The intramolecular coupling between a vinyl iodide and an allylic alcohol under
Jeffery’s conditions was advantageously applied to a 12-step total synthesis of
strychnine 94 by MacMillan et al. (Scheme 40) [60].
A few years ago, Lautens et al. have developed a straightforward synthesis of
benzoxepines by combining a Catellani-type palladium-catalysed aromatic substitution with an intramolecular Heck reaction to form 104 from 102 to 103
(Scheme 41) [61].
O
Br
O
O
96 (6-exo-trig, 39%)
97 (7-endo-trig, 61%)
Dioxane
110°C
Pd 2 (dba) 3
(2 mol %)
PCy 2
MeO
MeO
(S-Phos)
95
Scheme 38 Access to dibenzooxepins by an intramolecular Heck reaction
CHO
N
H
N
SiMe 3 OH
1) NaHMDS, NMP
2) CuBr.Me 2 S
0 to 65 °C
N
O
OH
H
H
N
H
H
93
N
O
H
H
N
H
O
CO 2 H
CO 2 H
, Ac 2 O
NaOAc, AcOH
Strychnine, 94
H
92
5-10%
60-80%
D
F
Scheme 37 Brook rearrangement and Michael addition for the simultaneous formation of the D
and F rings of strychnine
H
O
OH
CO 2 Me
Pd(OAc) 2
tri-o-Tolylphosphine
HCO 2 H, Piperidine
MeCN
99
O
CO 2 Me
Br O
98
47%
Olopatadine. HCl
O
CO 2 H
N
Me
Me
H
Cl
Scheme 39 Application of an intramolecular Heck reaction to the synthesis of olopatadine
Synthesis of Seven-Membered Ring Ethers and Lactones
301