The [3 + 3]-Cycloaddition Alternative for Heterocycle Syntheses: Catalytically Generated Metalloenolcarbenes as Dipolar Adducts

Abstract

ConspectusThe combination of two or more unsaturated structural units to form cyclic organic compounds is commonly referred to as cycloaddition, and the combination of two unsaturated structural units that forms a six-membered ring is formally either a [5 + 1]-, [4 + 2]-, [2 + 2 + 2]-, or [3 + 3]-cycloaddition. Occurring as concerted or stepwise processes, cycloaddition reactions are among the most useful synthetic constructions in organic chemistry. Of these transformations, the concerted [4 + 2]-cycloaddition, the Diels–Alder reaction, is by far the best known and most widely applied. However, although symmetry disallowed as a concerted process and lacking certifiable examples until recently, stepwise [3 + 3]-cycloadditions offer advantages for the synthesis of a substantial variety of heterocyclic compounds, and they are receiving considerable attention.In this Account, we present the development of stepwise [3 + 3]-cycloaddition reactions from virtual invisibility in the 1990s to a rapidly growing synthetic methodology today, involving organocatalysis or transition metal catalysis. With origins in organometallic or vinyliminium ion chemistry, this area has blossomed into a viable synthetic transformation for the construction of six-membered heterocyclic compounds containing one or more heteroatoms. The development of [3 + 3]-cycloaddition transformations has been achieved through identification of suitable and compatible reactive dipolar adducts and stable dipoles. The reactive dipolar species is an energetic dipolar intermediate that is optimally formed catalytically in the reaction. The stepwise process occurs with the reactive dipolar adduct reacting as an electrophile or as a nucleophile to form the first covalent bond, and this association provides entropic assistance for the construction of the second covalent bond and the overall formal [3 + 3]-cycloaddition. Organocatalysis is well developed for both inter- and intramolecular synthetic transformations, but the potential of transition metal catalysis for [3 + 3]-cycloaddition has only recently emerged. The key to the rapid development of the transition metal-based methodology has been recognition that certain catalytically generated vinylcarbenes are effective dipolar adducts for reactions with stable dipolar compounds, including aryl and vinyl ylides. In particular, metallo-enolcarbenes that are generated catalytically from conveniently prepared stable enoldiazoacetates or from donor–acceptor cyclopropenes are highly effective dipolar adducts for [3 + 3]-cycloaddition. The electron-donating oxygen of the silyl ether enhances electrophilic ring closure to the metal-bound carbon of the initial adduct from vinylogous addition, and this enhancement inhibits the alternative [3 + 2]-cycloaddition across the carbon–carbon double bond of the vinylcarbene.Catalytically generated metallo-enolcarbenes react under mild conditions with a broad spectrum of compatible stable dipoles, including nitrones, azomethine imines, ylides, and certain covalent precursors of s...

A bimetallic iridium(ii) catalyst: [{Ir(IDipp)(H)}2][BF4]2 (IDipp = 1,3-bis(2,6-diisopropylphenylimidazol-2-ylidene))

“…[5] The reactivity of bimetallic iridium complexes with substrates such as alkynes, molecular hydrogen, halogens, or halocarbons very often diverges from that of their mononuclear analogues. [6] In the particular case of bimetallic Ir(II) complexes the activation of the substrate may occur by single-site oxidative addition at one of the metal centres.…”

“…[4] The lack of examples of iridium(II) catalysts sharply contrasts with the widespread application of rhodium(II) complexes in catalysis, especially remarkable are the dinuclear catalysts reported by Doyle and coworkers. [5] The reactivity of bimetallic iridium complexes with substrates such as alkynes, molecular hydrogen, halogens, or halocarbons very often diverges from that of their mononuclear analogues. [6] In the particular case of bimetallic Ir(II) complexes the activation of the substrate may occur by single-site oxidative addition at one of the metal centres.…”

The chemistry of the carbon-transition metal double and triple bond: Annual survey covering the year 2014

“…Many articles focusing on some aspect of carbene complex-initiated olefin metathesis were published, including the following specific subjects: (1) the evolution of catalytic stereoselective olefin metathesis [28]; (2) development of cleaner olefin metathesis catalysts [29]; (3) key processes in ruthenium catalyzed olefin metathesis [30]; (4) olefin metathesis in the preparation of active pharmaceutical substances [31]; (5) industrially relevant olefin metathesis catalysts [32]; (6) olefin metathesis in the synthesis of natural products [33]; (7) multi-reaction processes involving Overman rearrangements, metathesis cyclizations, and Diels-Alder reactions [34]; (8) metathesis and polymerization [35]; (9) ROMP of eight-membered ring cyclic olefins [36];…”

“…7, syn isomers were more active; Hoveyda-Grubbs catalysts analogs were also prepared) [163]; (2) indenylidene ligands in place of the benzylidene group and unsymmetrical NHC ligands [164]; (3) a chelating pyridyl alkoxide ligands in place of the phosphine and one chloride ligand [165];…”

“…Tungsten catalysts of general structure 40 were highly effective in promoting Z-selective and stereoregular polymerization of norbornadiene diester derivative 39 [242]. Severally computationally-based studies of olefin metathesis were reported in 2014, including publications that focus on the following topics: (1) the feasibility of iron olefin metathesis catalysts (the pathway involving the iron analog of catalyst 2 is slightly less endothermic than ruthenium catalyst 2) [275,276]; (2) a comparison of various computational techniques (comparison of time and accuracy) for the complete ruthenium-catalyzed olefin metathesis pathway [277]; (3) orbital symmetry in the [2+2] cycloaddition step of olefin metathesis [278]; (4) the electronic effect of various alkylidene groups on the carbon-metal double bond strength (=CH 2 vs =CHF vs =CF 2 ), plus a comparison of Group 8 metals and similar studies on ruthenium metallacyclobutanes using coupled cluster theory [279]; (5) the cross metathesis of propene and styrene focused on the energies and interconversions of metallacyclobutane intermediates [280]; (6) 1-octene self metathesis [281,282]; (7) the ring opening of 3,3-dimethylcyclopropane using W(NH)(CH 2 )(OMe) 2 [283]; (8) olefin metathesis focusing on cis/trans olefin substrate coordination issues [284]; (9) microwave assisted RCM…”