Merging organocatalysis with an indium(III)-mediated process: A stereoselective α-alkylation of aldehydes with allylic alcohols

Article abstract of DOI:10.1002/chem.201001693

Curiosity killed the CAT..ions! The use of stabilized cationic intermediates can be considered as a new frontier in the development of stereoselective reactions. An organocatalytic procedure mediated by the MacMillan imidazolidinone catalyst was coupled with an InBr_3-mediated process for the development of a novel stereoselective allylation reaction of aldehydes. Up to 98 % ee and up to 5:1 d.r. were obtained in the process.

Full text of DOI:10.1002/chem.201001693

COMMUNICATION
DOI: 10.1002/chem.201001693
Merging Organocatalysis with an IndiumACTHNUTRGNE(NUG III)-Mediated Process:
A Stereoselective a-Alkylation of Aldehydes with Allylic Alcohols
Montse Guiteras Capdevila,[a] Fides Benfatti,[a] Luca Zoli,[a] Marco Stenta,[b] and
Pier Giorgio Cozzi*[a]
Organocatalysis has grown explosively in the last few
years,[1] becoming an exciting area of research, and organo-
catalytic modes of activation are now considered in the syn-
thetic approach of complex natural products.[2] Activation
modes of organocatalysis allow new reactivity, increasing
the creativity of organic chemists towards the invention of
new reactions.[3] Recently, the combination of organocataly-
sis with metal catalytic processes produced exciting strat-
egies for the development of innovative transformations and
for challenging difficult problems.[4] In particular, Cordova
and Ibrahem disclosed the first example of the fusion be-
tween transition-metal catalysis and aminocatalysis for the
direct catalytic intermolecular a-allylic alkylation of alde-
hydes and cyclic ketones.[5] However, both his group and
that of Saicic[6] were unable to find conditions for perform-
ing allylation in an highly enantioselective fashion by the
use of an organocatalyst.[7]
and co-workers,[10] and InBr3 as a co-catalyst, avoiding the
employment of expensive Pd and Ir metals. Recently, we
have focused our attention on the development of a alkyla-
tion of aldehydes by SN1-type of reaction with alcohols.[11]
Our approach was to combine two powerful concepts, the
Mayrꢀs scales[12] of electrophilicity and nucleophilicity with
enamine catalysis.[13] We were able to use alcohols, such as
xanthol (I), capable of forming a relatively stable carbocat-
ion as electrophiles in the alkylation of aldehydes. The benz-
hydrilic carbocations generated in situ in our process were
positioned from À7 to À1 of the Mayrꢀs scale. Alcohols
leading to carbocations found to be above the mentioned
limits, such as 1,3-diphenyl-prop-2-en-1-ol (1) (1,3-diphenyl-
allyl alcohol), were completely un-reactive in our condi-
tions[14] and only the self condensation of aldehyde was ob-
1
served by H NMR spectroscopy in the crude reaction mix-
ture (Scheme 1).
Conversely, List and Mukherjee by using Brønsted acid
catalysis, reported the first enantioselective allylation of a-
branched aldehydes, combining the chiral phosphoric acid
(R)-TRIP with Pd0 catalysis.[8] Recently, enamine organoca-
talysis was exploited by Breit and co-workers in a dual Pd/
proline-catalyzed a-allylation of aldehydes with alcohols,
but no enantiomeric excess was recorded in the reaction.[9]
Herein, we disclose a conceptually new approach towards
the organocatalytic allylation of aldehydes with allylic alco-
hols, by the use of organocatalysts developed by MacMillan
Generation of allylic carbocations from the corresponding
alcohols and their reaction with aldehydes and ketones in
the presence of an organocatalyst can be considered an in-
[a] M. G. Capdevila, Dr. F. Benfatti, Dr. L. Zoli, Prof. P. G. Cozzi
Dipartmento di Chimica “G. Ciamician”,
Alma Mater Studiorum, Universitꢁ di Bologna
Via Selmi 2, 40126 Bologna (Italy)
Fax : (+39)051-2099456
E-mail: piergiorgio.cozzi@unibo.it
[b] Dr. M. Stenta
Laboratory for Biomolecular Modeling
Ecole Polytechnique Fꢂdꢂrale de Lausanne (EPFL)
1050 Lausanne (Switzerland)
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201001693.
