KBS28-4 - Click coupling of 1-azido-naphthyl and propargyl alcohol

[KlementineJBS]

Link to HIRAC and master page #170. Original method can be found in J. Batten's PhD thesis (2022).

KBS28 - Click coupling with 1-azidonaphthalene and propargyl alcohol.docx

Previous attempt is #60 - this was done with CuSO4

This attempt uses CuI and MeCN - logic is that compound was likely not dissolving well in the THF/water combination required for the CuSO4 conditions. Conditions are taken from Elva Shi's MPhil thesis.

Reaction scheme

Outcome

164.3 mg, 0.730 mmol, 81%

total reaction time: 40 hrs

[KlementineJBS]

1. Added CuI (21.2 mg, 0.111 mmol, 0.1 equiv.) and sodium ascorbate (92.5 mg, 0.5 equiv.) to a flask
2. Vacuumed and backfilled with N2 x 3
3. Added DIPEA (0.17 mL, 0.99 mmol, 1.1 equiv.)
4. Added propargyl alcohol (57 uL, 1.1 equiv.) and SM (152 mg, 0.900 mmol) dissolved in MeCN (3 mL)
5. Left stirring at rt from 4.15 pm

TLC at 5 pm indicated SM was present, no sign of product but this may be due to aliquot being too dilute.

6. Added more MeCN (2 mL)

[KlementineJBS]

17.10.23

At 11 am TLC indicated reaction was progressing but not yet complete.

7. Added another 1.1 equivalents of propargyl alcohol dissolved in 2 mL MeCN.

TLC still indicated that reaction was not complete at 5 pm.

8. Added another 1.1 equivalents DIPEA

[KlementineJBS]

TLC today finally suggested reaction was complete.

Diluted with water (15 mL) and extracted with DCM (4 x 10 mL), washed with water (2 x 10 mL) and dried over Mag sulphate.

Vial: 15.7707 Full vial: 15.9350 Mass: 164.3 mg, 0.730 mmol, 81%

[KlementineJBS]

H NMR

NMR suggests formation of product. Some propargyl alcohol remains (peaks at 4.27, 2.48, 2.37) as well as solvent (MeCN). Sample was dried further prior to yield calculations.

KBS28-4 cr.pdf KBS28-4 cr_1.zip

[KlementineJBS]

The silica plug was rinsed with ethyl acetate and NMR'd but doesn't appear to be any recognisable compound.

KBS23-5 side product_1.zip