DOMINO CO - ANR
1
DOMINO CO Allylation / carbonylations domino reactions : concept and applications CP2D 2008 Programme + year (e.g. CP2D 2009) CONTACT : Prof. André Mortreux ENSCL BP 90108 59652 Villeneuve d’Ascq Cedex [email protected] André Mortreux (coordinator), Mathieu Sauthier, Yves Castanet, Hélène Bonin UCCS, UMR CNRS 8181 Catalyse et Chimie Moléculaire, ENSCL/USTL, 59652 Villeneuve d’Ascq Cedex Giovanni Poli, Frédéric Liron, Guillaume Prestat UPMC, Synthèses Sélectives et Organométalliques, IPCM, 75252 Paris Cedex Work carried out by Benoit Wahl (Lille) and Steven Giboulot (Paris) PhD students funded by the ANR In the frame of the CP2D ANR project DOMINO-CO, we developed two carbonylative palladium-catalyzed pseudo-domino type I sequences. The former, studied in Lille, involved an alkoxycarbonylation / allylation succession, whereas the latter, studied in Paris, entailed an allyloxycarbonylation / decarboxylative allylation chain. Both sequences start from readily available α- chloroketones and share the generation of intermediate β-ketoesters. Such sequences fulfill atom economy (use of CO and catalysis) as well as step economy (domino) requirements, and represent a considerable challenge, as only the fine and judicious tuning of the reaction conditions and the design of the ligand may render compatible the two steps on the same catalyst allowing to obtain the desired concatenated catalysis in a single synthetic operation. Pd R O Cl L R Pd O O Cl L Pd 0 L 2 CO M e OH PdL 2 X X R OM e O O R OM e O O + B ase + BH + B ase + BH Cl R O R OM e O O Pd ( 0 ) L 2 L L R O Cl CO ( 15 b ar ) R'OH + NB u 3 ( 4 . 5 e q ) OPh R O O O R' Pd ( acac )2 1 mo l% 2 . 5 e q R O O O R' + X an t p h os 2 mo l% 90 °C, 15 h H 1 2 Carbonylation / allylation 1 2 Cl O Cl O Cl Cl O F N O Cl Ph Cl O 62% 0% 23% 55% 37% 39% 1 2 1 2 30% 54% 65% 5% 53% 20% 23% - - - Cl O Cl O Ph Cl O Yi e ld s i n t o mono ( 1 ) an d di su b s tit u t e d ( 2 ) a ll y l a ti on p ro d uc t s + OPh Pd ( acac )2 ( 1 mo l% ) X an t p h os ( 2 mo l% ) R' OH ( 10 m L ) 1 e q 2,5 e q O Cl CO ( 15 b ars ) NB u 3 ( 4 . 5 é q ) 90 °C, 16 h 1 : n = 1 2 : n = 2 O R' O O Ph n Generalization to other alcohols 1 2 M e OH OH OH 12% 84% 14% 85% 10% 73% Wahl, B.; Bonin, H.; Mortreux, A.; Giboulot, S.; Liron, F.; Poli, G.; Sauthier, M. Adv. Synth. Catal., DOI: 0.1002/adsc.201200378 Wahl, B.;Giboulot, S.; Mortreux, A.; Castanet, Y.; Sauthier, M.; Liron, F.; Poli, G. Adv. Synth. Catal., 2012, 1077-1083. Giboulot, S.; Liron, F.; Prestat, G.; Wahl, B.; Sauthier, M.; Castanet, Y.; Mortreux A.; Poli, G. Chem. Commun. 2012, 48, 5889-5891. N-Allylation / Carbopalladation / Carbonylation I N H T s [ Pd ] ( 10 mo l% ) P ( 2 - f ur ) 3 ( 40 mo l% ) n- B u 4 NB r ( 1 . 