Ibrahim Sultan Mashima Laboratory Osaka University 2019/07/24 4,4’-Bipyridyl-catalyzed Reduction of Nitroarenes by Bis(neopentylglycolato)diboron Ibrahim Sultan Mashima Laboratory Osaka University 2019/07/24

Contents…. Introduction Previous Work Background Reaction Optimization Catalyst Screening Substrate Synthesis Substrate Scope Mechanistic Study Imine Synthesis Future Work

Introduction 4 Million Ton Aniline production/year Global Synthetic and Bio-based Aniline Market in 2017, by Application Market Research Future (https://www.marketresearchfuture.com/reports/synthetic-bio-based-aniline- market-5981) Methyl di-phenylene isocyanate (MDI)-primarily used in rigid polyurethane (PU) foams.

Previous Work Beller et. Al., Chem. Rev. 2019, 119, 2611 Chemoselectivity, Special high pressure equipment, Inflammable hydrogen gas, Hazardous reagents, Relatively expensive metal complexes. Beller et. Al., Chem. Rev. 2019, 119, 2611 Corma et. Al., Science 2006,313, 332.

Catalyst “catalysis” term was first introduced by Jons Jacob Berzelius in 1835 “A catalyst is a substance which affects the rate of a chemical reaction without being part of its end products” “catalyst” was firstly Defined by Wilhelm Ostwald in 1900 5 Ertl, G. Reactions at surfaces: from atoms to complexity (Nobel Lecture).  Angew. Chem. Int. Ed.  2008 47, 3524–3535

Background Mashima et. al., Chem. Eur. J. 2018, 24, 11278. Suginome et al., Am. Chem. Soc. 2015, 137, 2852

Reaction Optimization (a) The reactions carried out in the J-young NMR tubes. (b)The yield was calculated by GC analysis using the dodecane as an internal reagent. (c)7.2 μL of H2O was added. (d)Degasification by Sonification was carried out for 3 minutes upon mixing all reagents and 1 h later after putting in oil bath, mixture was gently shaken. Entry 1a (mmole) B2Nep2 (equiv.) Bipyridyl (mol %) CH3CN (mL) Time (hr) 2a ( %)(b) Conv (%)(b) 1 0.1 3.3 2,2'-bipy 5 mol% 0.5 24 14 20 2 4,4'-bipy 5 mol% 78 81 3 3.6 86 >99 4 0.4 1.5 18 94 97 5 6 84 6(c) 0.75 82 75 7 4,4'-bipy 0.5 mol% 63 8 4,4'-bipy 0.25mol% 64 9(d) 4,4'-bipy 2 mol% 93 99

Reductant-Boron Screening Entry reductant Conv. (%)b 2a (%)b 1 B2nep2 >99 93 7d 89 2c 91 85 8e 49 39 3 B2hex2 9f 4 n.d. B2pin2 2 10 HBpin 8 6 5 B2cat2 83 11 H3B·NMe3 B2(OH)4 99 86 12 Me2PhSiBpin a Conditions: nitrobenzene (0.40 mmol), boron compound (1.44 mmol), 4,4-bipyridine (2 mol%, relative to nitrobenzene), CH3CN (1.5 mL), 100 °C, 6 h, under air in J-young NMR tube. b Determined by GC using dodecane as internal standard. c Reaction under Ar. d 1 mol% of 4,4’-bipyridyl. e Reaction at room temperature for 24 h. f No 4,4bipyridyl’-.

Catalyst Screening Entry Catalyst 2a ( %)(b) Conv (%) 1 2,2'-bipirdyl (a)Conditions: In J-young tube nitrobenzene (0.4mmol), B2Nep2(1.4mmol), catalyst loading relative to the 1a (2mol%), CH3CN (1.5mL), 1000C, 6hr. Under air. (b) Determined by GC analysis and using the dodecane as an internal standard. Entry Catalyst 2a ( %)(b) Conv (%) 1 2,2'-bipirdyl 2 9 3,3-bipyridyl 3 6 1,10-phenanthroline 42 52 4 Pyrazine 8 14 5 2,3-dimethylpyrazine 2,5-dimethylpyrazine 15 21 7 2,6-dimethylpyrazine 43 59 2,3,5,6-tetramethylpyrazine

Catalyst Screening Li at el.Angew.Chem. Int .Ed. 2016 , 55 ,5 985 Entry Catalyst 2a ( %)(b) Conv (%) 9 Quinoxaline 11 21 10 Phenazine 2 5 Pyridine 13 12 2,6-dimethypyridine 4-phenylpyridine 4 18 14 4-Cyanopyradine 17 24 15 Quinoline 16 Isoquinoline Li at el.Angew.Chem. Int .Ed. 2016 , 55 ,5 985

Substrate Synthesis Org. Lett. 2008, 10 (19), 4383-4386   Org. Lett. 2012, 14 (7), 1736-1739 J. Heterocyclic Chem. 2018, 55, 1917

Substrate Scope 12

Substrate Scope

Substrate Scope

Substrate Scope 15

Substrate Scope 16 16

Mechanistic Study 17 17 17 17

Mechanistic Study 18 18 18 18 18

Mechanistic Study 19 19 19 19 19 19

Proposed Mechanism 20 20 20

Application-Ketimine Synthesis 1 2 equiv of acetophenone was used 21 21 21 21

Imine Synthesis

Continue… In the absence of carbonyl compound the main product observed by 1H NMR is: Future Work Scope for aldimine formation from the reduction of azoarenes in the presence of aldehyde.

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