Employing Water as the Hydride Source in Synthesis: A Case Study of

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Employing Water as the Hydride Source in Synthesis: A Case Study of Diboron Mediated Alkyne Hydroarylation Santhosh Rao, M. Nibin Joy, and Kandikere Ramaiah Prabhu J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01965 • Publication Date (Web): 15 Oct 2018 Downloaded from http://pubs.acs.org on October 16, 2018

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The Journal of Organic Chemistry

Employing Water as the Hydride Source in Synthesis: A Case Study of Diboron Mediated Alkyne Hydroarylation Santhosh Rao, M. Nibin Joy and Kandikere Ramaiah Prabhu* Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, Karnataka, India.

ABSTRACT: We present an approach to utilize water as the hydride source via Pd(II)/Pd(0) catalysis. As a case study, we have achieved a diboron mediated Pd(II)-catalyzed hydroarylation of alkynes using arylboronic acids. This approach not only complements conventional reactivity of Pd via Pd(0)/Pd(II) cycle for the hydroarylation, but also utilizes water as the hydride source. We believe, this would particularly be beneficial in utilizing water as a reagent.

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INTROUDCTION Diboron compounds have proved to be an efficient mediator of various transformations by undergoing B-B bond cleavage.1,2 The characteristic high oxophilicity of the boron center can facilitate energetically demanding transformations. With this understanding, we have successfully carried out a homogeneous palladium catalyzed hydride transfer from water to reduce alkenes and alkynes.3,4 In this direction, we identified H-Pd-OAc as the crucial catalytic intermediate and was employed to construct C-H bonds (hydrogenation) in a stereodivergent fashion.4 Recognizing the catalytic species’ importance in generating hydrometallated species, we undertook an investigation to explore its application in the C-C bond formation (Scheme 1).5,6 Scheme 1. Utilizing Water as the Hydride Source

Oxidative addition to Pd(0) is one of the most studied modes of reactivity in the organopalladium chemistry.7 Since the discovery of the Suzuki-Miyaura coupling, arylboron reagents have been extensively used for cross-coupling reactions using Pd(0) catalysts.7-9 In this direction, alkyne hydroarylation 2 ACS Paragon Plus Environment

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was achieved independently by Hayashi and Shirakawa in 2001 using Rh- and Ni-catalysts respectively.10,11 Oh reported the first example of Pd(0)-catalyzed alkyne hydroarylation using arylboronic acids12 in the presence of acetic acid. Subsequently, other variations of organoboronic acid addition reactions to alkynes have also been explored.13-21 In all these cases, an occurrence of Pd(0)/Pd(II) catalysis was essential. In continuation of our study of diboron reagents,22,23 we hypothesized an alkyne hydroarylation with organoboronic acids. The mechanistic underpinning of the reactivity of the Pd-catalyst in the B2pin2H2O system served as the basis for the development for the new reaction. Our approach consisted of probing the reactivity of Pd species with organoboronic acids via Pd(II)/Pd(0) cycle. Herein, we present a new means to generate reactive alkenylpalladium intermediates comprising hydrogen derived from water via Pd(II)/Pd(0) catalysis.24,25 As a proof of the concept, we also attempted to explore the scope of different substrates.

RESULTS AND DISCUSSION We undertook the optimization studies with diphenylacetylene (1a) and 4-acetylphenylboronic acid (2w) as model substrates, Pd(OAc)2 as the catalyst, PCy3 as the ligand, B2pin2 as a sacrificial transfer hydrogenating reagent, and H2O as an hydride source. We were pleased to see the product formation in the initial set of controls as the reaction in toluene furnished the desired product 3aw in 42% yield along with the corresponding hydroborylated product 4a in 40% (entry 1). Additional solvent screening controls (entries 2-6, see SI, Table S-1 for additional details) indicated THF as the most suitable solvent to obtain 3aw exclusively (87% yield) and only a trace amount of 4a was observed (entry 6).

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Table 1. Reaction Optimizationa

entry 1

B2pin2/ H2O 1.1/5

2w (equiv) 1.1

solvent/t (°C) toluene/100

3aw%b (42)

4a%b (40)

2

1.1/5

1.1

DME/80

51

22

3

1.1/5

1.1

DME-H2O/80

14

65

4

1.0/2.5

1.1

DME/80

51

22

5

1.0/2.5

1.0

DME/80

70

trace

6c

1.0/2

1.0

THF/80

>95(87)

95% (87%) H

Ph

3am 95% (89%) Cl

H

H

Ph

H

Ph

3al >95% (88%)

3ak 68% (65%)

OMe

Ph

Ph

e

Ph

F

Ph

CN

Ph Ph

3aic 90% (84%)

H

CN

H

Ph OEt

3ahc 85% (75%) OCF3

H

H

Ph

3ag 75% (70%)

Ph 3aec (80%)

3ad 90% (81%)

Ph

Ph

Ph 3af 85% (77%)

Ph d

H

OMe

H Ph

3ac 90% (85%) OMe

H

Me

c

3ab >95% (93%)

iPr

Ph

Ph

3aa >95% (90%)

Ph 3 NMR yieldb (isolated yield)

H

Ph

c

R2

Ph

H

Ph Ph

H

Ph

CF3 Ph

3asf >95% (97%)

3at >95% (92%)

HO CHO

H

COMe

H

CO2Me

H

H Ph Ph Ph 3au 74% (70%)

Ph Ph

3av 87% (76%)

Ph Ph

3aw >95% (87%)

Ph

3ax 70% (60%)

Reaction conditions: 1a (0.5 mmol), 2 (0.5 mmol), THF (2 mL), 4h. b 1H NMR yield is measured using terephthalaldehyde as the internal standard. Numbers in parentheses are isolated yields. c 1h. d 2h. e 12 h. f 30 min.



