Citation for published version: Provis-Evans, C, Lau, S, Krewald, V & Webster, R 2020, 'Regioselective Alkyne Cyclotrimerization with an In Situ-Generated [Fe(II)H(salen)]·Bpin Catalyst', ACS Catalysis, vol. 10, no. 17, pp. 10157–10168. https://doi.org/10.1021/acscatal.0c03068 DOI: 10.1021/acscatal.0c03068 Publication date: 2020 Document Version Peer reviewed version Link to publication This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Catal., copyright © American Chemical Society after peer review and technical editing by the publisher. 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Oct. 2021 Subscriber access provided by The Library | University of Bath Article Regioselective Alkyne Cyclotrimerization with an In Situ-Generated [Fe(II)H(salen)]·Bpin Catalyst Cei Benjamin Provis-Evans, Samantha Lau, Vera Krewald, and Ruth L Webster ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.0c03068 • Publication Date (Web): 07 Aug 2020 Downloaded from pubs.acs.org on August 12, 2020 Just Accepted “Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted online prior to technical editing, formatting for publication and author proofing. The American Chemical Society provides “Just Accepted” as a service to the research community to expedite the dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been fully peer reviewed, but should not be considered the official version of record. 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However, no copyright claim is made to original U.S. Government works, or works produced by employees of any Commonwealth realm Crown government in the course of their duties. Page 1 of 27 ACS Catalysis 1 2 3 4 5 6 7 Regioselective Alkyne Cyclotrimerization with an In Situ-Generated 8 9 [Fe(II)H(salen)]·Bpin Catalyst 10 † † ,‡ ,† 11 Cei B. Provis-Evans, Samantha Lau, Vera Krewald,* and Ruth L. Webster* 12 †Department of Chemistry, University of Bath, Claverton Down, Bath BA2 7AY, United Kingdom 13 ‡ 14 Department of Chemistry, Theoretical Chemistry, TU Darmstadt, Alarich-Weiss-St. 4, 64287 Darmstadt, Germany 15 16 ABSTRACT: A mild, efficient and regiospecific catalytic cyclotrimerization of alkynes to form 1,2,4-substituted arenes has 17 been discovered. From a cheap and air-stable [Fe(salen)]2-µ-oxo complex and readily available pinacol borane (HBpin), a 18 monomeric [FeH(salen)]·Bpin species formed in situ acts as the active catalyst. This species is shown to feature a hemilabile 19 salen ligand stabilized via interactions with the boron entity. The formation, identity and reaction mechanism of the active 20 species is supported by complementary kinetic, spectroscopic and computational data. The active catalyst undergoes hydro- 21 metallation of a coordinated alkyne to form a vinyl iron species, stepwise additions of two more alkynes across the Fe-C bond 22 to form a pendant triene, which upon ring-closure forms the arene product. The catalytic cycle is closed by substitution of the 23 product with alkyne substrate. With the active [FeH(salen)]·Bpin catalyst, atom-efficient, intermolecular trimerization is 24 shown with high regioselectivity for a diverse range of substrate substitution patterns and presence of functional groups. 25 26 KEYWORDS iron, homogeneous catalysis, reaction mechanisms, density functional theory, salen ligands, cyclotrimerization 27 28 1. INRODUCTION Scheme 1. Previous cyclotrimerizations (1a-c), this 29 The cyclotrimerization of alkynes remains one of the most work (d) and structure of 1. 30 atom-efficient ways to prepare benzene rings.1,2 Since ben- 31 zene motifs are ubiquitous in organic chemistry,3 cyclotri- 32 merisation reactions have wide-ranging application poten- 4 5 33 tial including liquid crystals, light-emitting molecules, 6–9 10–12 34 natural products, and pharmaceuticals. The reaction of three molecules of acetylene to form benzene was first 35 discovered in the mid-19th century by Bertholet using high 36 temperatures and pressures.13 In 1948, Reppe et al. found a 37 practical catalytic route to trimerize propargyl alcohols at 38 much lower temperatures and ambient pressure.14 While 39 today a diverse range of catalytic procedures is available in 40 which polymeric and oligomeric side-products are mini- 41 mized,15,16 challenges remain: many of the catalysts used in 42 these syntheses require scarce and expensive platinum 43 group metals or relatively harsh conditions and many are 44 not regioselective. 