Scheme 1. Stereoselective reaction of activated alcohol I with aldehyde
promoted by the catalyst 2.
Chem. Eur. J. 2010, 16, 11237 – 11241
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
11237

Table 1. Reaction of 1 with the catalysts 2–5 in different reaction condi-
tions.
teresting approach for enantioselective allylic alkylation, as
the transformation of the allylic alcohol in more reactive
species is not required, and the employment of transition
metals (Pd, Ir) is avoided. To promote the formation of the
allyl carbocation we began to consider the admission of dif-
ferent Lewis acids in catalytic amounts, choosing as model
reaction the addition of octanal to 1 (Scheme 2). In fact, the
Entry[a]
Catalyst
Temp [8C]
Time [h]
Solvent
ee [%][b,c]
[d]
[d]
[d]
[d]
1
2
3
4
5
6
7
8
2
2
2
2
2
2
3
4
5
5
5
5
5
rt
rt
rt
rt
rt
0
0
0
0
0
60
60
60
60
12
12
48
48
12
72
5
Toluene
tBuOMe
CH3CN
CH3NO2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
50
71
[d]
[d]
9[e]
10[f]
11[g]
12[h]
13[i]
82
80
80
80
80
0
0
0
72
5
[a] The reactions were performed at the indicate temperature with
1 equivalent of alcohol 1, 3 equivalents of octanal, in the presence of
20 mol% of catalyst. 20 mol% of InBr3 (0.33m solution in CH3CN) was
added to the reaction mixture containing the aldehyde, the alcohol 1 and
the catalyst. The reactions were run until completion, shown by TLC.
1
[b] For all the reactions the d.r., measured by H NMR spectroscopy and
HPLC analysis was 1:1. [c] Determined by chiral HPLC analysis. The syn
and anti diastereoisomers had the same enantiomeric excess. [d] No
1
traces of the desired product was detected by H NMR analysis and GC-
MS analysis of the crude reaction mixture. [e] Yield of purified product
was 71%. [f] 5 mol% of InBr3 was used for the reaction. [g] 40 mol% of
Scheme 2. Reaction of 1 with octanal in the presence of InBr3 with the
organocatalysts 2–5.
the catalyst 5 was used in the reaction. [h] 20 mol% of InACTHUNRGTNEUNG(OTf)3 added as
solid was used for the reaction. [i] 20 mol% of InBr3-BINOL complex
was used for the reaction.
direct substitution of allylic alcohols with many different nu-
cleophiles is easily promoted by the presence of Lewis or
Brønsted acids.[15] Unfortunately, in our model reaction,
Lewis acids such as Cu
N
ACHTUNGERTN(NUNG OTf)3,
Sc(OTf)3, La(OTf)3, and ZnACHTGNUTRENNUNG
A
U
mixture of products[16] or no reactions. Therefore, we fo-
cused our attention on indium salts for this chemistry.
Indium salts are able to mediate several organic transforma-
tions, in the presence of water,[17] and are not deactivated by
water even when present in large excess. Moreover, the dy-
namic exchange between indium and basic nucleophiles
allows Lewis acid catalysis in the presence of basic
amines.[18] Therefore the model reaction was studied in the
presence of indium salts, and we were pleased to achieve
positive results, as shown in Table 1(entries 5, 6, 9–13) in the
presence of the MacMillan catalysts 2 and 5. In the absence
of indium salts, no reaction occurred. Different indium salts
or indium complexes were tested in the reaction, and on the
basis of these results, InBr3 employed in 20 mol% was se-
lected as the co-catalyst. The reaction took place in CH2Cl2,
but other solvents were completely ineffective. Proline (3)
or proline-derived catalysts such as 4 were also ineffective in
promoting the reaction. Quite interestingly, the ee improved
when the free MacMillan catalyst 5 was used. A major
drawback in the reaction was the moderate ee and the poor
d.r. (1:1) obtained in the reaction of 1,3-diphenyl-prop-2-en-
1-ol (1) with different linear aldehydes.[19]
Scheme 3. Stereoselective reaction of alcohols 6–12 with aldehydes pro-
moted by catalyst 5.
erated[20] and nucleophiles were shown to attack the less hin-
dered position of the allylic cation.[21] Therefore, a series of
allyl substrates 6–12 were prepared by addition of lithium or
magnesium aryl compounds to b-phenylcinnamaldehyde
(see Supporting Information for details).