3 e q u i v. ) K 2 CO 3 ( 5 e q u i v. ) CO ( 1 a t m ) t o l uene / me th ano l ( 2/1 ) 95 °C, 3 h CO 2 M e B r + 52% N T s CO 2 M e O OM e O OM e B r O OM e [ Pd ] B r N T s O M e O [ Pd ] O I N T s [ Pd ] O M e O I [ Pd ] N T s O OM e X I N H T s I N T s O OM e B ase· HB r + N T s O M e O O OM e + B ase· HI [ Pd ( 0 )] N - ALLYLATION CARBOPALLADATION CARBONYLATION + M e OH B ase I II III IV s t ar t h ere CO A r O Cl [ Pd ( 0 )] A r [ Pd ] Cl O A r O [ Pd ] Cl O OH H [ Pd ] Cl B ase B ase· HCl A r O O O A r O O O A r O O [ Pd ] O A r O OCO CARBONYLATIVE CYCLE 1 rs t s t e p DECARBOXYLATIVE CYCLE 2 n d s t e p CO [ Pd ( 0 )] + s t ar t h ere P O 3 O Cl Pd ( OA c )2 ( 10 mo l % ) P ( 2 - f ur )3 ( 40 mo l % ) n- B u 3 N ( 1 . 5 e q u i v. ) , CO ( 20 b ar ) a ll y l a l co h o l ( 15 e q u i v. ) T o l uene , 130 °C, 2 h R O R R 1 R 1 R = p - t - B u , p - CN, p - Cl, p - CO 2 M e , p - M e , p - OM e , p - F, o- OM e , o- F, 2,4 - Cl 2 R 1 = H, Ph 31 - 77% OH + O PPh 2 PPh 2 XANTPHOS tri(2-furyl) phosphine Carbonylative / decarboxylative allylation R [ Pd ( 0 )] ca t CO , R 1 OH R O OR 1 LG O OR 1 R O CARBONYLATION DECARBOXYLATIVE ALLYLATION R 1 = a lk y l R 1 = a ll y l Lill e P ar i s R 2 R 2 R' - HH a l - CO 2 ALLYLATION Lill e an d P ar i s O H a l R O O CARBONYLATION CYCLE 1 st step ALLYLATION CYCLE 2 nd step
Transcript of DOMINO CO - ANR
DOMINO CO Allylation / carbonylations domino reactions : concept and applications
CP2D 2008 Programme + year (e.g. CP2D 2009)
CONTACT : Prof. André Mortreux
ENSCL BP 90108 59652 Villeneuve d’Ascq Cedex
André Mortreux (coordinator), Mathieu Sauthier, Yves Castanet, Hélène Bonin UCCS, UMR CNRS 8181 Catalyse et Chimie Moléculaire, ENSCL/USTL, 59652 Villeneuve d’Ascq Cedex Giovanni Poli, Frédéric Liron, Guillaume Prestat UPMC, Synthèses Sélectives et Organométalliques, IPCM, 75252 Paris Cedex Work carried out by Benoit Wahl (Lille) and Steven Giboulot (Paris) PhD students funded by the ANR
In the frame of the CP2D ANR project DOMINO-CO, we developed two carbonylative palladium-catalyzed pseudo-domino type I sequences. The former, studied in Lille, involved an alkoxycarbonylation / allylation succession, whereas the latter, studied in Paris, entailed an allyloxycarbonylation / decarboxylative allylation chain. Both sequences start from readily available α-chloroketones and share the generation of intermediate β-ketoesters. Such sequences fulfill atom economy (use of CO and catalysis) as well as step economy (domino) requirements, and represent a considerable challenge, as only the fine and judicious tuning of the reaction conditions and the design of the ligand may render compatible the two steps on the same catalyst allowing to obtain the desired concatenated catalysis in a single synthetic operation.
