Direct vinylogous aldol reaction triggered by tetrabutylammonium fluoride: A highly regioselective and diastereoselective addition of cyclic β-haloenals to aromatic aldehydes

Article abstract of DOI:10.1055/s-0031-1290313

A new type of direct vinylogous aldol addition between cyclic β-haloenals and aromatic aldehydes promoted by TBAF has been developed. The reaction was carried out under mild conditions to provide highly functionalized δ-hydroxy-β-halo-α,β-unsaturated aldehydes with high diastereomeric ratios and low to good yields. Georg Thieme Verlag Stuttgart · New York.

Full text of DOI:10.1055/s-0031-1290313

468
LETTER
Direct Vinylogous Aldol Reaction Triggered by Tetrabutylammonium
Fluoride: A Highly Regioselective and Diastereoselective Addition of Cyclic
b-Haloenals to Aromatic Aldehydes
A
ddition o
i
f
Cyc
l
n
b
-Haloena
g
ls to Aromat
l
ic
A
lde
i
hydes Zhang, Lianghu Gu, Yuefa Gong*
School of Chemistry and Chemical Engineering, Huazhong University of Science and Technology,
1037 Luoyu Road, Wuhan 430074, P. R. of China
Fax +86(27)87543632; E-mail: gongyf@mail.hust.edu.cn
Received 1 November 2011
or alkynylenolates,7 and another involving heterocyclic
Abstract: A new type of direct vinylogous aldol addition between
cyclic b-haloenals and aromatic aldehydes promoted by TBAF has
been developed. The reaction was carried out under mild conditions
to provide highly functionalized d-hydroxy-b-halo-a,b-unsaturated
aldehydes with high diastereomeric ratios and low to good yields.
magnesium dienolates.8
Indeed, examples of direct VA reactions are rare despite
their distinct advantages of being more atom-economical
and ecologically friendly. Especially, converting an a,b-
unsaturated aldehyde into a dienolate, which served as nu-
cleophile in the direct VA addition, has still remained un-
explored. Three direct VA reactions of salicylaldehydes
with g-enolizable a,b-unsaturated aldehydes have been
reported by Woggon groups and Bräse groups.9 Addition-
ally, two preceding direct VA reactions involving Yama-
moto’s remote aldolization technique of a,b-unsaturated
aldehyde based on bulky aluminum tris(2,6-diphenylphen-
oxide) (ATPH) were also studied, which gave a variety of
functionalized d-hydroxy-a,b-unsaturated aldehydes.10
However, this direct VA reaction required the use of a
strong base, such as LDA, and operated at low tempera-
ture (–78 °C). Recently, we reported a more simple pro-
tocol that starts from a cyclic b-haloenal in the presence of
tetrabutylammonium fluoride (TBAF) to generate a cyclic
dienolate I in situ under mild conditions (Scheme 1).11
Key words: direct vinylogous aldol reaction, TBAF, cyclic b-ha-
loenals, regio- and diastereoselectivity, homoallylic alcohols
Vinylogous aldol (VA) reactions of dienolates have been
intensively investigated due to their application in the syn-
thesis of natural products and biologically active com-
pounds.1,2 Generally, a g-enolizable a,b-unsaturated
carbonyl compound can be used as a precursor of nucleo-
philic dienolate equivalent in a VA addition to give d-hy-
droxy-a,b-unsaturated carbonyl compounds in which up
to two stereocenters and one double bond can be created
simultaneously.1b
However, the VA reaction offers the challenges of site se-
lectivity and the already present issues of stereoselectivi-
ty. It has been a particular field of research for synthetic
chemists. Addition of a dienolate to an aldehyde has the
possibility to afford a mixture of both a- and g-addition
products. A common method that allows for g-site selec-
tivity is the use of preformed, stable dienolate equivalents,
which have been successfully applied to vinylogous
Mukaiyama aldol (VMA) reactions.3 Alternatively, the di-
rect VA reaction was performed on the unmodified g-eno-
lizable a,b-unsaturated carbonyl compounds by strong-
base-induced generation of the dienolates in situ, which
provides a practical entry to highly functionalized d-hy-
droxy carbonyl compounds and avoids the stoichiometric
preactivation of the vinylogous nucleophilic components.
For example, both direct VA4 and asymmetric direct VA5
additions between furanone or pyrrolinone systems and
carbonyl compounds to construct butenolide-related mo-
lecular fragments have been thoroughly studied in recent
years. A direct vinylogous nitroaldol reaction using ni-
troisoxazole was also reported by Adamo.6 In addition,
three cases in the acyclic direct VA reactions are worth
mentioning: two pertaining to the use of allenyl enolates
O–
α
CHO
X
CHO
X
deprotonation
base, r.t.
n
n
n
X
γ
n = 0, 1
X = Cl, Br
I
Scheme 1 A cyclic dienolate generated in situ
By converting an unsaturated aldehyde into a dienolate,
this reactive nucleophile I which present several possible
sites encouraged us to explore the aldol addition of an un-
saturated aldehyde to an aldehyde triggered by Lewis/
Brønsted bases at room temperature. Two possible path-
ways for the aldol addition are depicted in Scheme 2, we
wondered whether bases could solve the challenge of a di-
rect vinylogous nucleophilic addition of unmodified un-
saturated aldehydes.
We initiated our investigation of cyclic b-chloro enal 1a
(0.50 mmol) with an activated aldehyde 2a (0.65 mmol) in
the presence of TBAF (100 mol%) in THF at 25 °C. Inter-
estingly, the reaction mixture was stirred for 22 minutes to
give, after chromatography on silica gel, homoallylic al-
SYNLETT 2012, 23, 468–472
Advanced online publication: 19.01.2012
DOI: 10.1055/s-0031-1290313; Art ID: W61611ST
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x.
2
0
1
1