45 If a terminal alkyne is trimerized, it can form two distinct 46 regioisomers with 1,3,5- or 1,2,4-substitution patterns. Of- 47 ten, the only way of controlling this is to use steric factors or cleverly tethered di-alkyne substrates to allow the pref- 48 erential formation of one isomer, as exemplified by Deiters‘ 49 ruthenium catalyst (Scheme 1a).8 While effective, this ap- 50 proach perhaps moderates the appealing atom efficiency of 51 the transformation, even if using earth-abundant cata- 52 lysts.17–19 53 54 55 56 57 58 59 60 ACS Paragon Plus Environment ACS Catalysis Page 2 of 27 Transition metal complexes featuring the salen (salen = a reducing agent, but also in forming the catalytically active 1 N,N’-bis(salicylidene)ethane-1,2-diamine) ligand are excel- complex itself. This second role provides a unique example 2 lent catalysts for a range of transformations, one notable ex- of salen hemilability via one of the phenoxy arms, resulting 3 ample being enantioselective epoxidations mediated by Ja- in the formation of an active [Fe(II)H(salen)]·Bpin species 4 cobsen’s catalyst.20 Our past work with iron(salen) com- (5). In the catalytically active complex, the iron center is li- 5 plexes explored hydrophosphination chemistry using an gated by an unprecedented twisted salen coordination en- 6 [Fe(salen)]2-µ-oxo pre-catalyst in which the iron ions have vironment. Our findings are supported by comprehensive 21 7 distorted square-pyramidal ligand spheres. During the experimental and computational investigations. 8 course of these studies it became apparent that the penta- coordinate iron center would need an activation event in or- 9 2. RESULTS AND DISCUSSION der to develop catalysis beyond hydrophosphination. Nota- 10 bly, studies by Hilt have shown that simple Fe(salen) com- 2.1 Optimization and Substrate Scope 11 plexes can be reduced by Zn to allow for epoxide ring ex- Preliminary reactions in MeCN (Table 1, entry 1) show 12 pansion (and thus C-C bond formation).22 With this in mind quantitative conversion of phenylacetylene (2a) to a mix- 13 we sought to expand the reactivity of the [Fe(salen)]2-µ-oxo ture of 1,3,5- and 1,2,4-triphenylbenzene (3a, 2:98 respec- 14 pre-catalyst to effect the cyclotrimerization of alkynes to tively) after 2 h with 1 eq. of HBpin and 5 mol% of 1. Reduc- 15 form (poly)cyclic molecules under mild conditions. ing the catalyst loading to 1 mol% and the reaction time to 16 Advances in the field of iron catalyzed cyclotrimerization 1 h gives the same conversion (entry 2). Solubility of 1 limits 17 have brought regioselective processes that have mitigated the solvent choice; Et2O and solvent-free conditions give 18 the requirement for expensive reagents. An example is the poor conversion and low isolated yield due to a protracted 19 highly active Fe(hmds)2 catalyzed trimerization system for- work-up procedure being necessary (compare entry 2 to 20 mulated by Jacobi von Wangelin and co-workers (Scheme entries 3 and 4). To elucidate the role of HBpin, a wide vari- 21 1b),23 which proceeds via a substrate-induced reduction of ety of reducing agents were tested (entries 5 to 15). None 22 the pre-catalyst to generate catalytically active nanopartic- achieve any conversion to the cyclotrimer, showing clearly that the speciation of the borane is important for reactivity. 23 ulate iron. During the preparation of this manuscript, Jacobi Similarly, the [Fe(salen)]2-µ-oxo pre-catalyst is essential 24 von Wangelin reported dual organo-photoredox/FeCl2-me- diated catalysis which is also nanoparticulate in nature.24 since reactions testing simple iron salts FeCl2 and FeCl3 in- 25 stead of 1 show no activity (SI, Section 3).