Cobalt‐Catalyzed Alder–Ene Reaction

Abstract

A valuable preparative synthetic method is characterized by a broad scope of substrates and high chemo-and regioselectivity in combination with an excellent yield. Many prominent transition-metal-catalyzed reactions, such as the Grubbs olefin metathesis [1] or the Sharpless epoxidation or bishydroxylation [2] fulfill these criteria. Recently we reported the cyclotrimerization of alkynes with simple cobalt-diimine complexes.[3] During this work we found that cobalt-diphosphine complexes, such as [Co-(dppe)Br 2 ], which we successfully applied in the cobaltcatalyzed Diels-Alder reaction of non-activated starting materials, did not efficiently catalyze the cyclotrimerization of terminal alkynes to form the aromatic product 1 (Scheme 1). The transformation of internal alkynes to the corresponding aromatic products could only be realized in acceptable yields at elevated temperatures and prolonged reaction times.Clearly, these results indicate that the starting materials coordinate to the cobalt center and that the desired cyclotrimerization proceeds; however, with internal alkynes the C À C coupling step is relatively slow. Therefore, under milder reaction conditions the coordination of alkynes should still be possible while the reaction rate for the cyclotrimerization should be further reduced. Additional substrates could then be added leading to alternative reaction pathways and new products. Thus, in addition to the internal alkynes, terminal alkenes were added to the catalyst. The outcome of this reaction was a formal intermolecular Alder-ene reaction [4] (Scheme 2) to afford the 1,4-diene 4. This reaction is mechanistically related to the transformations undertaken by Trost with the [CpRu] + (Cp = C 5 H 5 ) fragment.[5] Therefore, the cobalt-catalyzed reaction could also involve the coordination of the two starting materials in the coordination sphere of the cobalt center to form the cobaltacycle 2 (Scheme 2). A b-hydride elimination to 3 and a reductive elimination complete the stepwise formal Alder-ene reaction under very mild reaction conditions.Over the course of the investigation we realized that the transformation with a cobalt-dppm complex was very slow. Good results had already been obtained with a cobalt-dppe [6] complex, whereas the best results to date were with a cobaltdppp [6] catalyst system. When a longer carbon chain was used in the diphosphine ligand, such as dppb, [6] the activity of the cobalt complex was reduced considerably, thus for further investigations the dppp ligand was used.Some questions arise for this atom-economic interconnection of two simple starting materials: a) is the cobalt catalyzed Alder-ene reaction applicable to terminal alkynes? b) can unsymmetrical alkynes be transformed regioselectively? c) can the stereochemistry of the two newly formed double bonds in the 1,4-diene be controlled by the catalyst? and d) are a wide variety of functional groups accepted by the cobalt catalyst?The first question could be answered easily: terminal alkynes prefer the formation of the cycl...

Cobalt‐ and Nickel‐Catalyzed Regio‐ and Stereoselective Reductive Coupling of Alkynes, Allenes, and Alkenes with Alkenes

“…Very recently, Hilt and Treutwein reported a cobalt-catalyzed intermolecular coupling (Alder-ene reaction) of unactivated alkenes with alkynes (Scheme 7). [9] In the reaction, Under similar reaction conditions, enals 25 reacted with alkynes 6 to give [3+2] cycloaddition products, cyclopentanol derivatives, 26 in good to excellent yields with high diastereoselectivity (Scheme 8). [10b] The catalytic reaction proceeds through chemoselective coordination of an alkyne and alkene to the Ni 0 center followed by regioselective oxidative cyclometalation with the assistance of MeOBEt 2 yielding nickelacycle intermediate 27 (Scheme 9).…”

Catalytic Enantioselective Synthesis of Cyclobutenes from Alkynes and Alkenyl Derivatives

“…In this regard, a class of compounds with enormous potential for diversification are the chiral 3-substituted cyclobutenes (Figure 1, B), which allow further modification of the small ring through a myriad of ways involving the double bond, 7 the G group, 8 or through activation of the ring C-H bonds. 9 The simplest approach to making cyclobutenes is through an enantioselective [2+2]- cycloaddition between an alkyne and an alkenyl derivative, a reaction with a long history, starting with mostly addition of reactive alkynes to bicyclic 10 or activated 11 alkenes with the notable exceptions of additions of activated alkynes to cyclopentene (Hilt) 12a and a variety of styreneyl alkenes to enynes (Ogoshi), 12b both giving racemic products. Thus, there are no examples in the literature of a broadly applicable enantioselective version of this [2+2]-cycloaddition process.…”

Biorelevant Metals in Sustainable Metal Catalysis—A Survey

“…Hilt reported an important improvement in the field of cobalt catalysis by reducing a stable Co II precatalyst with zinc powder. The catalyst that was generated under these conditions catalyzed, for example, the Alder‐ene reaction, which was believed to follow a mechanism similar to that of cycloaddition reactions (Scheme ) 243. This protocol provides a highly atom‐economic approach to substituted 1,4‐dienes with good chemo‐ and regioselectivities.…”