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

Chapter 2 – Dearomatising additions to aryl oxazolines
Ph
Ph
Ph
Me
Ph
Ph
Me Ph
Ph
Ph
O
N
i) Me 3 SiCH 2 Li (3 eq)
THF, DMPU (6 eq)
O
N
O
N
O
N
Me
ii) MeI
SiMe 3
OMe
101b
OMe 20% OMe 2% OMe 1%
117 118 102b"
Scheme 2.9 – addition of (trimethylsilyl)methyllithium
A similar by-product was observed by Cabedo when treating the unsubstituted
aromatic oxazoline with tert-butyllithium. In the absence of both regioisomers, 119
was initially assigned with a methyl at C5, in light of the above result it has been
reassigned as shown.
Ph
Ph
Ph
Ph
Ph Me
Ph
O
N
i) t-BuLi (1.5 eq)
THF, DMPU (6 eq)
O
N
Me
O
N
ii) MeI
17%
17%
101a
102a"'
119
Scheme 2.10 – addition of tert-butyllithium
The modest diastereoselectivity for addition of s-BuLi is likely to be the result of the
kinetic resolution of the organolithium whose stereogenic centre can rapidly invert. A
similar level of diastereoselectivity was observed for the addition to para-anisole
101b.
Ox*
i) s-BuLi (3 eq)
THF, DMPU (6 eq)
Ox* Me
*
Ox*
OMe
101b
ii) MeI
OMe
102b'
71%
*d.r. 7:2
OMe
116b'
7%
Scheme 2.11 – addition of sec-butyllithium to oxazoline 101b
Perhaps the most surprising outcome of these reactions is the specificity for secondary
nucleophiles, in stark contrast with the dearomatising additions of Meyers, which
worked with a vast range of alkyllithiums. The nucleophilicity of organolithiums
65