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Additionally, the scope of the alkynes was also studied (1b-1f) (Scheme 4). To begin with, a heterocyclic system (1b) was tried and we were pleased to see an excellent yield of the product (3ba, 85%). On the other hand, a terminal alkyne such as phenylacetylene (1c) provided the desired product as one regioisomer (3ca, 65%). This indicated a preferential addition of phenylboronic acid derived phenyl group on to the activated alpha-carbon. When other unsymmetrical internal alkynes (1d-1f) were used, the regioselectivity was poor due to insufficient electronic control by the alkyne substrate necessary for the regioselectivity. However, the results did show a promise that the method can be stabilized to obtain one unconventional regioisomer (such as 3ea and 3fa, wherein conventional methods lead to alphafunctionalized products).6,13 We are at present pursuing the possibility of obtaining exclusive formation of the unconventional regioisomer in the unsymmetrical alkynes. Further, when sterically differentiated alkyne viz. trimethyl(phenylethynyl)silane was tested, it underwent a facile hydroarylation to provide predominantly single regioisomer (3ga, 77%, regiomeric ratio α:β=97:3) with trace (95% conversion

3aw (42%)

Ph

B(OH)2

1a 0.5 mmol

2w 0.5 mmol

B2pin2 (0.5 mmol) H2O (1 mmol) THF, 80 oC, 4h 90% conversion

Ph

1a 0.5 mmol

B(OH)2 2w 0.5 mmol

H2O (1 mmol) THF, 80 oC, 4h 70% conversion

Ph

3aw NMR yield = 69% Isolated yield = (62%)

4a 26%

Ac

H

H Bpin

Ph

Ph

Ph

Ph

3aw 83%

Pd(PCy3)2 (1 mol %) AcOH (2 mol %)

+

Bpin

Ph

Ac Ph

H Ph

Ph


+

4a trace

Ac

H

Ac Ph

Ph

Ph


+

Bpin

Ph

Ph

Ac Ph

H

4a trace

Ac

H

H Bpin

Ph

Ph

Ph

Ph

3aw 66%

B) Probing Palladium's C-B Oxidative Addition Capability Ac Ac Ac Pd(OAc)2 (1 mol %) PCy3 (2 mol %) B2pin2 (0.5 mmol) H2O (1 mmol) B Ac HO OH THF, 80 oC, 4h 2w 2ww >95% conversion 0.5 mmol nd

4a trace

B O

O

2w' 76%



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Pd(0)-catalysts are known to oxidatively insert between C-B bond.7 Hence, in order to uncover the reactivity of Pd in our system, we performed a control experiment under standard conditions but with 1a omitted. Here, the formation of homocoupled biaryl product (2ww) from 2w would suggest the oxidative addition of C-B bond to Pd(0) is possible in the present system.7b However, we did not observe 2ww in the reaction mixture, instead only the corresponding transesterified boronate ester (2w’) was observed in 76% yield. This control ruled out the possibility of oxidative addition in the reaction. This also suggested that the arylboronic acid may be converted to corresponding arylbornate ester before undergoing the transmetallation with Pd(II). Hence, considering our experimental observations and the literature precedence,6,7,28 we propose a plausible mechanism (Scheme 6). The first step is the coordination of the ligands to the Pd(OAc)2 center to obtain Pd(II)(PCy3)2(OAc)2. Pd(PCy3)2 is here afterwards represented as [Pd] for simplicity. [Pd](OAc)2 species can now undergo transmetallation with B2pin2 to generate pinB-[Pd]-OAc species with the elimination of AcO-Bpin. In the presence of water, pinB-[Pd]-OAc can undergo σ-bond metathesis to furnish H-[Pd]-OAc catalytic species. Above mentioned steps constitute an efficient transfer of a hydride from water to the metal-center. Now H-[Pd]-OAc can undergo hydropalladation with an alkyne (1) followed by transmetallation with organoboronic acids (2, R1B(OR2)2). A reductive elimination of this hydropalladated intermediate can now lead to the hydroarylated product (3). Oxidative addition of AcOH generated during the reaction can now undergo oxidative addition to [Pd](0) species,[12,28] which leads to the active Pd(II) species for the continuation of the catalytic cycle.


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Scheme 6. Plausible Mechanism

CONCLUSION In summary, we have utilized water as a hydride source via Pd(II)/Pd(0) catalysis. As a proof of concept, we have developed a simple yet effective hydroarylation method to obtain functionalized olefins. The method, accomplished under externally added acid-free conditions, would particularly be useful in the late stage functionalization of natural products/biomolecules. To conclude, we believe our approach of utilizing water for molecular construction holds promise from a mechanistic standpoint.

EXPERIMENTAL SECTION General Information: All chemicals were purchased from commercial suppliers and used as delivered. Pd(OAc)2 (product number: 10516) has been obtained from Alfa Aesar. Tricyclohexylphosphine (product number: 261971) was procured from Sigma Aldrich. THF (Finar AR dry grade) was used directly for all the procedures. 1H NMR and 13C NMR spectra were recorded at 400 MHz and 100 MHz, 15 ACS Paragon Plus Environment


