Palladium(0)‐Catalyzed Alkynyl and Allenyl Iminium Ion Cyclizations Leading to 1,4‐Disubstituted 1,2,3,6‐Tetrahydropyridines

Abstract

The biologically important title heterocyclic compounds can be synthesized by two methods based on the cyclization of alkynyl and allenyl iminium ions generated in situ in the presence of organometallic reagents (see scheme). Symmetrical and unsymmetrical tetrahydropyridines with diverse substituents R4 were prepared in a single step under mild conditions. R1=n‐, sec‐, tert‐alkyl; R4=aryl, 1‐alkenyl, alkyl, 1‐alkynyl, B(pinacolato).

Enantioselective Nickel-Catalyzed anti-Carbometallative Cyclizations of Alkynyl Electrophiles Enabled by Reversible Alkenylnickel E/Z Isomerization

“…5 However, if syn -carbometalation proceeds to place the metal distal to the electrophile (as in II ), cyclization is not possible due to geometric constraints (Figure 1C). 6 An anti -carbometalation of the alkyne would provide a solution to this problem, as now the resulting alkenylmetal species III possesses the correct geometry for cyclization (Figure 1C). However, overcoming the inherent syn -selectivity of alkyne migratory insertion is a considerable challenge.…”

“…As well as demonstrating the ability of nickel catalysis to provide anti -carbometalation products from alkynes that do not contain a tethered electrophile, this experiment suggests that the domino reactions described herein proceed through a mechanism similar to that shown in Figure 1C, rather than one involving initial “ anti -Wacker-type” additions. 6 The reaction of 1-phenyl-1-butyne with 2-formylphenylboronic acid using L7 as the chiral ligand (see Table 1, entry 8 for the use of L7 in anti -carbometallative cyclization) gave indene 10 in 81% yield and 87% ee (eq 2), which is a product of syn -arylnickelation of the alkyne followed by cyclization of the resulting alkenylnickel species onto the aldehyde. 13 The ability to obtain enantioenriched products from either syn - or anti -carbometallative cyclization illustrates the adaptive power of this nickel-based catalytic system and further suggests that reversible E / Z isomerization of alkenylnickel species is operative.…”

Amines as key building blocks in Pd-assisted multicomponent processes

“…Tsukamato extended this methodology further to the cyclization of alkynyl- and allenyliminiums in order to access 1,4-disubstituted-1,2,3,6-tetrahydropyridines 15 or 16 following the same strategy [ 7 ]. For alkynyliminiums, two different catalytic systems were developed according to the nature of the aryl- or heteroarylboronic acids used.…”

C–H amination/cyclocarbonylation of allene carbamates: a versatile platform for the synthesis of α,β-unsaturated γ-lactams

“…Certainly, the chemoselectivity in intramolecular allylic aminations of acyclic substrates has been demonstrated to be unpredictable. 15,16 Du Bois has reported surprising chemoselectivity in allylic CeH bond insertions of homoallyl sulfamates using a Rh 2 (S-nap) 4 catalyst, although the reasons for this selectivity are not well-understood. 15 We observed a similar effect in our early studies directed toward new, efficient methods for the stereoselective functionalization of all three carbons of an allene.…”

“…4 , ceric ammonium nitrate, and phosphomolybdic acid in ethanol stain.1 H NMR and 13 C NMR spectra were obtained using Bruker-300, OD, respectively) 13. C NMR spectra were measured at either 125 MHz or 150 MHz on the same instruments noted above for recording 1 H NMR spectra.…”