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1st October 2014 @ 11:06

Palladium catalysed coupling of JU 26 and JU 29-1 (boronic ester) to form the fluoroalkene.  

Github issue:

Literature ref:

Reaction Scheme

Procedure

Started 4:30pm

JU 26 (~20-30 mg, flask was washed out, 0.1-0.15 mmol, 1 equiv), JU 29-1 (85 mg, 0.3 mmol, 2 equiv), potassium carbonate (104 mg, 0.75 mmol, 6 equiv) were stirred into toluene (3.75 mL), ethanol (0.75 mL) and water (0.75 mL). 2 balloons of argon were bubbled through to remove oxygen. 1,4-Bis(diphenylphosphino)butane-palladium(II) chloride (12 mg, 0.02 mmol, 0.2 equiv) was added and the mixture heated at reflux overnight. 

 

HIRAC

HIRAC JU 31-1.pdf

InChI strings

InChI=1S/C11H15BBrNO2/c1-10(2)11(3,4)16-12(15-10)8-6-5-7-9(13)14-8/h5-7H,1-4H3

and

InChI=1S/C8H6BrF/c9-8(10)6-7-4-2-1-3-5-7/h1-6H/b8-6-

to

InChI=1S/C13H9BrFN/c14-13-8-4-7-12(16-13)11(15)9-10-5-2-1-3-6-10/h1-9H/b11-9-

SMILES

BrC1=CC=CC(B2OC(C)(C)C(C)(C)O2)=N1

and

BrC(F)=[S=I]CC[4]=CC=CC=C@5

to

BrC1=CC=CC(/C(F)=C/C2=CC=CC=C2)=N1

Attached Files
22nd September 2014 @ 00:27

Palladium catalysed coupling of (2-bromovinyl)benzene and JU 29-1 (boronic ester) to form a basic alkene.  

Github issue:

Literature ref:

Reaction Scheme

Procedure

Started 4:30pm

(2-bromovinyl)benzene (100 mg, 0.55 mmol, 1 equiv), JU 29-1 (200 mg, 0.7 mmol, 1.3 equiv), potassium carbonate (228 mg, 1.65 mmol, 3 equiv) were stirred into toluene (7.5 mL), ethanol (1.5 mL) and water (1.5 mL). 2 balloons of argon were bubbled through to remove oxygen. 1,4-Bis(diphenylphosphino)butane-palladium(II) chloride (18 mg, 0.03 mmol, 0.05 equiv) was added and the mixture heated at reflux overnight. 

 

HIRAC

HIRAC JU 30-1.jpeg
HIRAC JU 30-1 1.jpeg

InChI strings

InChI=1S/C11H15BBrNO2/c1-10(2)11(3,4)16-12(15-10)8-6-5-7-9(13)14-8/h5-7H,1-4H3

and

InChI=1S/C8H7Br/c9-7-6-8-4-2-1-3-5-8/h1-7H/b7-6+

to

InChI=1S/C13H10BrN/c14-13-8-4-7-12(15-13)10-9-11-5-2-1-3-6-11/h1-10H/b10-9+

SMILES

BrC1=CC=CC(B2OC(C)(C)C(C)(C)O2)=N1

and

Br/C=C/C1=CC=CC=C1

to

BrC1=CC=CC(/C=C/C2=CC=CC=C2)=N1


Attached Files
22nd September 2014 @ 00:22

Palladium catalysed coupling of B-bromostyrene and phenylboronic acid to form basic alkene to test reaction conditions. 

Github issue:

Literature ref:

Reaction Scheme

Procedure

Started 11am 29/09/14

B-bromostyrene (100 mg, 0.55 mmol, 1 equiv), phenylboronic acid (80 mg, 0.66 mmol, 1.2 equiv), potassium carbonate (230 mg, 1.65 mmol, 3 equiv) were stirred into toluene (7.5 mL), ethanol (1.5 mL) and water (1.5 mL) under nitrogen before adding Pd(dppb)Cl2 (18 mg, 0.03 mmol, 0.05 equiv) and heating at relux for 6 h. The solution was pale yellow in colour. Analysis by TLC showed the reaction looked to be complete, although due to time constraints was going to be stopped anyway.

TLC JU 28-1 20:80 toluene:hexane 6 h

The solution was filtred through celite (washng through with 50 mL ethyl acetate), dried with magnesium sulfate and conentrated in vacuo. The crude was a dark green oil at room temp, solidifying when fridged over night. 

1H NMR, crude, CDCl3, 300 MHz

JU 28-1 crude 300 MHz.pdf
JU 28-1 crude.zip

The crude product was purified on the biotage isolera with hexanes and toluene.