We were delighted to verify that these more sterically hin-
dered allyl compounds gave improved selectivity in our re-
action, as confirmed by the data collected in Table 2.
Introduction of phenyl substituents in b-position increased
the d.r. in the reaction up to 2:1 in favor of the syn diaste-
reoisomer.
Since in the addition of aldehydes to benzhydrols the ster-
ical hindrance of the benzhydrilic carbocation is controlling
the d.r. of the reaction,[11] we planned to increase the hin-
drance of the carbocation generated in the presence of
InBr3 (Scheme 3). 1,1,3-Triphenylallyl cations are easily gen-
The reaction catalyzed by the MacMillan catalyst 5
(20 mol%) in combination with 20 mol% of InBr3 as the co-
catalyst showed a remarkable enantiocontrol in allylation of
aldehydes, with ee ranging from 85 to 98% obtained for the
major syn diasteroisomer. The reactivity of alcohols 6–12
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Stereoselective a-Alkylation of Aldehydes
COMMUNICATION
Table 2. Reaction of 6–12 with the aldehydes a–d, in the presence of cat-
alytic amounts of InBr3 and 5.
Entry[a]
Product
Yield [%][b]
d.r.[c]
ee [%] syn[d]
ee [%] anti[d]
1[e]
2[f]
3
6a
6a
6a
6a
6a
6b
6c
6d
7a
8a
8b
9a
—
—
—
87
90
88
90
—
72
75
72
77
[g]
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
2:1
4:1
4:1
2:1
2:1
3:1
5:1
5:1
11:1
20:1
4:1
70
4[h]
5[i]
6
traces
[g]
63
90
50
56
53
69
66
57
65
50
71
75
77
75
73
65
88
89
91
87
85
85
86
88
88
93
91
94
98
96
99
95
(2S,3R)
80
64
77
56
69
73
67
75
79
84
68
87
65
85
55
81
ACHTUNGTRNE(NUNG 2S,3S)
7
8
9
Figure 1. Stereochemical models for the stereoselective allylation of alde-
hydes.
10
11
12
13
14
15
16
17
18
19[e]
20[e]
21
ent as in the substrates 9, 11, and 12, the reaction became
more diastereoselective. In fact, with the substrate 11, a d.r.
of 5:1 was obtained. With the substrates 6–10, and 12 the
catalyst 2 was ineffective in promoting the reactions. As a
matter of fact, in the case of substrate 11 the reaction is pos-
sible even in the absence of InBr3, by the use of the catalyst
2, as the corresponding carbocation is more stabilized. In
this case, a d.r. up to 20:1 with the enantiomeric excess of
99% was obtained in the reaction.[24]
For gaining some knowledge about the role of the indium
salt in the reaction, the ethers 13 and 14 (Scheme 4) were
prepared by acid-catalyzed addition of methanol and Wil-
liamson etherification, respectively. The substrate 15 was ob-
tained as a 1:1 mixture of diastereoisomers by treating the
alcohol 1 with acids.
9b
10a
10b
11a
11b
11c
11b
11c
12b
[a] The reactions were performed at 08C with 1 equivalent of alcohol 6–
12, 3 equivalents of aldehyde, in the presence of 20 mol% of catalyst 5.
20 mol% of InBr3 (0.33m solution in CH3CN) was added to the reaction
mixture containing the aldehyde, the alcohol 6–12 and the catalyst.
