Beilstein J. Org. Chem. 2011, 7, 1441–1448.
Experimental
General procedure for azido iodination of alkenes 2
under flow conditions
In the third step, a solution of TMSN3 (6.0 mL, 45.5 mmol) in
20 mL of dry CH2Cl2 was pumped through the reactor at a flow
rate of 0.10 mL/min. Finally, the reactor was washed with
A glass reactor (12 cm length and 8.5 mm internal diameter) 20 mL of CH2Cl2 at a flow rate of 0.5 mL/min.
was filled with polymer-bound iodate(I) complex 5 (5 g; theo-
retical loading = 3.5 mmol/g) and protected from light with General procedure for the copper-catalyzed
aluminum foil. The reactor (void volume: 4.5 mL) was Huisgen-type cycloaddition under flow conditions
connected to the pump and, at the outlet side, to a collection A glass reactor (12 cm length and 8.5 mm internal diameter)
flask. The system was first flushed with dry CH2Cl2 (8 mL, packed with copper turnings (12 g) was encased within the
0.5 mL/min). Then, a solution of styrene (2a) (364 mg, inductor. The reactor was connected to the pump and, at the
3.5 mmol) in dry CH2Cl2 (17.5 mL) was pumped through the outlet side, to a collection flask. The system was flushed with
reactor at a flow rate of 0.04 mL/min. Then, 10 mL of CH2Cl2 DMF (flow rate 0.04 mL/min), and the temperature was
was used to wash the reactor (5 mL, 0.04 mL/min + 5 mL, adjusted to 70 °C regulating the PMW (pulse-width
0.5 mL/min). Product 3a (936 mg, 3.4 mmol, 98%) was directly modulation). A sample loop was filled with a solution of vinyl
obtained after evaporation of the combined organic phases.
azides 4 (0.3 mmol, 1 equiv) and alkynes 11 (0.45 mmol, 1.5
equiv) in DMF (0.5 mL). After the flow and temperature values
reached a steady state, the solution was pumped through the
system. Washing was continued until no product was detected
General procedure for the two-step preparation of
vinyl azides 4 under flow conditions
A glass reactor (12 cm length and 8.5 mm internal diameter) at the outlet as judged by TLC. The resulting solution was
filled with polymer-bound iodate(I) complex 5 (5 g; theoretical diluted with 50 mL of ethyl acetate and washed with water and
loading = 3.5 mmol/g) and a second identical flow reactor, brine (3 × 60 mL). The organic layers were dried over anhy-
which was filled with a slurry of polystyrene-bound 1,8-diaza- drous MgSO4 and evaporated under vacuum. The crude pro-
[5.4.0]bicyclo-7-undecene (8) (4 g; theoretical loading = duct was then purified by flash chromatography (petroleum
1.15 mmol/g) in dry CH2Cl2 (5 mL), were telescoped and ether/ethyl acetate) to yield the pure products 12.
protected from light with aluminum foil. The system was
connected to the pump and, at the outlet side, to a collection
Supporting Information
flask. After priming with CH2Cl2 (10 ml), a solution of styrene
(2a) (364 mg, 3.5 mmol) in dry CH2Cl2 (17.5 mL) was flushed
The Supporting Information provides details on individual
at 0.04 mL/min. Then, 10 mL more of CH2Cl2 was pumped
reactions and analytical data.
through the reactor (5 mL, 0.04 mL/min + 5 mL, 0.5 mL/min).
Supporting Information File 1
The crude product 4a (462 mg, 3.2 mmol, 91%) was isolated
after evaporation of the solvent. If necessary (see Supporting
chromatography (petroleum ether/ethyl acetate).
Details on individual reactions and analytical data.
Regeneration of functionalized polymer-bound
iodate(I) complex 5 under flow conditions
Acknowledgements
The reactor with azide-loaded ion-exchange resin 9 (5 g; theo- This work was supported by the Fonds der Chemischen Indus-
retical loading = 3.5 mmol/g) was connected to the pump and, trie. We thank Henkel AG & Co. KGaA (Düsseldorf,
at the outlet side, to a collection flask. The system was first Germany), Evonik Degussa GmbH (Essen, Germany) and IFF
flushed with water (10 mL, 0.5 mL/min). A solution of NaI GmbH (München, Germany) for financial or technical support.
(15.7 g, 105 mmol) in water (20 mL) was pumped through the We thank Fabien Coudray and Victor Olmos for experimental
reactor at flow rate of 0.15 mL/min. Then the reactor was support.
successfully washed with 10mL each of water, acetone and
References
1. L'Abbé, G. Angew. Chem. 1975, 87, 831–838.
finally with CH2Cl2 at a flow rate of 0.5 mL/min.
In the second step the system was flushed with a solution of
Angew. Chem., Int. Ed. Engl. 1975, 14, 775–782.
PhI(OAc)2 (8.5 g, 26.3 mmol) in 60 mL of dry CH2Cl2 at a
flow rate of 0.06 mL/min. Then, the reactor was washed with
2. Zou, H.; Zhu, H.; Shao, J.; Wu, J.; Chen, W.; Giulianotti, M. A.; Yu, Y.
20 mL of CH2Cl2 at a flow rate of 0.5 mL/min.
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