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respectively. Chemical shifts are reported in parts per million (ppm) and coupling constants in Hertz (Hz). Tetramethylsilane (TMS) (δ = 0.00 ppm) or residual CHCl3 in CDCl3 (δ = 7.26 ppm) served as internal standard for recording. 1H NMR and the residual non-deuterated solvent signal of CDCl3 (δ = 77.16 ppm) was used as internal standard for 13C NMR (proton decoupled).1,2 IR spectra were recorded using Perkin Elmer FT-IR instrument; Mass spectra (EI) were recorded using Shimadzu; and Highresolution mass spectra (HRMS) were recorded on Q-TOF (Micromass) spectrometer. Melting points of the product were determined on Buchi melting point apparatus. Flash column chromatography was carried out using commercially obtained silica gel and thin-layer chromatography (TLC) was performed using Merck silica gel 60 F254 TLC plates. General Experimental Procedure for the Hydroarylation of Alkynes Using Arylboronic Acids: To a pre-dried 10 mL screw cap equipped reaction vial, water (1 mmol, 18 mg), alkyne (1, 0.5 mmol), B2Pin2 (0.5 mmol, 127 mg), arylboronic acid (2, 0.5 mmol), PCy3 (2 mol %, 2.8 mg) and Pd(OAc)2 (1 mol %, 1.1 mg) were added, dissolved in dry THF (2 mL) and the reaction mixture was heated at 80 °C in a pre-heated metal block for 30 min to 12h with continuous stirring. After the completion of the reaction, the reaction mixture was filtered using a short column using diethyl ether. The filtrate was distilled under reduced pressure and the crude mixture was dissolved in sufficient amount of CDCl3. To this, 0.125 mmol terephthalaldehyde as the internal standard was added, dissolved and submitted for NMR analysis. The crude mixture was then purified by column chromatography to afford the hydroarylated yield. Characterization Data for Products. 3aa: Ethene-1,1,2-triyltribenzene.15 General procedure was followed for 1h; yellow oily liquid; yield 90% (115 mg); Rf (petroleum ether) 0.9; IR (neat, cm-1) νmax 3023, 1492; 1H NMR (CDCl3, 400 MHz) δ 7.33 – 7.25 (m, 8H), 7.21 – 7.18 (m, 2H), 7.13 – 7.06 (m, 3H), 7.05 – 7.01 (m, 2H), 6.96 (s, 1H);


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C{1H} NMR (CDCl3, 100 MHz) δ 143.5, 142.7, 140.5, 137.5, 130.5, 129.7, 128.8, 128.3, 128.3,

128.1, 127.7, 127.6, 127.5, 126.9. 3ab: (E)-(1-(p-Tolyl)ethene-1,2-diyl)dibenzene.15 General procedure was followed for 1h; white solid; yield 93% (126 mg); Rf (petroleum ether) 0.8; mp 76 – 78 °C; IR (neat, cm-1) νmax 1509; 1H NMR (CDCl3, 400 MHz) δ 7.32 – 7.29 (m, 3H), 7.22 – 7.18 (m, 4H), 7.13 – 7.07 (m, 5H), 7.02 – 7.00 (m, 2H), 6.93 (s, 1H), 2.34 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 142.6, 140.7, 140.6, 137.6, 137.5, 130.5, 129.6, 129.1, 128.7, 128.1, 127.6, 127.5, 126.7, 21.1. 3ac: (E)-(1-(o-Tolyl)ethene-1,2-diyl)dibenzene.15 General procedure was followed for 1h; yellow liquid; yield 85% (115 mg); Rf (petroleum ether) 0.8; IR (neat, cm-1) νmax 2362, 1446; 1H NMR (CDCl3, 400 MHz) δ 7.29 – 7.27 (m, 1H), 7.22 – 7.19 (m, 5H), 7.17 – 7.12 (m, 8H), 6.61 (s, 1H), 2.11 (s, 3H); 13

C{1H} NMR (CDCl3, 100 MHz) δ 144.1, 143.1, 140.4, 137.5, 136.4, 130.6, 130.3, 130.2, 130.0,

129.6, 128.3, 128.1, 127.6, 127.2, 126.9, 125.8, 20.7. 3ad: (E)-(1-(4-Isopropylphenyl)ethene-1,2-diyl)dibenzene.15 General procedure was followed for 2h; colorless liquid; yield 81% (121 mg); Rf (petroleum ether) 0.8; IR (neat, cm-1) νmax 3022, 2960, 1505; 1

H NMR (CDCl3, 400 MHz) δ 7.33 – 7.29 (m, 3H), 7.25 (d, J = 8 Hz, 2H), 7.21 – 7.19 (m, 2H), 7.16 (d,

J = 8 Hz, 2H), 7.12 – 7.06 (m, 3H), 7.00 (d, J = 6.8 Hz, 2H), 6.95 (s, 1H), 2.89 (m, J = 6.8 Hz, 1H), 1.25 (d, J = 7.2 Hz, 6H); 13C{1H} NMR (CDCl3, 100 MHz) δ 148.5, 142.6, 141.0, 140.6, 137.6, 130.5, 129.6, 128.7, 128.1, 127.61, 127.56, 127.45, 126.7, 126.4, 33.9, 24.1. HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C23H22Na 321.1619; Found 321.1617. 3ae: (E)-1-(1,2-Diphenylvinyl)naphthalene.14 General procedure was followed for 1h; orange liquid; yield 80% (123 mg); Rf (petroleum ether) 0.7; IR (neat, cm-1) νmax 3053, 1494; 1H NMR (CDCl3, 400 MHz) δ 8.10 (d, J = 8.4 Hz, 1H), 7.83 – 7.78 (m, 2H), 7.45 – 7.18 (m, 15H), 6.79 (s, 1H);

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C{1H}



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NMR (CDCl3, 100 MHz) δ 142.3, 141.5, 141.1, 137.5, 134.1, 132.0, 131.7, 129.9, 129.6, 128.5, 128.4, 128.2, 128.0, 127.5, 127.4, 127.1, 126.3, 126.1, 125.8, 125.4. 3af: (E)-(1-(4-Ethoxyphenyl)ethene-1,2-diyl)dibenzene. General procedure was followed; yellow solid; yield 77% (116 mg); Rf (10% EtOAc – petroleum ether) 0.9; mp 93 – 95 °C; IR (neat, cm-1) νmax 3446, 2979, 1508; 1H NMR (CDCl3, 400 MHz) δ 7.32 – 7.27 (m, 3H), 7.23 – 7.17 (m, 4H), 7.09 – 7.03 (m, 3H), 6.98 (d, J = 7.2 Hz, 2H), 6.87 (s, 1H), 6.81 – 6.79 (m, 2H), 3.97 (q, J = 7.2 Hz, 2H), 1.37 (t, J = 6.8 Hz, 3H);

