Synthesis of Polysubstituted Olefins by Pd-Catalyzed Cross-Coupling Reaction of Tosylhydrazones and Aryl Nonaflates

Abstract

Aryl nonaflates are employed as electrophiles in the Pd-catalyzed cross-coupling with tosylhydrazones affording di-, tri-, and tetrasubstituted olefins. Fine tunning of the reaction conditions are required to accomplish the coupling successfully, including the addition of LiCl and the presence of small amounts of water. Under the optimized conditions, the reactions proceed with high yield and also high stereoselectivity depending on the nature of the coupling partners.

Synthesis of (Z)‐N‐Alkenylazoles and Pyrroloisoquinolines from α‐N‐Azoleketones through Pd‐Catalyzed Tosylhydrazone Cross‐Couplings

“…In a preliminary experiment, we studied the coupling reaction between tosylhydrazone 3 a , obtained from α‐ N ‐indoleacetophenone 1 a , with ortho ‐methoxybenzene nonaflate ( 2 a ; Scheme ). After some experimentation, we found that, under reaction conditions similar to those previously reported for the coupling of other classes of tosylhydrazone with aryl nonaflates,4, 5a the trisubstituted alkene 4 a could be obtained in high yield. As expected, the Z isomer was obtained as the major isomer in very high stereoselectivity.…”

“…The last step defines the stereochemistry of the final product. With the aid of DFT computations, it has been determined that, to avoid steric interactions, the optimal arrangement for the transition state of the syn ‐β‐hydride elimination places the R substituent on the same side of the incipient double bond as the ortho ‐substituted arene 5a…”

Highly Selective β‐Hydride Elimination in the Pd‐Catalyzed Cross‐Coupling of N‐Tosylhydrazones with Benzyl Bromides

“…Despite this progress, a strategic choice of coupling partners is necessary to control regioselectivity, which limits the scope of these transformations. For example, when aryl halides were used as electrophiles, blocking of one of the two β ‐positions in carbonyl‐ derived nucleophiles was required to avoid the competitive reactions (Scheme , R 1 =Aryl,, H, CF 3 , Alkenyl, Acyl, etc …”

Palladium‐Catalyzed Allylic Arylation of Allylic Ethers with Arylboronic Acids Using Hydrazone Ligands

“…1‐Methyl‐2‐(3‐phenyl‐1‐propen‐1‐yl)benzene (3p): 10 93 % as a colorless oil. 1 H NMR (300 MHz, CDCl 3 ): δ = 7.40–7.44 (m, 1 H), 7.12–7.34 (m, 8 H), 6.66 (d, J = 15.6 Hz, 1 H), 6.23 (dt, J = 15.6 and 6.9 Hz, 1 H), 3.57 (d, J = 6.9 Hz, 2 H), 2.34 (s, 3 H) ppm.…”