A Route to Carbasugar Analogues - Jonathan Clayden - The ...

1.3 – Nucleophilic dearomatisation
1.3.2 Dearomatising additions to oxazolines
1.3.2.a Pyridyloxazolines
During the attempted ortho-lithiation of 3-pyridyl oxazoline 30, Meyers and coworkers
isolated dihydropyridine 31, the product of nucleophilic addition (Scheme
1.9).
E
N
O
N
i) RLi
X
ii) E +
O
N
i) RLi,
trace H 2 O
N
ii) E +
N
H
30 31
R
H
O
N
82-100%
R = Ph, Me, n-Bu, t-Bu
Scheme 1.9 – unexpected dearomatising addition to pyridine 22
Use of a chiral oxazoline 32 was found to impart good diastereoselectivity giving
carbamates 33 in high diastereomeric purity (Table 1.4). Nucleophilic addition was
also possible for Grignard nucleophiles (entries d, e).
N
O
N
Ph
OMe
i) Nu-M
ii) ClCO 2 Me
Nu
32 COOMe 33
N
O
N
Ph
entry Nu-M T / °C Yield / % d.r.
a MeLi –45 79 93 : 7
b MeLi –78 79 94 : 6
c n-BuLi –78 92 97 : 3
d MeMgCl 0 88 91 : 9
e n-BuMgCl 0 98 95 : 5
H
OMe
Table 1.4 – asymmetric dearomatising addition to pyridines 23
1.3.2.b Addition to achiral naphthyloxazolines
Meyers and co-workers later managed to extend this reaction to carbocycles in the
form of naphthalene 34 (Table 1.5). 24
Whilst the first reactions were discovered for
26