[b] Yield after chromatographic purification. [c] The d.r. (syn vs. anti) was
measured by 1H NMR spectroscopy and HPLC analysis. The relative
configuration of syn and anti product 6b was established by chemical cor-
relation to known lactones (see text). The relative configuration of all
products was established by analogy (the CHO proton of major syn dia-
stereoisomer resonates at lower chemical shifts compared to the anti for
all products). [d] Determined by chiral HPLC analysis (see the Support-
ing Information for details). The absolute configuration of the product
6b was established by the TD-DFT calculation of the ECD spectra (see
text). The absolute configuration of all the other products was established
by analogy. [e] The reaction was performed in absence of InBr3 and in
the presence of the catalyst 2. [f] The reaction was performed at room
temperature (rt). [g] Not determined. [h] The reaction was performed at
À208C in DCM. [i] The reaction was performed at À208C in CHCl3.
Scheme 4. Reaction of the allyl ethers 13–15 with octanal, in the presence
of the catalyst 5, and InBr3.
was dependent on the stability of the corresponding allyl
cation.[22] Different aromatic and heteroaromatic groups
(Table 2, R=aryl, heteroaryl) were prepared and tested in
the optimal reaction conditions. With the substrate 6 (R=
Ph) good yields and selectivities (87–91% ee) were obtained
with different aldehydes (a--d) showing the generality of the
process. In all cases, irrespective of the aldehydes employed,
a d.r. ratio of 2:1 was recorded. Therefore, the sterical hin-
drance between the R group and the 1,1-diphenylethenyl
chain controls the simple stereoselection of the reaction. We
assume that the increased hindrance of the b-position en-
hances the steric interaction with the tert-butyl group of the
MacMillan catalyst in the transition state (Figure 1). When
the R group and the 1,1-diphenylethenyl chain have a simi-
lar sterical hindrance, the simple stereoselection registered
for the reaction was quite poor.[23] However, a better control
of the simple stereoselection can be realized with allylic sub-
strates in which the R aromatic group is differently substi-
tuted in the 2 and 6 positions. With an R group in which the
two substituents in position 2 and 6 of the aryl were differ-
The substrates 13–15 were tested in the reaction with oc-
tanal, in the presence of 20 mol% the MacMillan catalyst 5
and 20 mol% of InBr3 (Scheme 4). In all the three cases the
product 1a was isolated with same d.r. and ee (1:1 and
80%). On the other hand, when the reaction of 1 with octa-
nal in the presence of the MacMillan catalyst was stopped
after 20 min, 1 was completely consumed and the bis-allyl-
ether product 15, present as a 1:1 mixture of diastereoiso-
mers, was observed in the reaction mixture by 1H NMR
spectroscopy and TLC analysis. In a quite fast reaction the
catalytic amount of InBr3 promotes the formation of the al-
lylic ether by the reaction of the allylic alcohol 1 with the al-
lylic carbocation. The same behavior was generally observed
with the different allylic substrates 6–12 by checking the re-
action mixture by TLC. When the substrates 6–12 were
treated with a catalytic amount (20 mol%) of InBr3 in
CH2Cl2, a rapid red coloration of the solution was observed.
1H NMR spectroscopy of the crude reaction mixture showed
the formation of the corresponding ethers, obtained as a
mixture of diastereoisomers. Although the conversion of the
Chem. Eur. J. 2010, 16, 11237 – 11241
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
11239

P. G. Cozzi et al.
allylic starting alcohol is complete, the yields of the reac-
tions are moderate given the rapid formation of the dimeric
ether. The allylic carbocations are slowly generated in the
reaction mixture from the allylic ethers by the Lewis acid
activation with InBr3.[25] Apparently, just one molecule of
the MacMillan catalyst is involved in the stereo-determining
step.[26] The relative configurations of syn and anti products
were assigned by chemical transformation of the product 6b
to the corresponding lactones (Scheme 5). The aldehyde 6b
Experimental Section
To a solution of the compounds 6–12 (0.1 mmol, 1 equiv) in CH2Cl2
(1 mL) were added MacMillan catalyst 5 (0.02 mmol, 20 mol%) and al-
dehyde ( 0.3 mmol, 3 equiv) at 08C. The mixture was stirred for 5 min at
the same temperature and then a solution of InBr3 (20 mol%, 0.33m in
acetonitrile) was added slowly. The mixture was stirred until no further
conversion took place (monitored by TLC) at the same temperature.