1H NMR, pure, CDCl3, x MHz

 

HIRAC

HIRAC JU 29-1.pdf
 

InChI strings

InChI=1S/C6H7BO2/c8-7(9)6-4-2-1-3-5-6/h1-5,8-9H

and

InChI=1S/C8H7Br/c9-7-6-8-4-2-1-3-5-8/h1-7H/b7-6+

to

InChI=1S/C14H12/c1-3-7-13(8-4-1)11-12-14-9-5-2-6-10-14/h1-12H/b12-11+

SMILES

OB(O)C1=CC=CC=C1

and

Br/C=C/C1=CC=CC=C1

to

C1(/C=C/C2=CC=CC=C2)=CC=CC=C1

Attached Files
22nd September 2014 @ 00:18

Conclusion: Since performing this reaction I have found out that i have not made the chloropyridinyl boronic ester, thsu this subsequent reaction was unsuccessful. 

Palladium catalysed coupling of JU 26-1 and 24-2 to form the fluoroalkene with alternate palladium catalyst to 27-1.

Github issue: #262

Literature ref:

Reaction Scheme

Procedure

Started 3pm

JU 26-1 (50 mg, 0.25 mmol, 1 equiv), JU 24-2 (72 mg, 0.3 mmol, 1.2 equiv), potassium carbonate (105 mg, 0.75 mmol, 3 equiv) were stirred into toluene (3.75 mL), ethanol (0.75 mL) and water (0.75 mL) under nitrogen before adding 1,4-Bis(diphenylphosphino)butane-palladium(II) chloride (8 mg, 0.013 mmol, 0.05 equiv) and heating at reflux (bath temp 90°C) overnight. Analysis by TLC showed the reaction was complete. 

TLC JU 27-2 20:80 toluene:hex overnight.JPG

The crude product was filtered through celite to remove palladium and washed through with ethyl acetate before drying in vacuo. The crude product was brown in colour (50 mg, 84%) and was purirfied using the biotage isolera (toluene/hexanes) and the 3 fractions isolated were analysed by 1H NMR. 

 

HIRAC

HIRAC JU 27-2.pdf

InChI strings

InChI=1S/C11H15BClNO2/c1-10(2)11(3,4)16-12(15-10)8-6-5-7-9(13)14-8/h5-7H,1-4H3

and

InChI=1S/C8H6BrF/c9-8(10)6-7-4-2-1-3-5-7/h1-6H/b8-6-

to

InChI=1S/C13H9ClFN/c14-13-8-4-7-12(16-13)11(15)9-10-5-2-1-3-6-10/h1-9H/b11-9-

SMILES

ClC1=CC=CC(B2OC(C)(C)C(C)(C)O2)=N1

and

F/C(Br)=C\C1=CC=CC=C1

to

F/C(C1=NC(Cl)=CC=C1)=C\C2=CC=CC=C2



Attached Files
21st September 2014 @ 23:37

Synthesis of bromopyridine boronic ester. 

GitHub link: #250

Literature ref: 10.1016/j.tet.2003.10.020

Reaction Scheme

Procedure

Started 11:15am 30/09/14

To a solution of ~1.7 M solution of n-BuLi (2.9 mL, 5.0 mmol, 1.2 equiv.) in freshly distilled tetrahydrofuran (40 mL), cooled to -78°C, was added a solution of 2,6-dibromopyridine (1.0 g, 4.2 mmol, 1 equiv.) in THF (20 mL). On addition of the 2,6-dibromopyridine the reaction mixture turned dark yellow/brown. The reaction was stirred at -78°C for 45 min. A solution of triethylborate (730 mg, 0.85 mL, 5.0 mmol, 1.2 equiv.) in THF (8 mL) was added and the dark mixture stirred at room temp for 3 h. A solution of pinacol (670 mg, 5.7 mmol, 1.35 equiv) in THF (8 mL) was added, turning the solution a golden yellow, followed by glacial acetic acid (0.25 mL, 265 mg, 4.4 mmol, 1.05 equiv) 5 minutes later.  

The mixture was filtered through celite and quenched by slow addition of 2.5% aqueous NaOH solution (100 mL). The aqueous layer was separated and acidified down to pH 6 by careful addition of 3M HCl, keeping the internal temperature below 5°C. The solution was extracted with ethyl acetate (3 x 50 mL) and the solvent removed by rotary evaporation and dried in vacuo. The crude product was an orange solid. Washing with acetonitrile was attempted as per the paper however this appeared to dissolve it instead of washing off the brown impurity (solid is reported to be white). The crude was analysed by 1H NMR and found to be the correct product. It was used without further purification in subsequent reactions.

1H NMR, crude, DMSO, 300 MHz

JU 29-1 crude 300 MHz.pdf
JU 29-1 crude.zip
 

 

HIRAC

HIRAC JU 29-1.pdf

InChI strings

InChI=1S/C5H3Br2N/c6-4-2-1-3-5(7)8-4/h1-3H

to

InChI=1S/C11H15BBrNO2/c1-10(2)11(3,4)16-12(15-10)8-6-5-7-9(13)14-8/h5-7H,1-4H3

SMILES

BrC1=CC=CC(Br)=N1

to

BrC1=CC=CC(B2OC(C)(C)C(C)(C)O2)=N1

Attached Files