COMMUNICATION
NaHCO3. We postulated the net reaction (Scheme 2) to be
catalytic in the presence of an amine 2, possibly proceeding
via an iminium intermediate. In a similar fashion, the reac-
tion of a catalytic quantity of a sulfonamide 3 may be ex-
pected to produce the N-sulfonyl imine intermediate allow-
ing a similar catalytic olefination process. Herein, we de-
scribe the first examples of weakly basic amine- and sulfona-
mide-catalyzed Wittig olefination reactions.
proline (Table 1, entry 6) drove the reaction to completion
under the same conditions. Other amines such as morpho-
line and ephedrine were also effective in catalyzing the ole-
fination. We considered it necessary to focus on weakly
basic amines in order to differentiate possible iminium-cata-
lyzed process from base-mediated background processes. To
this effect, the reaction was found to be effectively catalyzed
by using N-methylaniline (pKa =4.56 (BH+)) under the
standard conditions (Table 1, entry 7), whereas the use of
the tertiary amine N,N-dimethylaniline (pKa =2.45 (BH+))[9]
resulted in only background olefination (Table 1, entry 8).
This reaction (Table 1, entry 7) was efficiently catalyzed
with only 2 mol% of N-methylaniline.
Model and control reactions involving the synthesis of 4-
chlorostilbene (5a) were initially investigated with the
triethyl- and triphenylbenzyl phosphonium salts 4a and 4b,
(Table 1). A protocol involving the reaction of the aldehyde
(1.00 equiv), phosphonium salt 4a or 4b (1.00 equiv) at a
concentration of 2.0 molLÀ1 in water with
a
catalytic
The success of N-methylaniline in catalyzing the olefina-
tion encouraged us to pursue even weaker bases. Diphenyla-
mine (pKa =0.78 (BH+)) also proved highly effective in pro-
moting the reaction (Table 1, entry 9) at low catalyst load-
ing, as did a catalytic amount of the very weakly basic p-tol-
uenesulfonamide (Table 1, entry 10). Under the standard
conditions reported in Table 1, the use of 2 mol% tosyla-
mide promoted the reaction to full conversion within 6 h at
508C. This reaction completes a circle and connects the pos-
sible iminum-ion-mediated pathway as a catalytic variant of
the stoichiometric N-sulfonyl-imine-mediated olefination de-
scribed by Tian et al.[6] The E/Z olefination stereochemistry
observed here is fully in accord with expected results with
semi-stabilized ylides derived from triethyl-[4] and triphenyl-
phosphane under thermodynamic aqueous conditions.[3]
The new amine- and sulfonamide-catalyzed olefination
processes were successfully extended toward the synthesis of
a small panel of trans-stilbenes by using the triethylphospho-
nium salt 4a in the presence of either a catalytic amount of
morpholine, N-methylaniline (Table 2), or tosylamide
(Table 3). Although salt 4a reacts slower than 4b as indicat-
ed above (Table 1), this reaction provides high E-selective
olefins and full conversion is attained within 72 h. A range
of both electron-poor and electron-rich aldehydes was
shown to undergo olefination successfully. Under the condi-
tions shown in Tables 2 and 3, a control experiment (ab-
sence of any added amine) indicated only 5% background
stilbene (Table 2, entry 1). Using 10 mol% of morpholine as
catalyst yields a range of trans-stilbenes with high E-selectiv-
ity (Table 2, entries 2–8). The choice of morpholine as cata-
lyst was not critical and indeed, the present reaction was
also highly successful when catalyzed by either N-methylani-
line (Table 2, entries 9 and 10) or tosylamide (Table 3).
We further extended the applicability of the organocata-
lytic Wittig reaction to include the generation and trapping
of stabilized ylides derived from the (ethoxycarbonylme-
thyl)triisobutylphosphonium bromide 4c. Employing either
l-proline or tosylamide as catalyst (10 mol%), the olefina-
tion occurred smoothly under our standard aminocatalysis
conditions with electron-rich and electron-deficient alde-
hydes yielding the substituted cinnamate esters 7a–7c in
high yield and with exclusive E stereoselectivity (Table 4).
The mechanism(s) involved in the weakly basic amine-
and sulfonamide-catalyzed Wittig processes described above
amount of amine (2–20 mol%) and NaHCO3 (1.00 equiv) at
508C (1008C in the case of entries 3 and 4, Table 1) was
used. Under these conditions, no reaction occurred with salt
4a in the absence of any added amine at 508C (Table 1,
entry 1). Addition of l-proline caused the reaction to pro-
ceed slowly (Table 1, entry 2). This olefination reaction went
to completion at 1008C over three days to give the stilbene
in quantitative yield (Table 1, entry 4). A control experiment
showed that only 4% olefin conversion occurred over three
days at 1008C (Table 1, entry 3) in the absence of l-proline.
Reaction with the triphenyl salt 4b proved to be much
faster than 4a. Control experiments demonstrated 13%
background olefination (Table 1, entry 5) under the standard
condition (508C, 6 h) without amine, however addition of l-
Table 1. Various amine catalysts in the synthesis of 4-chlorostilbene (5a)
through the aqueous Wittig reaction.
Entry Amine
(loading)
Phosphonium salt Conversion Stilbene 5a
G
[%]
E/Z
1
2
3
4
5
6
none
none
none
4a
4a
4a
4a
4b
4b
0
–
35
4
84:16
–
>99
13
84:16
45:55
43:57
>99
7
8
4b
4b
>99
50:50
44:56
15
9
4b
4b
99
99
50:50
46:54
10
Chem. Eur. J. 2011, 17, 8794 – 8798
ꢀ 2011 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
8795