Then the reaction was quenched with water. The organic layer was sepa-
rated, and the aqueous layer was extracted twice with Et2O. The com-
bined organic layer was washed with water, dried over Na2SO4, and con-
centrated. The residue was purified by flash chromatography (SiO2; cy-
clohexane: diethyl ether).
Acknowledgements
The European Commission through the project FP7-201431 (CATA-
FLU.OR), PRIN (Progetto Nazionale Stereoselezioni in Chimica Organi-
ca: Metodologie ed Applicazioni) and Bologna University are acknowl-
edged for financial support for this research.
Scheme 5. Reagents and conditions: a) NaClO2, H2O2 35%; CH3CN–
KH2PO4 buffer, 108C. b) TMSCHN2; Et2O, 0 8C. c) O3, MeOH. d)
NaBH4, MeOH, 42% (over four steps).
Keywords: aldehydes · allylic alcohols · indium · MacMillan
catalysts · organocatalysis
was oxidized to the acid,[27] which was esterified with trime-
thylsilyldiazomethane. The ozonolysis of the double bond[28]
followed by reduction with NaBH4 and lactonization gave
the lactones 16 and 17, separated by flash chromatography.
[1] For reviews, see: a) P. Melchiorre, M. Marigo, A. Carlone, G. Barto-
li, Angew. Chem. 2008, 120, 6232; Angew. Chem. Int. Ed. 2008, 47,
6138; b) C. F. Barbas III, Angew. Chem. 2008, 120, 44; Angew.
Chem. Int. Ed. 2008, 47, 42; c) S. Mukherjee, J. W. Yang, S. Hoff-
mann, B. List, Chem. Rev. 2007, 107, 5471; d) G. Lelais, D. W. C.
MacMillan, Aldrichimica Acta 2006, 39, 79. For recent overviews:
e) P. Melchiorre, Angew. Chem. 2009, 121, 1386; Angew. Chem. Int.
Ed. 2009, 48, 1360; f) D. W. C. MacMillan, Nature 2008, 455, 304.
[2] a) S. B. Jones, B. Simmons, D. W. C. MacMillan, J. Am. Chem. Soc.
2009, 131, 1336; b) J. Carpenter, A. B. Northrup, D. M. Chung,
J. J. M. Wieners, S.-G. Kim, D. W. C. MacMillan, Angew. Chem.
2008, 120, 3624; Angew. Chem. Int. Ed. 2008, 47, 3568; c) R. M.
Wilson, W. S. Jen, D. W. C. MacMillan, J. Am. Chem. Soc. 2005, 127,
11616.
[3] J. E. Wilson, A. D. Casarez, D. W. C. MacMillan, J. Am. Chem. Soc.
2009, 131, 11332.
[4] Z. Shao, H. Zhang, Chem. Soc. Rev. 2009, 38, 2745.
[5] I. Ibrahem, A. Cꢄrdova, Angew. Chem. 2006, 118, 1986; Angew.
Chem. Int. Ed. 2006, 45, 1952.
[6] F. Bihelovic, R. Matovic, B. Vulovic, R. N. Saicic, Org. Lett. 2007, 9,
5063.
3
The chemical shifts and the J coupling constant of the sepa-
rated products were compared to those reported in the liter-
ature for assigning the syn/anti relative configurations.[29]
The lactones 16 and 17 were also obtained by the same reac-
tion sequence performed on the product 1b. The absolute
configuration of the lactone derivatives was assigned on the
basis of the time-dependent density functional theory (TD-
DFT) calculation of the electronic circular dichroism (ECD)
spectra (see the Supporting Information for details).[30] The
S absolute configuration of the stereocenters in the a-posi-
tion was in complete agreement with our previous work
with stabilized carbocations,[11] and in general, with the dia-
stereofacial selection obtained with the MacMillan catalyst 5
in organocatalytic reactions.
[7] R. N. Saicic perfomed a stereoselective intramolecular allylation of
aldehydes in the presence of a BINAP–Pd catalyst.
