Page 1207 - Advanced Organic Chemistry Part B - Reactions & Synthesis

Scheme 13.17. Juvabione Synthesis: E. Nagano and K. Mori a 1183
A SECTION 13.2
B
1) baker's yeast H C H Illustrative Syntheses
O, DMAP CO H O 1) LDA, CH I O
3
2) Ac 2 1) CH 3 3 O 2) DiBAIH OH
, CH Li 2) H +
3
3) TsNHNH 2
O O 4) pyridium dichromate (PDC) O H H CH 3
P = CH
1) Ph 3 2
2) KH
D
F 3) ICH 2 SnBu 3
E 4) BuLi
CH OH
CO 2 3 CH 2
CO CH 1) c -Hex BH, 1) CrO 3
2 3 2
–
H O , OH 2) CH N
2
CH 3 2) PCC 2 CH 2 H 2 2 H
H CH 3) NaOMe CH
O CH 3) (CH ) CHCH MgBr 3 3
2
3 2
CH 3 3
4) PCC
a. E. Nagano and K. Mori, Biosci. Biotechnol. Biochem., 56, 1589 (1992).
A final crucial step in this synthesis was an anionic [2,3]-sigmatropic rearrangement
of an allylic ether in Step D-4 to introduce the C(1) carbon.
H
O – OCH
LiCH 2 2 H
CH 2
CH 2
CH 3 CH 3
Another enantioselective synthesis, shown in Scheme 13.18, involves a early
kinetic resolution of the alcohol intermediate in Step B-2 by lipase PS. The stereo-
chemistry at the C(7) methyl group is controlled by the exo selectivity in the conjugate
addition (Step D-1).
Cu
CH 3
O O
CH
H 3

The bicyclic ring is then cleaved by a Baeyer-Villiger reaction in Step D-2. Another
interesting feature of this synthesis is the ring expansions used in sequences A and F.
Trimethylsilyl enol ethers were treated with Simmons-Smith reagent to form cyclo-
propyl silyl ethers. These undergo oxidative cleavage and ring expansion when treated
with FeCl and the -chloro ketones are then dehydrohalogenated by DBU. 22
3
. O O
+
OSi(CH ) OSi(CH ) O Si(CH )
3 3
3 3
3 3
FeCl 3
[Fe(II)Cl ] – Cl
3
FeCl 2
22
V. Ito, S. Fujii, and T. Saegusa, J. Org. Chem., 41, 2073 (1976).