Domino Carbopalladation‐Carbonylation: Investigation of Substrate Scope

Abstract

This work gives an in depth account of our domino carbopalladation-carbonylation method for substrates possessing b-hydrogens. The scope of the method is examined for allylic amines containing trisubstituted olefins and we detail our attempts toward the diastereospecific synthesis of contiguous quaternary centers using this technology. The results give key insights into the relative rates of the competing reactions of the alkyl palladium intermediates, which is crucial for the understanding and development of new domino processes.

Manganese-Catalyzed Carboacylations of Alkenes with Alkyl Iodides

“…3 We became interested in pursuing an alternative process involving alkene difunctionalization (carboacylation). 4 Prior to our studies there was limited precedent for this class of alkene difunctionalization; a photochemical palladium-catalyzed carboacylation has been reported, but requires excess alkyl iodide (1.5 equiv) and was limited to ketone synthesis using alkyl-boranes. 5 …”

Pd-Catalyzed Highly Regio- and Stereoselective Formation of C–C Double Bonds: An Efficient Method for the Synthesis of Benzofuran-, Dihydrobenzofuran-, and Indoline-Containing Alkenes

“…On the other hand, the intramolecular carbometalation of alkenes [35][36][37][38][39][40][41][42][43][44][45][46][47][48] initiated from the oxidative addition of C(sp 2 )-X provides an efficient method to construct benzo-fused saturated nitrogen/oxygen heterocycles such as indolines [35][36][37][38][39][40] and dihydrobenzofurans, [41][42][43][44][45][46][47][48] which are prominent in a variety of natural products and biologically active compounds. [49][50][51][52][53][54][55] In 2002, Grigg and co-workers reported an interesting Pd-catalyzed queuing processes by employing allene as a relay switch and secondary amines as nucleophiles.…”

“…On the other hand, the intramolecular carbometalation of alkenes − initiated from the oxidative addition of C­(sp 2 )–X provides an efficient method to construct benzo-fused saturated nitrogen/oxygen heterocycles such as indolines − and dihydrobenzofurans, − which are prominent in a variety of natural products and biologically active compounds. − In 2002, Grigg and co-workers reported an interesting Pd-catalyzed queuing processes by employing allene as a relay switch and secondary amines as nucleophiles . Inspired by these precedents and our continued interest in the palladium-catalyzed cross-coupling of N -tosylhydrazones, − we conceived that the alkyl-Pd species generated from intramolecular carbopalladation of alkene may be trapped by a diazo substrate to form a Pd carbene species, which would undergo migratory insertion and β-hydride elimination to afford the polysubstituted olefins (Scheme c).…”

Constructing chiral bicyclo[3.2.1]octanes via palladium-catalyzed asymmetric tandem Heck/carbonylation desymmetrization of cyclopentenes

“…T ransition-metal (TM)-catalyzed carbonylation reaction [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] , especially palladium-catalyzed tandem Heck/carbonylation reaction, presents an efficient method to construct a variety of synthetically versatile carbonyl compounds from readily accessible organic halides and alkenes [17][18][19][20][21] . Moreover, these methods have been applied as key steps in the total synthesis of natural products and bioactive molecules [22][23][24][25][26][27][28] .…”