cycloisomerization has been developed. N- and O-tethered 1,6-enynes were successfully transformed to their corresponding 3-aza- and 3-oxabicyclo[4.1.0]heptenes in reasonable-to-high yields using the catalysts [PdCl2(CH3CN)2]/P(OPh)3 or [Pd(maleimidate)2(PPh3)2] in toluene. The computational calculations using density functional theory indicate that [PdCl2{P(OPh)3}] in the oxidation state Pd(II) acts as the active catalyst species for the formation of 3-azabicyclo[4.1.0]heptenes through 6-endo-dig cyclization.

Two Divergent Enyne Cycloisomerization Routes Mediated by Monoallenylidene Pd(II) Catalysts

“…When the combination of 3b and AgNTf 2 was utilized, an unusual IMAE reaction, which involved a 6-vinylendo-exo-dig mode cyclization process, took place to provide a series of unexpected six-membered bisalkylidene carbo- or heterocycles. In contrast, the catalyst combination of TAA­(Ph 3 P) 2 -PdCl·BF 4 – 3c and AgNTf 2 would afford bicyclo[4.1.0]­heptane-type cycloisomerization products . This is the first report, to the best of our knowledge, of a new Pd­(II)-mediated IMAE pathway that uses a monoallenylidene–Pd­(II) catalyst.…”

Copper-Promoted Cyclization of α-Amino Nitrile-Tethered Enynes: Controllable Synthesis of 3-Azabicyclo[4.1.0]hepta-2,4-dienes and 4,5-Dihydro-3H-azepines

“…The transition-metal-catalyzed cyclization of enynes offers an attractive pathway for the conversion of relatively simple acyclic substrates to a variety of valuable cyclic compounds which have been difficult to prepare by conventional methods . Recently, the versatile cyclization chemistry of enynes has made possible the construction of valuable functional bicyclo[4.1.0]­alkene frameworks by means of transition-metal catalysts. ,,, Typically, the presence of electron rich C–C double bond component is to be pivotal to the accomplishment of this electrophilic activation-involved transformation in which the N, O, or C atom bridged the C–C triple bond and double bond units (Scheme a), while the cyclization of enynes incorporating an electronically deficient C–C double bond proved to be challenging and has been never reported. On the other hand, this type of catalytic cyclization was dominated by Pt, Au, Ir, and Rh catalysts, while other lower cost metal catalyzed cyclizations are rare.…”

“…Recently, the versatile cyclization chemistry of enynes has made possible the construction of valuable functional bicyclo[4.1.0]­alkene frameworks by means of transition-metal catalysts. ,,, Typically, the presence of electron rich C–C double bond component is to be pivotal to the accomplishment of this electrophilic activation-involved transformation in which the N, O, or C atom bridged the C–C triple bond and double bond units (Scheme a), while the cyclization of enynes incorporating an electronically deficient C–C double bond proved to be challenging and has been never reported. On the other hand, this type of catalytic cyclization was dominated by Pt, Au, Ir, and Rh catalysts, while other lower cost metal catalyzed cyclizations are rare. Fehr et al disclosed an elegant copper-catalyzed cyclization of enyne including a propargylic alcohol moiety to construct a bicyclo[3.1.0]­hexene framework, but with a limited substrate scope (Scheme a) .…”