In conclusion, we have described the first catalytic stereo-
selective addition of aldehydes to allylic alcohols promoted
by a combination of organocatalysis and a metal-catalyzed
process.[31] In this innovative transformation, a stereoselec-
tive reaction of stabilized carbocations is realized[13] by the
employment of a chiral nucleophile. The exploitation of
[8] S. Mukherjee, B. List, J. Am. Chem. Soc. 2007, 129, 11336.
[9] I. Usui, S. Schmidt, B. Breit, Org. Lett. 2009, 11, 1453.
[10] a) S. G. Ouellet, A. Walji, D. W. C. MacMillan, Acc. Chem. Res.
2007, 40, 1327; b) T. D. Beeson, A. Mastracchio, J. Hong, K. Ashton,
D. W. C. MacMillan, Science 2007, 316, 582; c) G. Lelais, D. W. C.
MacMillan, Aldrichimica Acta 2006, 39, 79. For a-allylic alkylation
of aldehydes by SOMO activation, see reference [10b].
À
such a strategy for the selective construction of C C bonds,
by the merger of organometallic and organocatalytic pro-
cesses is under further development in our laboratory.
[11] a) P. G. Cozzi, F. Benfatti, L. Zoli, Angew. Chem. 2009, 121, 1339;
Angew. Chem. Int. Ed. 2009, 48, 1313. For the generation of carbo-
À
cations by C H activation, see: b) F. Benfatti, M. Guiteras Capdevi-
la, L. Zoli, E. Benedetto, P. G. Cozzi, Chem. Commun. 2009, 5919.
[12] H. Mayr, B. Kempf, A. R. Ofial, Acc. Chem. Res. 2003, 36, 66, and
references therein.
[13] P. G. Cozzi, F. Benfatti, Angew. Chem. 2010, 122, 264; Angew.
Chem. Int. Ed. 2010, 49, 256.
11240
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Stereoselective a-Alkylation of Aldehydes
COMMUNICATION
[14] Water generated by the enamine catalysis is the nucleophile that is
competing with the enamine; for the nucleophilicity of solvents, see:
S. Minegishi, S. Kobayashi, H. Mayr, J. Am. Chem. Soc. 2004, 126,
5174.
[23] In fact, when 3,3-diphenyl-1-(2,4,6-trimethylphenyl)-prop-2-en-1-ol
(3-mesityl-1,1diphenylallyl alcohol) was allowed to react with octa-
nal, the corresponding product was obtained in 88% ee but in a d.r.
of 1:1.
[24] The carbocation derived from 11 is more stabilized then the carbo-
cation derived from 6. Replacement of the benzhydryl hydrogen in
benzhydrylium ions by a styryl group reduces the electrophilicity by
2 to 5 orders of magnitude For a discussion of stability of carboca-
tions in relation to the Mayr scale see references [11] and [12].
[25] K. Motokura, N. Nakagiri, T. Mizugaki, K. Ebitani, K. Kaneda, J.
Org. Chem. 2007, 72, 6006. See also reference [16a].
[26] A preliminary study of the “nonlinear effect” performed on the
model reaction with octanal and 1 gave a linear correlation among
the ee of the MacMillan catalyst 2 and the ee of the product 1a.
[27] E. Dalcanale, F. Montanari, J. Org. Chem. 1986, 51, 567.
[28] G. J. Dawson, J. M. J. Williams, S. J. Coote, Tetrahedron: Asymmetry
1995, 6, 2535.
[15] a) M. Yasuda, T. Somyo, A. Baba, Angew. Chem. 2006, 118, 807;
Angew. Chem. Int. Ed. 2006, 45, 793; b) M. Rueping, B. J. Nacht-
sheim, A. Kuenkel, Org. Lett. 2007, 9, 825; c) J. Kischel, K. Mertins,
D. Michalik, A. Zapf, M. Beller, Adv. Synth. Catal. 2007, 349, 865;
d) V. Terrasson, S. Marque, M. Georgy, J.-M. Campagne, D. Prim,
Adv. Synth. Catal. 2006, 348, 2063; e) K. Motokura, N. Fujita, K.
