Chemistry Reference
In-Depth Information
TABLE 10.8. Diastereoselective Iodine(III)-Mediated Spirocyclization of O-Alkyl
Arylhydroxamates
R
2
R
2
R
1
R
3
R
3
R
1
PIFA
MeOH
O
N
MeO
O
NH
MeO
CH
2
Cl
2
-78 to -20°C
OMe
O
362
363
R
1
R
2
R
3
Entry
Yield (%)
dr (
anti
:
syn
)
1
H
Me
Me
75
>
98:2
2
Me
H
Me
75
5.6:1
3
H
n
-Bu
Me
79
>
98:2
4
n
-Bu
H
Me
87
5.3:1
5
H
Me
i
-Pr
81
>
98:2
6
Me
H
i
-Pr
72
6:1
7
H
Me
OMe
90
4:1
8
Me
H
OMe
85
12:1
9
H
n
-Bu
OMe
97
1.6:1
10
n
-Bu
H
OMe
68
11:1
11
CH
2
Ph
H
OMe
98
11:1
12
OTIPS
H
OMe
88
12:1
Unexpected findings of this methodological study include the surprisingly higher
degrees of 1,3-induction versus 1,2-induction (entries 7 and 8) for
o
-methoxy
substituents (entries 7-12) and decrease in stereoselectivity noted with increasing
steric bulk of the
-substituents (entries 7 and 9). Interestingly, this behavior is not
replicated for
o
-alkyl groups where the substitution of methyl (entry 2) for
n
-butyl
(entry 3) at the
b
b
-position did not have a deleterious effect upon diastereoselectivity.
10.7.2 Application of N-Acyl Nitrenium Ion Annulation to
Target-Directed Synthesis
Notwithstanding the extensive investigations of Glover, Kikugawa and others, to
date, application of the
N
-acyl nitrenium Ar
2
-n annulation reaction to the synthesis
of natural products and other complex targets has been relatively limited, despite its
apparent potential. In this regard, Kikugawa and co-workers were the first to employ
this chemistry in the preparation of a natural product,
140
namely eupolauramine
(
), an azaphenanthrene alkaloid isolated from the bark of
Eupomatia laurina
(Scheme 10.57).
141
Notably, this route features two, successive nitrenium-mediated
transformations: Zn(II)-promoted Ar
2
-6 annulation of
N
-chlorohydroxamate
368
364
proceeded exclusively at the
peri
position to yield
and establish the benzo[
h
]
quinoline skeleton, while acid-catalyzed methanolysis of this
N
-methoxy lactam
triggered a Bamberger rearrangement to introduce the C-6 methoxyl group.
142
From
365
