hirsutene LECTURE NINE
N
gareth j rowlands
©Axpd@en.wikipedia

H
H H
hirsutene
J. Am. Chem. Soc., 1985, 107, 1448 &
Tetrahedron, 1985, 41, 3943
©AJC1@flickr

O Bu3SnH,
AIBN O
40%
I O
O H
Org. Biomol. Chem., 2007, 5, 1776
multiple-bond for
ming steps ©tallkev@flickr

O Bu3SnH, O
AIBN O
40%
I
O O O
O
O O
O
H O O
multiple-bond for
ming steps ©tallkev@flickr

✓
radicals
neutral conditions
functional group tolerance
rarely solvated (small)
highly reactive

✗
radicals
unselective(?)
unpredictable
highly reactive
misunderstood

3
radical
reactions
O Bu3SnH
AIBN
R 1 R 2 heat O
Br 1 2
R R

1. initiation
N CN 2x
NC N
NC
N N
H SnBu3 SnBu3
NC NC H

1. initiation
N CN 2x
NC N
NC
N N
H SnBu3 SnBu3
NC NC H

2. propagation
Bu3Sn Br Bu3Sn Br
O O
R1 R2 R1 R2
O
O
H SnBu3 SnBu3
R1 R2
R1 R2
H

2. propagation
Bu3Sn Br Bu3Sn Br
O O
R1 R2 R1 R2
O
O
H SnBu3 SnBu3
R1 R2
R1 R2
H

2. propagation
Bu3Sn Br Bu3Sn Br
O O
R1 R2 R1 R2
O
O
H SnBu3 SnBu3
R1 R2
R1 R2
H
chain carrier

3. termination
O
O
R1 R2
R1 R2
SnBu3 SnBu3

©gonzales2010@flickr
problem
tin is
another lecture
toxic course

of
retrosynthesis
hirsutene
5-exo-dig radical
H cyclisation H
H H H H
5-exo-trig radical
cyclisation
I
H
H H H H H H
radical cascade

simplificatio
n

of
retrosynthesis hirsutene
C–C bond
I formation I
I
H H H H
FGI
PGO I
O FGI O
OH OH
H H H H

of
retrosynthesis hirsutene
C–C bond
I formation I
I
H H H H
FGI
PGO I
O FGI O
OH OH
H H H H

of
retrosynthesis hirsutene
C–C bond
I formation I
I
H H H H
FGI
PGO I
O FGI O
OH OH
H H H H

of
retrosynthesis
hirsutene
C–C bond
PGO formation PGO O
O
OH
OH
H
H H

of
retrosynthesis
hirsutene
O SN2 O
OH OH
≡
X
H H

of
retrosynthesis
hirsutene
O SN' O O
OH
≡
H H

the
synthes
is
©deqalb@flickr

O
O 1. NaBH4, CeCl3
2. Ac2O, Et3N O
LDA
tBuMe2SiCl
OTBS
of
synthesis O
hirsutene

Luche
reduction
H H H
H H B H
B CeLn
O
H CeLn H
δ+
O
tethered hardness

how would you
achieve
enantioselectivity? ©youngrobv (Rob & Ale)@flickr

Ireland -Claisen
rearrangement
OTBS
CHCl3
reflux O
O
OTBS
H

O O
H H
Δ H H
TBSO TBSO
≡
H
H O
Ireland -Claisen OTBS
rearrangement

of
synthesis
bicyclic lactone
1. PhSeCl
O 2. H2O2 O
O
OTBS 62% from
H acetate H

Ph
H
Se H
O
O
OTBS
OTBS
PhSe
lactonisation O
O
H

Ph
PhSe O Se
O
O
O H
O
H
H
H
O
elimination O
H

of
synthesis hirsutene
O O Br
Li naphthalenide
then OTHP
CuBr•SMe2
CO2H
O 50-75% H
O
H
H

of
synthesis hirsutene
HO
OTHP 1. PPTS
2. LiAlH4 OH
CO2H
H 64%
H H H
1. (CF3SO2)2O, pyr
2. n-Bu4NI
64%
I I
1. nuc
2. CsF I
78%
H H H H
Me3Si Li

radical cascade
I
n-Bu3SnH, AIBN 5-exo-trig H
PhH, reflux cyclisation
80%
H H H H H H
5-exo-dig
cyclisation
H
Bu3Sn H H
H
H H
H H

of
power
radical
cascades ©ǝoɾoqɹnʇ@flickr