Chemistry Reference
In-Depth Information
Me
3
Si
HO
OMe
2.232
OMOM
OMe
O
2.234
1.
HB
1. DIBAL
2. NIS
O
2. H
2
O
I
OMe
HO
B(OH)
2
2.233
Me
3
Si
OMOM
OMe
2.235
(Ph
3
P)
4
Pd
TlOH
OMe
HO
Me
3
Si
OMOM
OMe
2.236
Scheme 2.80
O
1.
HB
O
CO
2
Et
TBSO
TBSO
2.
I CO
2
Et
(Ph
3
P)
4
Pd, NaOH
TBSO
TBSO
2.237
2.238
Scheme 2.81
A Suzuki coupling was the key step in a synthesis of the iconic molecule, quinine
2.244
, serving to connect
the two halves of the molecule together (Scheme 2.82).
88
The vinyl boronate
2.240
was prepared in an unusual
fashion, by a modified Takai reaction from the aldehyde
2.239
. Suzuki coupling with the bromoquinoline
2.241
was unsuccessful until SPhos
1.16
was employed as a catalyst. Stereoselective epoxidation of the
internal alkene of the Suzuki product
2.242
was then achieved indirectly using a Sharpless protocol
89
via
dihydroxylation. Deprotection of the nitrogen atom was achieved, again, in an unusual way, by treatment
with a strong Lewis acid. On heating, the quinuclidine core could then form by nucleophilic attack of the
now-free nitrogen on the near terminus of the epoxide
2.243
. The related natural product, quinidine
2.245
,
could also be synthesized by changing the reagent for dihydroxylation from ADmix-
to ADmix-
.
2.6.2 Alkyl Borane Coupling Reactions
The coupling of alkyl boranes with a wide variety of halides is a flexible route for carbon-carbon bond
formation. The borane partners are usually prepared using 9-BBN that is both highly selective for borylation
at the terminal position of an alkene, and highly selective for the less-hindered alkene (Scheme 2.83). The
coupling was used to form a
trans
alkene in a synthesis of brevicomin
2.253
(Scheme 2.84).
90
After coupling,
asymmetric dihydroxylation of the coupling product
2.251
and acetal exchange completed the synthesis.
