Cycloaddition Reactions of Cobalt-Complexed Macrocyclic Alkynes: The Transannular Pauson–Khand Reaction

Abstract

The Pauson-Khand reaction is a powerful tool for the synthesis of cyclopentenones through the efficient [2 + 2 + 1] cycloaddition of dicobalt alkyne complexes with alkenes. While intermolecular and intramolecular variants are widely known, transannular versions of this reaction are unknown and the basis of this study. Macrocyclic enyne and dienyne complexes were readily synthesized by palladium(II)-catalyzed oxidative macrocyclizations of bis(vinyl boronate esters) or ring-closing metathesis reactions followed by complexation with dicobalt octacarbonyl. Several reaction modalities of these macrocyclic complexes were uncovered. In addition to the first successful transannular Pauson-Khand reactions, other intermolecular and transannular cycloaddition reactions included intermolecular Pauson-Khand reactions, transannular [4 + 2] cycloaddition reactions, intermolecular [2 + 2 + 2] cycloaddition reactions, and intermolecular [2 + 2 + 1 + 1] cycloaddition reactions. The structural and reaction requirements for each process are presented.

Recent Developments in Transannular Reactions

“…Finally, there is one example of a transannular Pauson–Khand reaction described in the literature that has been carried out on a macrocyclic dicobalt enyne complex (Scheme 49 ). 74 The reaction employed an excess of N -methylmorpholine N -oxide (NMO) as promotor to activate the loss of a carbonyl group form the cobalt complex and also had to be conducted under highly diluted conditions in order to avoid intermolecular byproducts. The starting material was employed as a 2.5:1 mixture of cis / trans diastereomers, retaining the diastereomeric ration on the final Pauson–Khand product.…”

Gold Self‐Relay Catalysis Enabling [3,3]‐Sigmatropic Rearrangement/Nazarov Cyclization and Allylic Alkylation Cascade for Constructing All‐Carbon Quaternary Stereocenters

“…Moreover, this skeleton could serve as a powerful intermediate to synthesize some natural products and pharmaceuticals [ 6‐8 ] due to the wide diversity of potential functionalizations at the enone unit. As such, great efforts have been made over the last decades to establish state‐ of‐art and reliable methods for the fabrication of such scaffolds, which mainly include Pauson−Khand reactions, [ 9‐13 ] Nazarov cyclizations, [ 14‐18 ] Rautenstrauch Rearrangements, [ 19‐21 ] organocatalyzed reactions, [ 22‐25 ] functionalizations of the existing cyclopentenone unit [ 26‐27 ] as well as cyclization of acyclic substrates. [ 28‐34 ] Despite these remarkable achievements, the continuous development of new synthetic approaches for assembling functionalized cyclopentenones would be particularly useful, given their potential application and pharmaceuticals.…”

Trimacrocyclic hexasubstituted benzene linked by labile octahedral [X(CHCl3)6]− clusters

“…One way to overcome this latter energic penalty is to reduce the degrees of freedom by means of macrocyclization so as to generate, e.g., trimacrocyclic hexasubstituted benzene (THB) derivatives. 33,34 Taking advantage of this latter strategy we have now prepared a trimacrocyclic hexasubstituted benzene 2 receptor wherein crown ethers are incorporated into the system (Fig. 2a).…”