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C{1H} NMR (CDCl3, 100 MHz) δ 158.7, 142.2, 140.7 137.7, 135.9, 131.7, 130.5, 129.5,

128.8, 128.7, 128.0, 127.4, 126.5, 114.2, 63.5, 14.9; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H20OH 301.1592; Found 301.1591. 3ag: (E)-(1-(3,4-Dimethoxyphenyl)ethene-1,2-diyl)dibenzene. General procedure was followed; white solid; yield 70% (111 mg); Rf (10% EtOAc – petroleum ether) 0.5; mp 120 – 122 °C; IR (neat, cm-1) νmax 3434, 2362, 1512; 1H NMR (CDCl3, 400 MHz) δ 7.34 – 7.31 (m, 3H), 7.22 – 7.20 (m, 2H), 7.13 – 7.06 (m, 3H), 7.01 (d, J = 6.8 Hz, 2H), 6.90 (s, 2H), 6.84 – 6.78 (m, 2H), 3.88 (s, 3H), 3.82 (s, 3H); 13

C{1H} NMR (CDCl3, 100 MHz) δ 148.9, 148.8, 142.5, 140.5, 137.6, 136.6, 130.6, 129.6, 128.7,

128.1, 127.5, 126.9, 126.7, 120.7, 110.9, 56.1, 56.0; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C22H21O2H 317.1542; Found 317.1538. 3ah: (E)-(1-(2-Ethoxyphenyl)ethene-1,2-diyl)dibenzene. General procedure was followed for 1h; yellow liquid; yield 75% (113 mg); Rf (10% EtOAc – petroleum ether) 0.8; IR (neat, cm-1) νmax 3398, 1445; 1H NMR (CDCl3, 400 MHz) δ 7.33 (dd , J = 7.2 Hz, J = 1.6 Hz, 1H), 7.26 – 7.21 (m, 1H), 7.19 – 7.16 (m, 5H), 7.14 – 7.06 (m, 5H), 6.96 – 6.91 (m, 1H), 6.80 (d, J = 8 Hz, 1H), 6.77 (s, 1H), 3.74 (q, J = 7.2 Hz, 2H), 0.95 (t, J = 7.2 Hz, 3H);

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C{1H} NMR (CDCl3, 100 MHz) δ 156.8, 141.3, 141.3, 137.7, 133.8,

131.2, 129.9, 129.7, 129.7, 129.0, 127.96, 127.94, 126.8, 126.7, 120.6, 112.7, 64.0, 14.5. HRMS (ESITOF) m/z: [M + H]+ Calcd for C22H20OH 301.1592; Found 301.1591. 18 ACS Paragon Plus Environment

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3ai: (E)-(1-(2-Methoxyphenyl)ethene-1,2-diyl)dibenzene. General procedure was followed for 1h; light yellow solid; yield: 84% (120 mg); Rf (10% EtOAc – petroleum ether) 0.7; mp 79 – 81 °C; IR (neat, cm1

) νmax 3022, 1250; 1H NMR (CDCl3, 400 MHz) δ 7.29 – 7.24 (m, 2H), 7.21 – 7.17 (m, 5H), 7.13 – 7.05

(m, 5H), 6.96 – 6.92 (m, 1H), 6.86 (d, J = 8.4 Hz, 1H), 6.79 (s, 1H), 3.58 (s, 3H);

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C{1H} NMR

(CDCl3, 100 MHz) δ 157.4, 141.2, 140.5, 137.6, 133.8, 131.2, 130.3, 129.7, 129.6, 128.9, 128.1, 128.0, 126.9, 126.7, 120.7, 111.9, 55.8; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H18ONa 309.1255; Found 309.1252. 3aj: (E)-4-(1,2-Diphenylvinyl)benzonitrile. General procedure was followed for 1h; white solid; yield 87% (122 mg); Rf (10% EtOAc – petroleum ether) 0.6; mp 117 – 119 °C; IR (neat, cm-1) νmax 2924, 2361, 1598; 1H NMR (CDCl3, 400 MHz) δ 7.58 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.36 – 7.35 (m, 3H), 7.18 – 7.13 (m, 5H), 7.05 – 7.02 (m, 3H);

13

C{1H} NMR (CDCl3, 100 MHz) δ 147.9,

141.0, 139.3, 136.6, 132.1, 131.0, 130.3, 129.8, 129.1, 128.2, 128.1, 128.1, 127.7, 119.1, 110.8; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H15NNa 304.1102; Found 304.1103. 3ak: (E)-2-(1,2-Diphenylvinyl)benzonitrile. General procedure was followed for 12h; white solid; yield 65% (74 mg); Rf (10% EtOAc – petroleum ether) 0.5; mp 76 – 78 °C; IR (neat, cm-1) νmax 3057, 2362; 1

H NMR (CDCl3, 400 MHz) δ 7.69 (dd, J = 7.6 Hz, J = 0.8 Hz, 1H), 7.38 – 7.33 (m, 1H), 7.30 – 7.28

(m, 4H), 7.20 – 7.11 (m, 7H), 6.92 (s, 1H);

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C{1H} NMR (CDCl3, 100 MHz) δ 147.9, 139.3, 139.3,

