CHEM01200604012 Dibakar Goswami - Homi Bhabha National ...

IV.1.2: Previous syntheses
Given its biological importance, (R)-arundic acid has become an important target
for the organic chemists, and a large number of enantioselective syntheses are reported in
literature. 144 Some of the interesting approaches are briefly discussed in the following.
The first procedure, using the optical resolution of racemic 2-hexyl-4-pentynoic
acid, 144a gave poor yields (27%) due to the need of five recrystallization cycles to get a
final enantiomeric purity of 90% ee. 144b Next published methods were based on the
asymmetric alkylation of chiral enolates. When L-prolinol was chosen as chiral
auxiliary, arundic acid was prepared in 20% overall yield after a single recrystallization
(96% ee). 144c Hasegawa et al., 144d,e using Oppolzer's camphorsultam, obtained the
acid 1 with >99% ee after two recrystallizations (59% overall yield), but the expensive
chiral auxiliary could not be recycled. In such an approach, 144d the amide 93 of Oppolzer's
camphorsultam was subjected to α-allylation to produce 94, which was converted to the
target compound V via hydrolysis and hydrogenation (Scheme IV.1.1).
NH
i
N
O
S
O S
2
S
O 2
92 93 94
O 2
C 7 H 15
N
O
C 6 H 13
iii, iv
V
(i) C 7 H 13 COCl, Et 3 N, DMAP, THF, 0 o C; (ii) LDA, THF, CH 2 =CHCH 2 Br, LiI/DMI, -78
o C; (iii) Aqueous Bu 4 NOH, H 2 O 2 , 2-methyl-2-butene, DME, -10 o C; (iv) H 2 , Pt-C, i-PrOH,
25 o C.
139