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

1.3 – Nucleophilic dearomatisation
1.3.3.b Asymmetric catalysis
Tomioka and co-workers found that bulky alkyl imines 72 reduce direct addition and
preferentially react in a conjugative manner. This process becomes asymmetric in the
presence of chiral diether 73.
Ph
c-Hex
Ph
N
OMe
i) NuLi, OMe 73
ii) H 3 O +
CHO
Nu
NaBH 4
HO
Nu
72
74
Nu = n-Bu, 80%, 91% e.e.
= t-Bu, 79%, 59% e.e.
= Ph, 82%, 94% e.e.
= Me, 19%, 64% e.e.
Scheme 1.19 – asymmetric addition of organolithiums to naphthylimines 46
Whilst the reaction is catalytic in diether 73, stoichiometric amounts are required,
proposed to be due to the azaenolate intermediate competing as a ligand for the
organolithium, reducing the amount of unbound catalyst in solution. Since enolates
are less basic, this work was extended to look at the catalytic asymmetric addition to
BHA ester 75 (Scheme 1.20). In racemic reactions BHA ester 75 was found to offer
the best regio- and diastereoselectivity of a number of ester 47 and a 20% loading of the
chiral ether was found to be optimal for asymmetric catalysis. Only a small sample of
nucleophiles is reported, and both yields and enantiomeric purities are modest.
O
OBHA
i) NuLi, 73 (20 mol%)
Toluene, −45 °C
HO
Nu
75
ii) LiEt 3 BH
iii) MeOH
iv) NaBH 4
74
Nu = 1-Naphthyl, 75%, 67% e.e.
= Ph, 76%, 75% e.e.
= n-Bu, − %, 21% e.e.
Scheme 1.20 – asymmetric addition of organolithiums to naphthylcarboxylates 48
40