136.4, 133.8, 133.3, 132.4, 130.5, 130.4, 129.8, 128.7, 128.2, 128.0, 127.7, 127.7, 118.5, 111.8; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H15NNa 304.1102; Found 304.1100. 3al: (E)-(1-(4-(Trifluoromethoxy)phenyl)ethene-1,2-diyl)dibenzene.15 General procedure was followed; yellow liquid; Isolated yield 88% (150 mg); Rf (5% EtOAc – petroleum ether) 0.8; IR νmax (neat, cm-1) 3056, 2362, 1260; 1H NMR (CDCl3, 400 MHz) δ 7.34 – 7.32 (m, 5H), 7.21 – 7.17 (m, 2H), 7.15 – 7.10 19 ACS Paragon Plus Environment


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(m, 5H), 7.03 – 7.01 (m, 2H), 6.94 (s, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 148.7 (d, J = 1.8 Hz), 142.3, 141.4, 140.1, 137.2, 132.1, 130.5, 129.7, 129.0, 128.9, 128.2, 127.8, 127.2, 120.8, 120.7 (q, J = 255.5 Hz). 3am: (E)-(1-(4-Fluorophenyl)ethene-1,2-diyl)dibenzene.15 General procedure was followed; white solid; yield 89% (122 mg); mp 67 – 69 °C; Rf (5% EtOAc – petroleum ether) 0.9; IR (neat, cm-1) νmax 3054, 1504; 1H NMR (CDCl3, 400 MHz) δ 7.33 – 7.26 (m, 5H), 7.19 – 7.17 (m, 2H), 7.15 – 7.09 (m, 3H), 7.02 – 6.97 (m, 4H), 6.89 (s, 1H);

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C{1H} NMR (CDCl3, 100 MHz) δ 162.5 (d, J = 245.6 Hz),

141.7, 140.3, 139.7 (d, J = 3.2 Hz), 137.4, 130.5, 129.7, 129.3 (d, J = 8 Hz), 128.8, 128.1, 127.7, 126.9, 115.2 (d, J = 21.3 Hz). 3an: (E)-(1-(2-Fluorophenyl)ethene-1,2-diyl)dibenzene.32a General procedure was followed for 1h; yellow liquid; yield 81% (111 mg); Rf (5% EtOAc – petroleum ether) 0.9; IR (neat, cm-1) νmax 3024, 1488; 1

H NMR (CDCl3, 400 MHz) δ 7.26 – 7.18 (m, 7H), 7.13 – 7.00 (m, 7H), 6.88 (s, 1H);

13

C{1H} NMR

(CDCl3, 100 MHz) δ 160.5 (d, J = 247.4, Hz), 140.3, 137.2 (d, J = 17.1 Hz), 131.8 (d, J = 3.8 Hz), 131.4 (d, J = 3.2 Hz), 129.9, 129.7, 129.1 (d, J = 8.3 Hz), 128.6, 128.1, 127.5, 127.1, 124.0 (d, J = 3.6 Hz), 116.1 (d, J = 22.5 Hz). 3ao: (E)-(1-(3-Fluorophenyl)ethene-1,2-diyl)dibenzene.32b General procedure was followed for 1h; white solid; yield 93% (127 mg); mp 76 – 78 °C; Rf (5% EtOAc – petroleum ether) 0.9; IR (neat, cm-1) νmax 3024, 1579; 1H NMR (CDCl3, 400 MHz) δ 7.34 – 7.30 (m, 3H), 7.25 – 7.21 (m, 1H), 7.20 – 7.17 (m, 2H), 7.14 – 7.09 (m, 4H), 7.02 – 6.99 (m, 3H), 6.97 – 6.93 (m, 2H);

13

C{1H} NMR (CDCl3, 100

MHz) δ 163.0 (d, J = 243.7 Hz), 145.9 (d, J = 7.3 Hz), 141.6 (d, J = 2.1 Hz), 140.0, 137.1, 130.4, 129.8, 129.7 (d, J = 8.3 Hz), 129.2, 128.9, 128.1, 127.8, 127.2, 123.3 (d, J = 2.5 Hz), 114.5 (d, J = 22.0 Hz), 114.4 (d, J = 21.2 Hz).


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3ap: (E)-(1-(3,5-Difluorophenyl)ethene-1,2-diyl)dibenzene.15 General procedure was followed for 1h; light yellow solid; yield 92% (135 mg); mp 69 – 71 °C; Rf (5% EtOAc – petroleum ether) 0.9; IR (neat, cm-1) νmax 3400, 2361, 1618; 1H NMR (CDCl3, 400 MHz) δ 7.34 – 7.33 (m, 3H), 7.18 – 7.11 (m, 5H), 7.02 – 6.99 (m, 2H), 6.98 (s, 1H), 6.84 – 6.82 (m, 2H), 6.73 – 6.67 (m, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 163.0 (dd, J = 246.1, 13.1 Hz), 146.9 (t, J = 9 Hz), 140.6 (t, J = 2.3 Hz), 139.3, 136.7, 130.4, 130.0, 129.9, 129.1, 128.2, 128.0, 127.5, 110.4 (dd¸ J = 18.6, 6.8 Hz), 102.8 (t, J = 25.5 Hz). 3aq: (E)-(1-(4-Chlorophenyl)ethene-1,2-diyl)dibenzene.15 General procedure was followed; yellow liquid; yield 80% (116 mg); Rf (petroleum ether) 0.8; IR (neat, cm-1) νmax 3445, 1644; 1H NMR (CDCl3, 400 MHz) δ 7.32 – 7.30 (m, 3H), 7.24 – 7.21 (m, 4H), 7.20 – 7.13 (m, 2H), 7.12 – 7.09 (m, 3H), 7.02 – 7.00 (m, 2H), 6.92 (s, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 142.02, 141.52, 140.01, 137.17, 133.45, 130.43, 129.67, 128.98, 128.88, 128.61, 128.47, 128.13, 127.75, 127.08. 3ar: (E)-(1-(4-(Trifluoromethyl)phenyl)ethene-1,2-diyl)dibenzene.15 General procedure was followed for 30 min; yellow liquid; yield 87% (141 mg); Rf (petroleum ether) 0.8; IR (neat, cm-1) νmax 3057, 1324; 1H NMR (CDCl3, 400 MHz) δ 7.54 (d, J = 8 Hz, 2H), 7.41 (d, J = 8 Hz, 2H), 7.34 – 7.31 (m, 3H), 7.21 – 7.12 (m, 5H), 7.05 – 7.02 (m, 2H), 7.01 (s, 1H);

