Total Synthesis of Natural and Non-

O O
AcO AcO Natural Δ5,6 Δ12,13-Jatrophane
Diterpenes

BzO H O O H O
O O Christoph Schnabel, Katja Sterz, Henrik
Muller, Julia Rehbein, Michael Wiese and
O Martin Hiersemann
1b 1a J. Org. Chem. 2011, 76, 512–522
Technische Universita€t Dortmund,
Germany

Mohamad Nazari 6th, April 2011

Jatropha- 5,12-dienes, have been isolated from E. characias, E. pubescens, and E. elioscopia. In
addition to their fascinating structure, they are inhibitors of the P-glycoproteins.

In this article the authors present the total synthesis of the jatropha-5,12-diene 1a and 1b. The
key step of the synthesis of the cyclopentane fragment which is an uncatalyzed intramolecular
carbonyl-ene reaction.

Scheme 1. retrosynthesis of 1a and 1b

O O
HO HO
1a or 1b

HO H O TBSO H O
2 3

HO TBSO
CO2Me
OPMB

F3B
TBSO TBSO I O
6 5 4

Scheme 2. Synthesis of the Boronate 4

O I
1) LDA, - 78 C, B
CH2=CHCH2Br O O
O O
2) KOH, MeOH. H,O (84%) LDA, - 78 C
O
EtO B
3) MeLi (69%) O
7 8 9
1) KHF2
O 2) Bu4NOH
Bu4N F3B
70%
4
Scheme 3. Synthesis of Diol 15

O OH OH
9 steps (ref 1) CO2Me CO2Me
O NH

TBSO TBSO
10 11 12
(8.3 g) (5.3 g, 25%) (1.1 g, 5%)

1) LiAlH4 (90%)
2) Me2C(OMe)2, PPTS (85%)
3) O3, PPh3 (90%) 1) 9-BBN then A
4) CBr4, PPh3 (dppf)PdCl2, Ph3As, Cs2CO3
OH O O 86%
CO2Me 5) MeLi, MeI (78%)
6) Cp2Zr(H)Cl, I2 (80%) 2) H2O2 (68%)

TBSO TBSO I
12 13
SePh

OPMB A

OH OH O O
La(NO3)3.6H2O (54%)

TBSO OPMB TBSO OPMB

15 14

Scheme 4. Synthesi of Triene 17

H2C=C(Me)Li OH
OH OH OH O HO
IBX (75%) (91%)

TBSO OPMB TBSO OPMB TBSO OPMB

15 16 17
Scheme 5. Total Synthesis of 1a and 1b

OH 1) DDQ, DCM, pH 7 O
HO HO 1) B, toluene, 110 C, 2h
2) IBX, DCM, DMSO 2) HF.py
75%
54%
TBSO OPMB TBSO O

17 18
Mes N N
Mes
B Cl
Ru
Cl PCy Ph
3
O O
HO 1) p-Br-C6H4CO2H, PPh3, DIAD HO
2) K2CO3, MeOH

79%
H HO H O
HO O
19 2

1) EtCO2H, EDC.HCl, DMAP BzOH, PPh3, DIAD

2) Ac2O, TMSOTf (cat) 56% 87 %

O
O RO
AcO

BzO H O
O H O
Bz2O 20: R = H
O 1a TMSOTf 21: R = Bz (62%)
O (cat)
AcO
1) Ac2O, TMSOTf (cat)
2) m-CPBA, DCM, rt

H 69%
BzO O
O

References:
1) Schnabel, C.; Hiersemann, M. Org. Lett. 2009, 11, 2555–2558