Microwave-Assisted Heck Arylations of Non-ActivatedN-Acyl-3-pyrrolines with Arenediazonium Tetrafluoroborates

Synthesis of 3-Substituted Pyrrolidines via Palladium-Catalyzed Hydroarylation

“…The Mizoroki-Heck (MH) reaction ( Braese and de Meijere, 2014 , Oestreich, 2009 ) was one of the earliest reported method ( Mizoroki et al., 1971 , Heck and Nolley, 1972 ) to execute direct, substoichiometric catalytic modification of simple alkenes; for cycloalkenes, the MH reaction proceeds by overall functionalization of an sp 3 —rather than an sp 2 —CH bond, due to the stereoelectronic control for β-hydride elimination in the key palladium(II) intermediates 1 ( Figure 2 A). In addition to the parent cycloalkene systems, the reaction can be applied to 2,3-dihydropyrans ( Mata et al., 2007 , Wu and Zhou, 2014 ) ( 2 , X=O) and the analogous N-carbamoyl pyrrolines ( Sonesson et al., 1996 , Carpes and Correia, 2002 , Montes de Oca and Correia, 2003 , Garcia et al., 2005 , Peixoto da Silva et al., 2007 , Finelli et al., 2015 ) ( 2 , X=N–C[O]R) ( Figure 2 ), but the reactions can be unpredictable (cf. Figures 2 A and 2B).…”

Synthesis of 3-Substituted Pyrrolidines via Palladium-Catalysed Hydroarylation

“…The Mizoroki-Heck ('MH') reaction 17,18 was the first reported method 19,20 to execute direct, substoichiometric catalytic modification of simple alkenes; for cycloalkenes, the MH reaction proceeds by overall functionalization of an sp 3 -rather than an sp 2 -CH bond, due to the stereoelectronic control for b-hydride elimination in the key palladium(II) intermediates 1 ( 5HT 6 and D 3 K i = 1-10 nM K i (D 2 )/K i (D 3 ) >150 11 PARP10 IC 50 = 780 nM 10 hGlyT1 K i = 17 nM 9 HDAC1 IC 50 = 60 nM 8 LdKMT K i = 63 nM 7 D 3 K i = 90 pM 13 D 2 K i = 68 nM D 3 K i = 52 nM 2a). In addition to the parent cycloalkene systems, the reaction can by applied to 2,3dihydropyrans 21,22 (2, X=O) and the analogous N-acyl pyrrolines 23,24,25,26,27,28 (2, X=N-C[O]R) ( Figure 2), but the reactions can be unpredictable (cf. Figure 2a and 2b).…”

“…PARP10 IC 50 = 780 nM 10 hGlyT1 K i = 17 nM 9 HDAC1 IC 50 = 60 nM 8 LdKMT K i = 63 nM 7 D 3 K i = 90 pM 13 D 2 K i = 68 nM D 3 K i = 52 nM 2a). In addition to the parent cycloalkene systems, the reaction can by applied to 2,3dihydropyrans 21,22 (2, X=O) and the analogous N-acyl pyrrolines 23,24,25,26,27,28 (2, X=N-C[O]R) (Figure 2), but the reactions can be unpredictable (cf. Figure 2a and 2b).…”