13

C{1H} NMR (CDCl3, 100 MHz) δ 147.1,

141.5, 139.8, 136.9, 131.1, 130.4, 130.2, 129.8, 129.0, 128.2, 128.2 (q, J = 22.0 Hz), 127.9, 127.4, 125.3 (q, J = 3.6 Hz), 124.4 (q, J = 270.1 Hz). 3as: (E)-(1-(3-(Trifluoromethyl)phenyl)ethene-1,2-diyl)dibenzene.32c General procedure was followed for 30 min; white solid; yield 97% (157 mg); mp 72 – 74 °C; Rf (petroleum ether) 0.9; IR (neat, cm-1) νmax 3060, 1329; 1H NMR (CDCl3, 400 MHz) δ 7.62 (s, 1H), 7.52 (d, J = 7.2 Hz, 1H), 7.45 – 7.37 (m, 2H), 7.34 – 7.32 (m, 3H), 7.21 – 7.17 (m, 2H), 7.13 – 7.12 (m, 3H), 7.05 – 7.03 (m, 2H), 6.98 (s, 1H); 13

C{1H} NMR (CDCl3, 100 MHz) δ 144.4, 141.5, 139.7, 137.0, 131.1, 130.5, 130.9 (q, J = 31.9 Hz),



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129.81, 129.78, 129.0, 128.8, 128.2, 128.0, 127.4, 124.4 (q, J = 270.7 Hz), 124.3 (m, J = 3.9 Hz), 124.0 (q, J = 4.0 Hz) . 3at: (E)-(1-(4-Fluoro-3-(trifluoromethyl)phenyl)ethene-1,2-diyl)dibenzene.15 General procedure was followed; yellow liquid; yield 92% (157 mg); Rf (5% EtOAc – petroleum ether) 0.8; IR (neat, cm-1) νmax 1502, 1136; 1H NMR (CDCl3, 400 MHz) δ 7.59 (d, J = 6.8 Hz, 1H), 7.43 – 7.41 (m, 1H), 7.35 – 7.33 (m, 3H), 7.18 – 7.09 (m, 6H), 7.04 – 7.02 (m, 2H), 6.92 (s, 1H);

13

C{1H} NMR (CDCl3, 100 MHz) δ

159.2 (dq, J = 255.0, 2.0 Hz), 140.5, 140.1 (d, J = 3.9 Hz), 139.5, 136.9, 133.0 (d, J = 8.2 Hz), 130.4, 129.7, 129.6, 129.1, 128.2, 128.1, 127.4, 126.1 (q, J = 4.5 Hz), 122.3 (q, J = 270.6 Hz), 116.8 (d, J = 20.6 Hz). 3au: (E)-(3-(1,2-Diphenylvinyl)phenyl)methanol. General procedure was followed; yellow oily liquid; yield 70% (100 mg); Rf (10% EtOAc – petroleum ether) 0.1; IR (neat, cm-1) νmax 3332, 3021, 1026; 1H NMR (CDCl3, 400 MHz) δ 7.32 – 7.28 (m, 4H), 7.27 – 7.25 (m, 2H), 7.23 – 7.21 (m, 1H), 7.19 – 7.17 (m, 2H), 7.13 – 7.08 (m, 3H), 7.02 – 6.99 (m, 2H), 6.96 (s, 1H), 4.61 (s, 2H), 1.95 (s, 1H);

13

C{1H}

NMR (CDCl3, 100 MHz) δ 143.9, 142.5, 140.9, 140.3, 137.4, 130.4, 129.7, 128.8, 128.6, 128.1, 127.6, 127.1, 126.9, 126.3, 126.2, 65.3; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H18ONa 309.1255; Found 309.1252. 3av: (E)-4-(1,2-Diphenylvinyl)benzaldehyde. General procedure was followed; white solid; yield 76% (108 mg); mp 75 – 77 °C; Rf (10% EtOAc – petroleum ether) 0.6; IR (neat, cm-1) νmax 2362, 1696; 1H NMR (CDCl3, 400 MHz) δ 9.97 (s, 1H), 7.80 (d, J = 8 Hz, 2H), 7.46 (d, J = 8.4 Hz, 2H), 7.35 – 7.33 (m, 3H), 7.19 – 7.17 (m, 2H), 7.14 – 7.12 (m, 3H), 7.08 (s, 1H), 7.04 – 7.02 (m, 2H);

13

C{1H} NMR

(CDCl3, 100 MHz) δ 191.8, 149.5, 141.5, 139.6, 136.7, 135.3, 130.8, 130.3, 129.8, 129.8, 129.0, 128.2, 128.1, 127.9, 127.5; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C21H16ONa 307.1099; Found 307.1089. 22 ACS Paragon Plus Environment

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3aw: (E)-1-(4-(1,2-Diphenylvinyl)phenyl)ethan-1-one. General procedure was followed; liquid; yield 87% (130 mg); Rf (5% EtOAc – petroleum ether) 0.3; IR (neat, cm-1) νmax 3023, 1681; 1H NMR (CDCl3, 400 MHz) δ 7.89 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.36 – 7.33 (m, 3H), 7.19 – 7.17 (m, 2H), 7.14 – 7.12 (m, 3H), 7.06 – 7.02 (m, 3H), 2.58 (s, 3H);

