Advances in Palladium‐Catalyzed Cascade Cyclizations

Abstract

Thep ast decades in organic chemistry have witnessed significant improvements in synthetic efficiency as ar esult of considerable progress in cascade reactions,t andem reactions,a nd related onepot processes. These methods are less time-consuming andp roduce less waste comparedt ot he classical stepwise approach. However, cascade chemistry requires am ore careful design and compatible reaction types for success.P alladium-catalyzed cross-coupling reactions,w ith their well understoodm ultistep catalytic cycles,f orm ap romising basis for the design of cascade reactions.F urthermore,t hey are compatible with ar ange of functional groups and can be combined with ar ange of secondary transformations. Ther esulting palladium-catalyzed cascade reactions have provided access to ap lethorao fc omplex small molecules of high medicinal relevance.T his review providesa no verview of the developments in palladium-catalyzed cascade reactions since 2011, classified according to the initiation, propagation, andtermination steps comprising the palladium cascade reactions.T hisc lassification should assist the reader and may provide inspiration for the design of newc ascade reactions.

Palladium‐Catalyzed Cascade Cyclization/Alkynylation Reactions

“…For instance, In 2016, Werz and co‐workers reviewed the carbopalladation cascade protocols of alkynes for the synthesis of various high added‐value heterocyclic scaffolds . Recently, Ruijter and Biemolt also elucidated the palladium‐catalyzed cascade cyclizations/functionalization reaction involving alkynes …”

Pd‐Catalyzed Annulation of β‐Iodovinyl Sulfones with 2‐Halophenols: A General Route for the Synthesis of 3‐Sulfonyl Benzofuran Derivatives

“…Based on the above experimental results and the literature precedent, a plausible mechanism for this tandem process is proposed (Scheme ). Firstly, base‐promoted oxa‐Michael addition of β‐iodovinyl sulfone ( 1 a ) with 2‐bromophenol 2 a could form enol ether ( E ‐ 3 a ).…”

“…Thus, it was assumed the coordination of palladium to alkene moiety through π-system complexation may allow partial isomerization (Z to E) (see the Supporting Information). [20] Moreover, the reaction between alkynyl sulfone (7) [17b] and 2-bromophenol 2 a under the same conditions, unsuccessful to provide 3 a or 3 aa (Scheme 7d). Further, we have successfully prepared the desired deuterated starting material 1 a-D (98%-d) to perform isotopic experiments (see the Supporting Information).…”

“…To our surprise, the desired benzofuran 3 aa was formed in 13% yield. Thus, it was assumed the coordination of palladium to alkene moiety through π‐system complexation may allow partial isomerization ( Z to E ) (see the Supporting Information) . Moreover, the reaction between alkynyl sulfone ( 7 ) and 2‐bromophenol 2 a under the same conditions, unsuccessful to provide 3 a or 3 aa (Scheme d).…”

“…The intra‐molecular coordination with olefin moiety via π‐bond complexation to form the intermediary ( B ) . Subsequent carbopalladation process generates the organo‐palladium species ( C ) followed by β‐hydride elimination lead to desired product 3 aa and active palladium(0)catalyst would be regenerated in the presence of base for the further catalytic process.…”