Mori, T. Mizugaki, K. Ebitani, K. Kaneda, Angew. Chem. 2006, 118,
2667; Angew. Chem. Int. Ed. 2006, 45, 2605; f) H. Qin, N. Yamagiwa,
S. Matsunaga, M. Shibasaki, Angew. Chem. 2007, 119, 413; Angew.
Chem. Int. Ed. 2007, 46, 409.
[16] For the reaction of 1,3-diphenyl allyl cation with nucleophiles, see:
a) R. Sanz, A. Martꢅnez, D. Miguel, J. M. Alvarez-Gutierrꢂz, F. Ro-
drꢅguez, Adv. Synth. Catal. 2006, 348, 1841; b) M. Noji, T. Ohno, K.
Fuji, N. Futaba, H. Tajima, K. Ishii, J. Org. Chem. 2003, 68, 9340.
[17] J. M. Huang, C.-M. Wong, F.-X. Xu, T.-P. Loh, Tetrahedron Lett.
2007, 48, 3375. For recent reviews, see: a) T.-P. Loh, G.-L. Chua,
Chem. Commun. 2006, 2739; b) C. G. Frost, J. P. Hartley, Mini-Rev.
Org. Chem. 2004, 1, 1.
[29] T. E. Lightburn, M. T. Dombrowski, K. L. Tan, J. Am. Chem. Soc.
2008, 130, 9210.
[30] a) G. Bringmann, T. Bruhn, K. Maksimenka, Y. Hemberger, Eur. J.
Org. Chem. 2009, 2717; b) P. J. Stephens, N. Harada, Chirality 2010,
22, 229; c) C. Diedrich, S. Grimme, J. Phys. Chem. A 2003, 107,
2524. For recent application of the technique in organocatalytic re-
actions, see: P. Galzerano, F. Pesciaioli, A. Mazzanti, G. Bartoli, P.
Melchiorre, Angew. Chem. 2009, 121, 8032; Angew. Chem. Int. Ed.
2009, 48, 7892.
[31] For a combination of gold and organocatalysis, see: S. Belot, K. A.
Vogt, C. Besnard, N. Krause, A. Alexakis, Angew. Chem. 2009, 121,
9085; Angew. Chem. Int. Ed. 2009, 48, 8923. For an overview, see:
A. S. K. Hashmi, C. Hubbert, Angew. Chem. 2010, 122, 1026;
Angew. Chem. Int. Ed. 2010, 49, 1010. During the preparation of
this manuscript, the enantioselective propargylation of aldehydes
using cooperative organocatalysis and transition-metal catalysis was
reported: M. Ikeda, Y. Miyake, Y. Nishibayashi, Angew. Chem.
2010; DOI: 10.1002/ange.201002591; Angew. Chem. Int. Ed. 2010;
DOI: 10.1002/anie.201002591.
[18] E. Mai, C. Schneider, Synlett 2007, 2136.
[19] Reaction of propanal to 1,3-diphenylpropan-1-ol in CH2Cl2 at 08C,
in the presence of 20 mol% of InBr3 afforded the corresponding
products in with a d.r. of 1:1 (syn: anti) in 85% yield and 73% ee
for both the stereoisomers. 5-Hexenal afforded, in the same reaction
conditions, a similar 1:1 diastereoisomeric ratio in 47% yield and
81% ee for both the stereoisomers.
[20] H. Mayr, C. Fitchner, A. R. Ofial, J. Chem. Soc. Perkin Trans. 2
2002, 1435. The carbocation derived from the compound 6 is posi-
tioned at E = +1.25 on the Mayr scale.
[21] A. C. Hopkinson, E. Lee-Ruff, T. W. Toone, P. G. Khazanie, L. H.
Dao, J. Chem. Soc. Perkin Trans. 2 1979, 1395.
[22] 4,4-Dimethyl-1,1-diphenyl-pent-1-en-3-ol and 1,4,4-triphenyl-but-3-
en-2-ol are completely unreactive substrates under the standard re-
action conditions.
Received: June 15, 2010
Published online: August 18, 2010
Chem. Eur. J. 2010, 16, 11237 – 11241
ꢃ 2010 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
11241