13

C{1H} NMR (CDCl3, 100 MHz) δ 197.8,

148.1, 141.6, 139.8, 136.9, 136.0, 130.4, 130.2, 129.8, 129.0, 128.5, 128.2, 127.9, 127.7, 127.4, 26.7; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C22H18ONa 321.1255; Found 321.1259. 3ax: Methyl (E)-4-(1,2-diphenylvinyl)benzoate. General procedure was followed; white solid; yield 60% (94 mg); mp 124 – 126 °C; Rf (10% EtOAc – petroleum ether) 0.7; IR (neat, cm-1) νmax 1721, 1280; 1H NMR (CDCl3, 400 MHz) δ 7.97 (d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.4 Hz, 2H), 7.35 – 7.33 (m, 3H), 7.19 – 7.14 (m, 2H), 7.13 – 7.11 (m, 3H), 7.05 – 7.02 (m, 3H), 3.91 (s, 3H);

13

C{1H} NMR (CDCl3, 100

MHz) δ 167.1, 148.0, 141.7, 139.8, 137.0, 130.4, 130.1, 129.8, 129.6, 129.0, 128.9, 128.2, 127.8, 127.6, 127.3, 52.2; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C22H18O2Na 337.1204; Found 337.1206. 3ba: (Z)-2,2'-(1-Phenylethene-1,2-diyl)dithiophene.32d General procedure was followed; brown solid; yield 85% (114 mg); mp 78 – 80 °C; Rf (petroleum ether) 0.6; IR (neat, cm-1) νmax 3070, 2362, 849; 1H NMR (CDCl3, 400 MHz) δ 7.50 (dd , J = 5.2 Hz, J = 1.2 Hz, 1H), 7.41 – 7.37 (m, 3H), 7.32 – 7.23 (m, 3H), 7.17 – 7.15 (m, 1H), 7.11 (d, J = 5.2 Hz, 1H), 7.05 – 7.02 (m, 2H), 6.91 – 6.89 (m, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 141.7, 140.9, 139.7, 131.9, 129.9, 129.0, 128.4, 127.8, 127.7, 127.7, 127.3, 126.6, 126.3, 124.3. 3ca: Ethene-1,1-diyldibenzene.31 General procedure was followed; liquid; yield 65% (59 mg); Rf (petroleum ether) 0.8; 1H NMR (CDCl3, 400 MHz) δ 7.34 – 7.33 (m, 10H), 5.47 (s, 2H);

13

C{1H} NMR

(CDCl3, 100 MHz) δ 150.2, 141.6, 128.4, 128.3, 127.8, 114.5. 3da: Prop-1-ene-1,1-diyldibenzene and (E)-prop-1-ene-1,2-diyldibenzene.31 General procedure was followed; white solid; yield 84% (81 mg); Rf (petroleum ether) 0.5; IR (neat, cm-1) νmax 1443; 1H NMR 23 ACS Paragon Plus Environment


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(CDCl3, 400 MHz) Aromatic protons were not assigned to the individual diastereomers due to the complexity of the spectrum: α isomer δ 7.51 – 7.49 (m, 1H), 7.35 – 7.32 (m, 4H), 7.28 – 7.16 (m, 5H), 6.15 (q, 1H), 1.74 (d, 3H), β isomer δ 7.51 – 7.49 (m, 1H), 7.35 – 7.32 (m, 4H), 7.28 – 7.16 (m, 5H), 6.83 (s, 1H), 2.26 (s, 3H); 13C{1H} NMR (CDCl3, 100 MHz) δ 144.1, 143.1, 142.6, 140.1, 138.5, 137.5, 130.2, 129.3, 128.4, 128.3, 128.3, 128.2, 127.8, 127.3, 127.0, 126.8, 126.6, 126.1, 124.2, 17.6, 15.8. 3ea: Ethyl 3,3-diphenylacrylate and ethyl (Z)-2,3-diphenylacrylate. General procedure was followed; colorless liquid; yield 94% (109 mg); Rf (10% EtOAc – petroleum ether) 0.4; IR (neat, cm-1) νmax 2982, 1720, 1162; 1H NMR (CDCl3, 400 MHz): Aromatic protons were not assigned to the individual diastereomers due to the complexity of the spectrum. minor isomer δ 7.47 (d, J = 7.6 Hz, 2H), 7.36 – 7.29 (m, 7H), 7.24 – 7.20 (m, 1H), 7.03 (s, 1H), 4.26 (q, 2H), 1.18 (t, 3H); major isomer δ 7.36 – 7.29 (m, 8H), 7.24 – 7.20 (m, 2H), 6.36 (s, 1H), 4.04 (q, 2H), 1.10 (t, 3H); 13C{1H} NMR δ (CDCl3, 100 MHz): 169.7, 166.2, 156.5, 140.9, 139.1, 137.0, 135.4, 131.3, 129.4, 129.2, 128.8, 128.5, 128.4, 128.4, 128.3, 128.2, 127.9, 126.5, 117.6, 61.4, 60.1, 14.1, 13.9; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C17H16O2Na 275.1048; Found 275.1047. 3fa: 3,3-Diphenylprop-2-en-1-ol. General procedure was followed; brown solid; yield 43% (45 mg); mp 62 – 64 °C; Rf (20% EtOAc – petroleum ether) 0.3; IR (neat, cm-1) νmax 3336, 1016; 1H NMR (CDCl3, 400 MHz) δ 7.36 – 7.30 (m, 3H), 7.22 – 7.29 (m, 5H), 7.14 (d, J =6 Hz, 2H), 6.22 (t, 1H), 4.19 (d, J = 6.8 Hz, 2H), 1.88(bs, 1H);

