30 A New Synthesis of Indoles
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M.
LE
CORRE,
A.
HERCOUET,
and
H.
LE
BARON
Laboratoire de Synthèse Organique, Université de Rennes I, Avenue du Général Leclerc, 35042 Rennes Cédex, France
Indoles were prepared (80-95%) from o-acylaminobenzyltriphenylphosphoranes by intramolecular Wittig reaction. Madelung synthesis of indoles1 is initiated only by strong bases at elevated temperatures. Prior deprotonation of the amide group greatly reduces the electrophilicity of the carbonyl group, and the useful scope of this synthesis is therefore limited to molecules which can survive very drastic conditions (scheme 1)
H S cheme 1
We now wish to report a new simple method for the synthesis of indoles which is based on the intramolecular reaction of amide with aIkylidenephosphoranes2(scheme 2) CH -PPh~X
CH-PPti
0
2
3
(gr 1
NR-CO-R I
3
X
^^ NR-C0-R» 2 Scheme 2
I
I
R
R
In a general procedure, 1,1 equivalent of base (CHONa, t-BuOk or t-AmONa) was added to a stirred suspension of 1 equivalent of dry phosphonium salt in boiling toluene. After being stirred for 10 min, the solution was filtered and evaporated to dryness. The crude material was essentially the desired indole with triphenylphosphine oxide. The yields for the reaction in scheme 2 are for isolated pure products obtained by preparative 3
0097-6156/81/0171-0153$05.00/0 © 1981 American Chemical Society
In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.
154
PHOSPHORUS
CHEMISTRY
Downloaded by UNIV OF CALIFORNIA SANTA CRUZ on October 14, 2014 | http://pubs.acs.org Publication Date: November 11, 1981 | doi: 10.1021/bk-1981-0171.ch030
l a y e r chromatography on s i l i c a g e l ( 1 : 1 ether-benzene) o r by c r y s t a l l i z a t i o n from ethanol. As shown i n Table I , t h e y i e l d s of s u b s t i t u t e d indoles,obtained through the use o f t h i s procedure were q u i t e good. Not only i s t h i s r e a c t i o n compatible w i t h a wide v a r i e t y of s u b s t i t u e n t s at the 2 p o s i t i o n , but our procedure can a l s o be used to prepare 1-substituted i n d o l e s .
R H
CH
H
96
3
-C(CH )-CH 3
H
C
yield(%)
R'
C
H
H
6 5 p-N0 -C H
H
P-CH 0-C H
2
6
3
CH
H
6 5
2
4
6
4
3
mp (°C) 61
^
93
118-120
97
189-190
93
249-251
85
228-230
80
liq.
l i t . _, m.p. 62°C ; (b) l i t 1, . m.p. 188-189°C ; (c) m. p. 251·-252°C ; (d) l i t . £, m.p. 230-230,5°C.
(b) (c) (d)
l i t6
~»
The o-acy1aminobenzylphosphonium s a l t s are a v a i l a b l e from two ways : ( 1) r e d u c t i o n o f