PdR
OClL
R Pd
O O
ClL
Pd0L2
CO
MeOH
PdL2X
X
R OMe
O O
R
OMe
O
O
+ Base
+ BH
+ Base
+ BH
ClR
O
R
OMe
O
OPd(0)L2
L
L
R
OCl
CO (15 bar)
R'OH
+NBu3 (4.5 eq)
OPh R O
OOR'
Pd(acac)2 1 mol%
2.5 eq
R O
OOR'
+
Xantphos 2 mol%
90 °C, 15 h
H
1 2
Carbonylation / allylation
1 2
ClO
ClO
Cl
ClO
F
N
OCl
Ph
ClO
62% 0%
23% 55%
37% 39%
1 2 1 2
30% 54%
65% 5%
53%
20%
23%
-
-
-
ClO
ClO
Ph
ClO
Yields into mono (1) and disubstituted (2) allylation products
+ OPh
Pd(acac)2 (1mol%)Xantphos (2 mol%)R'OH (10 mL)
1eq 2,5eq
OCl CO (15 bars)
NBu3 (4.5 éq)90 °C, 16 h
1 : n = 12 : n = 2
OR'
O O
Phn
Generalization to other alcohols 1 2
MeOH
OH
OH
12% 84%
14% 85%
10% 73%
Wahl, B.; Bonin, H.; Mortreux, A.; Giboulot, S.; Liron, F.; Poli, G.; Sauthier, M. Adv. Synth. Catal., DOI: 0.1002/adsc.201200378 Wahl, B.;Giboulot, S.; Mortreux, A.; Castanet, Y.; Sauthier, M.; Liron, F.; Poli, G. Adv. Synth. Catal., 2012, 1077-1083. Giboulot, S.; Liron, F.; Prestat, G.; Wahl, B.; Sauthier, M.; Castanet, Y.; Mortreux A.; Poli, G. Chem. Commun. 2012, 48, 5889-5891.
N-Allylation / Carbopalladation / Carbonylation
I
NH
Ts
[Pd] (10 mol%)P(2-fur)3 (40 mol%)
n-Bu4NBr (1.3 equiv.)K2CO3 (5 equiv.)CO (1 atm)toluene/methanol (2/1)95 °C, 3 h
CO2Me
Br+
52%
NTs
CO2Me
O
OMe
O
OMe
Br
O
OMe[Pd]
Br
NTs
OMeO
[Pd]
O
I
NTs
[Pd]
OMeO
I
[Pd]
NTs O
OMe
X
I
NH
TsI
NTs
O OMe
Base·HBr+
NTs
OMeO
O
OMe+ Base·HI
[Pd(0)]
N-ALLYLATION
CARBOPALLADATION
CARBONYLATION
+ MeOHBaseI
II
III
IV
start here
CO
Ar
OCl
[Pd(0)]
Ar [Pd]ClO
Ar
O
[Pd]Cl
O
OH
H[Pd]ClBase
Base·HCl
Ar
O
O
O
Ar
O
O
O
Ar
O
O[Pd]
O
Ar
OOCO
CARBONYLATIVE CYCLE 1rst step
DECARBOXYLATIVE CYCLE 2nd step
CO
[Pd(0)]
+
start here
PO
3
OCl
Pd(OAc)2 (10 mol %)P(2-fur)3 (40 mol %)
n-Bu3N (1.5 equiv.), CO (20 bar)allyl alcohol (15 equiv.)Toluene, 130 °C, 2 h
R
O
RR1 R1
R = p-t-Bu, p-CN, p-Cl, p-CO2Me, p-Me, p-OMe, p-F, o-OMe, o-F, 2,4-Cl2R1 = H, Ph
31-77%
OH +
O
PPh2
PPh2
XANTPHOS
tri(2-furyl) phosphine
Carbonylative / decarboxylative allylation
R
[Pd(0)] catCO, R1OH
R
O
OR1LG
O
OR1
R
O
CARBONYLATION
DECARBOXYLATIVEALLYLATION
R1 = alkyl R1 = allyl
Lille Paris
R2R2
R'
-HHal
-CO2
ALLYLATION
Lille and Paris
OHal
R
O O
CARBONYLATION CYCLE 1st step
ALLYLATION CYCLE 2nd step