13

C{1H} NMR (CDCl3, 100 MHz) δ 144.2, 141.9, 139.1, 129.8, 128.29,

128.27, 127.70, 127.67, 127.6, 60.7; HRMS (ESI-TOF) m/z: [M + Na]+ Calcd for C15H14ONa 233.0942; Found 233.0944. 3ga: (2,2-Diphenylvinyl)trimethylsilane.30 General procedure was followed; liquid); yield 77% (97 mg); Rf (petroleum ether) 0.8; 1H NMR (CDCl3, 400 MHz) δ 7.41 – 7.28 (m, 10H), 6.39 (s, 1H), 0.02 (s, 9H);


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13

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

C{1H} NMR (CDCl3, 100 MHz) δ 157.2, 143.4, 142.8, 129.8, 128.4, 128.3, 128.2, 128.0, 127.7,

127.5, 127.3, 0.1. 3ha: 2-(2,2-Diphenylvinyl)thiophene and (Z)-2-(1,2-Diphenylvinyl)thiophene. General procedure was followed; colorless liquid; yield 80% (105 mg); Rf (5% EtOAc – petroleum ether) 0.7; IR (neat, cm-1) νmax 3057, 1492; 1H NMR (CDCl3, 400 MHz) Aromatic protons were not assigned to the individual diastereomers due to the complexity of the spectrum. minor isomer: δ 7.46 – 7.39 (m, 3H), 7.38 – 7.27 (m, 5H), 7.25 – 7.22 (m, 2H), 7.00 – 6.95 (m, 3H), 6.85 (s, 1H); major isomer: δ 7.46 – 7.39 (m, 3H), 7.38 – 7.27 (m, 5H), 7.25 – 7.22 (m, 3H), 7.18 – 7.14 (m, 1H), 6.90 – 6.88 (m, 1H), 6.83 (s, 1H);

13

C{1H}

NMR (CDCl3, 100 MHz) δ 143.3, 141.8, 141.7, 141.4, 139.9, 139.6, 137.3, 135.3, 130.6, 130.5, 129.6, 129.4, 129.1, 128.6, 128.4, 128.3, 128.21, 128.17, 128.0, 127.7, 127.5, 127.3, 127.2, 126.9, 126.5, 126.4, 126.3, 121.0; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C18H14SH 263.0894; Found 263.0890. 3ja:

(2-(4-Methoxyphenyl)ethene-1,1-diyl)dibenzene

and

(Z)-(1-(4-Methoxyphenyl)ethene-1,2-

diyl)dibenzene. General procedure was followed; Colorless liquid; yield 85% (121 mg); Rf (5% EtOAc – petroleum ether) 0.6; IR (neat, cm-1) νmax 3024, 1249; 1H NMR (CDCl3, 400 MHz) minor isomer: δ 7.33 – 7.21 (m, 8H), 7.19 – 7.04 (m, 4H), 6.95 – 6.82 (m, 3H), 6.64 (d, J =8.8 Hz, 1H), 3.77 (s, 3H); major isomer: δ 7.33 – 7.21 (m, 8H), 7.19 – 7.04 (m, 4H), 6.95 – 6.82 (m, 3H), 6.64 (d, J =8.8 Hz, 1H), 3.68 (s, 3H);

13

C{1H} NMR (CDCl3, 100 MHz) δ 159.1, 158.5, 143.9, 143.7, 142.4, 140.8, 140.7,

137.8, 132.6, 131.7, 130.9, 130.5, 130.2, 129.6, 128.8, 128.4, 128.3, 128.1, 127.9, 127.8, 127.8, 127.6, 127.5, 127.4, 127.3, 126.7, 114.1, 113.5, 55.2, 55.2; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C21H18OH 287.1436; Found 287.1431. 3ka: (2-(4-Nitrophenyl)ethene-1,1-diyl)dibenzene General procedure was followed; Yellow solid; yield 20% (40 mg); Rf (5% EtOAc – petroleum ether) 0.5; IR (neat, cm-1) νmax 3436, 1341; 1H NMR (CDCl3, 400 MHz) δ 7.97 (d, J =9.2 Hz, 2H), 7.37 – 7.34 (m, 8H), 7.18 – 7.12 (m, 4H), 6.99 (s, 1H); 13C{1H} NMR (CDCl3, 100 MHz) δ 147.2, 146.1, 144.4, 142.5, 139.4, 130.3, 130.1, 129.1, 128.6, 128.5, 128.4, 25 ACS Paragon Plus Environment


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128.0, 125.9, 123.5; HRMS (ESI-TOF) m/z: [M + H]+ Calcd for C20H15NO2H 302.1181; Found 302.1180. ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI: Preliminary mechanistic controls, 1H NMR and 13C spectra for all compounds (PDF). AUTHOR INFORMATION Corresponding Author * E-mail: [email protected]. Notes The authors declare no competing financial interests. ACKNOWLEDGMENTS This work was supported by SERB (EMR/2016/006358),

New-Delhi, CSIR (No. 02(0226)15/EMR-

II), New-Delhi, Indian Institute of Science, and R. L. Fine Chem. We thank Dr. A. R. Ramesha (R. L. Fine Chem) for useful discussion. SR thanks UGC for a fellowship. REFERENCES (1) Neeve, E. C.; Geier, S. J.; Mkhalid, I. A. I.; Westcott, S. A.; Marder, T. B. Diboron(4) Compounds: From Structural Curiosity to Synthetic Workhorse. Chem. Rev. 2016, 116, 9091–9161. (2) Wei, C. S.; Davies, G. H. M.; Soltani, O.; Albrecht, J.; Gao, Q.; Pathirana, C.; Hsiao, Y.; Tummala, S.; Eastgate, M. D. The Impact of Palladium(II) Reduction Pathways on the Structure and Activity of Palladium(0) Catalysts. Angew. Chem. Int. Ed. 2013, 52, 5822–5826.


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