Heterogeneous Aquacatalysis Toward Ideal Organic Synthesis
Yasuhiro Uozumi
Institute for Molecular Science and CREST, Okazaki 444-8787, JAPANWe have recently developed palladium and rhodium complexes of amphiphilic polystyrenepoly(ethylene glycol) (PS-PEG) resin-supported phosphine ligands (Figure 1) which promotevarious catalytic transformations smoothly in water under heterogeneous conditions.

Thepalladium-catalyzed π-allylic substitution, carbonylation, Heck reaction, Suzuki-Miyaura coupling,Sonogashira coupling, cycloisomerization, and rhodium-catalyzed alkyne-cyclotrimerization,hydroformylation, and Michael addition are representatives where the advantages of both aqueousand heterogeneous-switching were combined in one system to achieve high level of chemicalgreenness.

CH3O

H2NOn

On

O
CH2NH2PSPEGPhPh

Phn

PSPEGO
H
N C

NH2m

PPh2

APSPEG

PPh2
B

N
PPh2

Figure 1. A typical structures of PS-PEG resin (left top) and the polymer-supported phosphines (A and B),
and a SEM image of PS-PEG resin beads (right).

A fully environmentally benign multi-step asymmetric organic synthesis of a hydrindaneframework was achieved in water under mild conditions with recyclable polymeric catalysts torepresent what may be considered an ideal chemical process. Here we report the development offully environmentally benign heterogeneous aquacatalytic multi-step asymmetric organic synthesis.
Asymmetric synthesis of the hydrindane (3aR,7aS)-4 was achieved in water with recyclable
catalysts. The racemic cyclohexenyl ester rac-1 reacted with diethyl malonate in water with a PSPEG resin-supported chiral imidazoindole phosphine-Pd complex A (10 mol%) to give 90% ee of 2.
The polymeric chiral palladium complex was reused three times without any loss ofstereoselectivity. Propargylation of the cyclohexenylmalonate 2 was performed with PS-PEGimmobilized PTC base B to give a quantitative yield of the 1,6-enyne (S)-3.

The enyne (S)-3underwent cycloisomerization with the amphiphilic polymeric palladium C to afford hydrindane(3aR,7aS)-4 in 94% yield.
HMeOOCOOCOOMerac-1+CH2(COOEt) 2A (cat)
Li2CO3, H2O

Br(S )-3

1st use: 100% yield
2nd use: 99% yield
3rd use: 100% yield(S )-2
1st use: 92% yield
90% ee2nd use: 89% yield
90% ee
3rd use: 90% yield
90% eeC (cat)HCOOH
COOEt H2O
COOEt

B
H2OO

COOEt
COOEt
PSOO
O n N C (CH 2)3HN

APSO

O n NBu 3OH

OO
O n N CH

HNPdP
Ph2

BPhH

H
EtOOC
(3aR,7aS )-4
COOEt
1st use: 94% yield
2nd use: 94% yield
3rd use: 93% yield

Ph2
PO

PdPSOOHN COnP
Ph2PhC[selected recent reference papers reported from the author’s group](a) Uozumi, Y. Top. Curr. Chem. 2004, 242, 7 (review). (b) Yamada, Y. M. A.; Arakawa, T.;
Hocke, H.; Uozumi, Y. Angew. Chem. Int. Ed. 2007, 46, 704 (catalytic oxidation). (c) Uozumi, Y.;
Yamada, Y. M. A.; Beppu, T.; Fukuyama, N.; Ueno, M.; Kitamori, T. J. Am. Chem. Soc. 2006, 128,15994 (catalytic membrane). (d) Yamada, Y. M. A.; Maeda, Y.; Uozumi, Y. Org. Lett. 2006, 8,4259 (network polymeric complex). (e) Uozumi, Y.; Suzuka, T. J. Org. Chem. 2006, 71, 8644
(asymmetric C1 substitution). (f) Uozumi, Y.; Suzuka, T.; Kawade, R.; Takenaka, H. Synlett 2006,
2109 (allylic azidation). (g) Kobayashi, Y.; Tanaka, D.; Danjo, H.; Uozumi, Y. Adv. Synth. Catal.
2006, 348, 1561 (combinatorial catalyst). (h) Nakai, Y.; Kimura, T.; Uozumi, Y. Synlett 2006,
3065 (alkylative cyclization). (i) Uozumi, Y.; Kimura, M. Tetrahedron Asymmetry 2006, 17, 161(asymmetric etherification). (j) Yamada, Y. M. A.; Uozumi, Y. Org.Lett. 2006, 8, 1375 (viologenpolymer). (k) Nakai, Y.; Uozumi, Y. Org. Lett. 2005, 7, 291 (multi-step synthesis). (l) Nakao, R.;Rhee, H.; Uozumi, Y. Org. Lett. 2005, 7, 163 (nano-Pd catalysis). (m) Uozumi, Y.; Tanaka, H.;
Shibatom, K. Org. Lett. 2004, 6, 281 (asymmetric amination). (n) Uozumi, Y.; Nakao, R. Angew.
Chem., Int. Ed. 2003, 115, 204 (nano-Pd catalysis). (o) Uozumi, Y.; Nakai, Y. Org. Lett. 2002, 4,2997 (HTS coupling).
(asymmetric alkylation).

(p) Uozumi, Y.; Shibatom, K. J. Am. Chem. Soc. 2001, 123, 2919