and F rings of strychnine in one single step. In addition, intermediate 93 was
transformed in one single step to strychnine 94 (Scheme 37) [56].
4.3 Metal-Induced Cyclisations
4.3.1 Palladium-Promoted Cyclisation
Palladium plays a crucial role in organic synthesis for the formation of single or
multiple C–C bonds from aryl derivatives. Intramolecular Heck reaction has been
particularly useful to access seven-membered rings. Nielsen et al. have studied the
regioselectivity of these reactions from unsubstituted substrates and found that the
regioselectivity depends on the nature of phosphine ligands utilised [57]. A moderate
selectivity in favour of the oxepin 97 was thus observed with S-Phos (Scheme 38).
The Heck reaction has been particularly investigated to access pharmaceutically
active compounds such as olopatadine hydrochloride, an anti-allergic drug
(Scheme 39) [58, 59]. When 98 was treated with Pd(0) in the presence of
formic acid and piperidine, oxepin 99, precursor of olopatadine, was isolated in
47 % yield.
O
Me
O
TIPSO
BOMO
H
CHO
KHMDS
THF
-78 °C to rt
O
TIPSO
BOMO
H
O
OH
88
87
56%
O
TIPSO
BOMO
H
O
89
1) Im 2 CS, DMAP, CH 2 Cl 2
2) H 2 , [Ir(cod)py(PCy 3 ) 2 ]PF 6
94%
CH 2 Cl 2
H
Scheme 35 Intramolecular aldolisation in the synthesis of punctaporonin C
O
S O 2 Ph
O
Cl
O
O
PhO 2 S
LHMDS
(2 equiv)
LiBr
THF, rt
91
90
78%
O
Cl
O
Pterulone
Scheme 36 Access to the pterulone core structure by intramolecular substitution
300
O. Piva