new developments in pd(ii)-catalysed cyclisations of aminoalkenitols dr. peter szolcsányi...
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New Developments inNew Developments inPd(II)Pd(II)--Catalysed CyclisationsCatalysed Cyclisations
of Aminoalkenitolsof Aminoalkenitols
Dr. Peter SzolcsányiDepartment of Organic ChemistrySlovak University of Technology
Bratislava, Slovak Republic
Pd(II)-Catalysed chlorocyclisation and N,O-bicyclisation
of polyhydroxylated aminoalkenitols
Synthetic versatility of chloromethyl piperidines
Where did the idea come from ?
P. Szolcsányi et al.: Tetrahedron: Asymmetry 2000, 11, 2579-2597.
Known precedents of Pd(II)/CuCl2-catalysedchloroaminocyclisation
M. Wada, H. Aiura, K. Akiba: Heterocycles 1987, 26, 929-934.
A. Lei, X. Lu, G. Liu: Tetrahedron Lett. 2004, 45, 1785-1788.
Preparation of substrates - D-gluco compound
Preparation of substrates - D-galacto compound
Pd(II)/CuCl2-catalysed chlorocyclisation-D-gluco serie
Entry Solvent Time & TemperatureIsolated yield
(after FLC)HPLC ratio of
L-ido / D-gluco (d.e.)
1 AcOH 48 hrs, 23oC 70% 19 / 1 (90%)
2 DMF 24 hrs, 30oC 21% 8 / 1 (82%)
3 CH2Cl2 24 hrs, 30oC 65% 6 / 1 (71%)
4 THF 24 hrs, 30oC 60% 6 / 1 (71%)
5 MeOH 24 hrs, 23°C 59% 5 / 1 (67%)
6 Toluene 48 hrs, 30oC 56% 3 / 1 (33%)
Pd(II)/CuCl2-catalysed chlorocyclisation-D-galacto serie
Entry Solvent Catalyst & Additive(s)Time &
TemperatureChlorides/bicycle (yield after FLC)
HPLC ratio ofL-altro/D-gala
(d.e.)
1 AcOH 0.1 eq. PdCl2, 3 eq. CuCl2, 3 eq. AcONa 24 hrs, 25oC 28% / 49% 19 / 1 (90%)
2 DMF - detto - 19 hrs, 25oC 53% / 11% 15 / 1 (88%)
3 CH2Cl2 - detto - 24 hrs, 29oC 36% / 8% 5 / 1 (67%)
4 THF - detto - 24 hrs, 25oC 54% / 10% 2 / 1 (33%)
5 Toluene - detto - 24 hrs, 29oC 43% / 9% 1 / 2 (33%)
6 MeOH - detto - 24 hrs, 25oC 32% / 7% 1 / 3 (50%)
7 AcOH 0.1 eq. PdCl2, 2 eq. CuCl2, 2 eq. AcONa 48 hrs, 30oC 35% / 52% 19 / 1 (90%)
8 AcOH 0.1 eq. PdCl2, 1 eq. CuCl2, 1 eq. AcONa 48 hrs, 28oC 25% / 48% 19 / 1 (90%)
9 AcOH 0.1 eq. PdCl2, 3 eq. CuCl2 24 hrs, 30oC 27% / 50% 19 / 1 (90%)
10 AcOH 1 eq. PdCl2, 3 eq. AcONa 96 hrs, 28oC 0% / 0% -
11 AcOH 0.1 eq. Pd(OAc)2, 2 eq. BQ, 3 eq. AcONa 24 hrs, 30oC - / 0% -
Mechanistic proposal of the Pd(II)/CuCl2-catalysedchloroaminocyclisation and bicyclisation
Synthesis of new analogues of iminoalditols
H. Takahata, Y. Banba, H. Ouchi, H. Nemoto: Org. Lett. 2003, 5, 2527-2529.
New type of the Pd(II)/CuCl2-catalysed bicyclisation ???
Analogous to: T. M. Cokley et al.: Tetrahedron Lett. 1996, 37, 1905-1908.
Preparation of model substrate for the bicyclisation
OH
NHR
NR
Ocat. Pd(II)-saltn eq.CuCl2
n eq. AcONasolvent(s)
Model screening of Pd(II)/CuCl2-catalysed bicyclisation
Entry Solvent Catalyst & Additive(s) Time & Temperature Yield after FLC
1 AcOH 0.1 eq. PdCl2, 3 eq. CuCl2, 3 eq. AcONa 20°C, 24 hrs 45%
2 AcOH 0.2 eq. Pd(OAc)2, 3 eq. Cu(OAc)2 30°C, 48 hrs Complex mixture
3 THF 0.2 eq. PdCl2, 1.1 eq. BQ, 2 eq. LiCl 45°C, 48 hrs Complex mixture
4 AcOH 0.1 eq. PdCl2, 3 eq. CuCl2 35°C, 24 hrs 71%
5 AcOH 0.1 eq. PdCl2, 2 eq. CuCl2 40°C, 48 hrs 65%
6 AcOH 0.1 eq. PdCl2, 1 eq. CuCl2 40°C, 48 hrs 74%
7 CH2Cl2 0.1 eq. PdCl2, 2 eq. CuCl2 35°C, 22 hrs 71%
8 THF 0.1 eq. PdCl2, 2 eq. CuCl2 35°C, 22 hrs 47%
9 AcOH 0.1 eq. Pd(OAc)2, 2 eq. CuCl2 40°C, 12 hrs 64%
10 AcOH 0.1 eq. PdCl2(MeCN)2, 2 eq. CuCl2 40°C, 12 hrs 69%
11 AcOH 1 eq. PdCl2 40°C, 26 hrs 0%
Mechanistic proposal of Pd(II)/CuCl2-catalysed bicyclisation
P. Szolcsányi, T. Gracza: Chem. Commun. 2005, 3948-3950.
Acknowledgments
Generous support Prof. Dr. Tibor Gracza
HPLC Dr. Katarína Hroboňová
NMR Dr. Naďa Prónayová
IR Ms. Silvia Markusová
MALDI Dr. Ivan Špánik
Grant APVT-20-000904