LETTER
Addition of Cyclic b-Haloenals to Aromatic Aldehydes
469
achieved. Use of DMSO as the solvent caused a signifi-
cant increase in the reaction rate and maintained a high
level of diastereoselectivity. Acetonitrile compromised
the yield and markedly retarded the reaction while exhib-
iting the highest diastereomeric ratio (99:1). Gratifyingly,
lowering the reaction temperature from 25 °C to 18 °C
caused an increase in the product yield to 69% after 1.5
minutes (Table 1, entry 5). Upon decreasing the amount
of TBAF to 90 mol% at 18 °C, the VA product was ob-
tained in excellent yield with 98:2 dr (Table 1, entry 6).
When 80 mol% or 50 mol% of TBAF were used instead
at 18 °C, the yield of 3aa fell to 78% and 67%, respective-
ly (Table 1, entries 7 and 8).
HO
X
R
α-addition
CHO
n
base, r.t.
CHO
+
R
CHO
OH
X
n
γ-addition
X
CHO
base, r.t.
R
n = 0, 1
X = Cl, Br
n
Scheme 2 Two possible pathways for the aldol reaction
Cl
OH Cl
CHO
Cl
CHO
CHO
Table 1 Optimization of Reaction Conditions for the Direct Viny-
logous Aldol Reactiona
Cl
1a
syn-3aa
TBAF
THF
+
+
Entry Base
(mol%)
Solvent Temp Timeb
(°C)
Yield dr
Cl
OH
(%)c (syn/anti)d
Cl
CHO
1
2
3
4
5
6
7
8
TBAF(100)
TBAF(100)
TBAF(100)
TBAF(100)
TBAF(100)
TBAF (90)
TBAF (80)
TBAF (50)
THF
r.t.
r.t.
22 min 57
97:3
98:2
98:2
99:1
98:2
98:2
98:2
98:2
Cl
Cl
2a
Cl
DMF
10 min 57
1 min 59
anti-3aa
DMSO r.t.
MeCN r.t.
Scheme 3 Direct vinylogous aldol addition triggered by TBAF
24 h
44
cohol 3aa in 57% yield with 97:3 dr detected by 1H NMR
spectroscopy (Scheme 3).
DMSO 18
DMSO 18
DMSO 18
DMSO 18
1.5 min 69
3 min 86
5 min 78
It is to be noted that the aldol addition occurred exclusive-
ly at the g-position of b-chloro enal 1a. The X-ray crystal
structure of homoallylic alcohol syn-3aa is shown in
Figure 1.12
3.5 h
67
a Unless otherwise noted, the reaction was carried out with 1a (0.5
mmol), aldehyde 2a (0.65 mmol), and base in solvent (3.0 mL) at r.t.
(25 °C) or 18 °C.
b Reaction was followed by TLC.
c Isolated yields.
d Determined by 1H NMR analysis.
Furthermore, we also examined the effect of TMAH,
TMAF, and KF on this VA reaction (Table 2). When 30–
60 mol% of TMAH (Table 2, entries 1–3) and 50–90
mol% of TMAF (Table 2, entries 4–6) were used instead
of TBAF, the reactions proceeded smoothly to give the g-
coupled aldol product 3aa in moderate yields with a high
level of diastereoselectivity. However, the transformation
in KF was not achieved due to the low concentration of
fluoride ion in DMSO (Table 2, entry 7).
Figure 1 X-ray crystal structure of homoallylic alcohol syn-3aa
Next, we optimized the reaction conditions for this direct
VA addition of the two different aldehydes 1a and 2a
(Table 1). Firstly, the reaction was carried out by employ-
ing different bases to study the effect of basicity on the
VA addition. To our disappointment, six organic amine
bases (DBU, DABCO, Et3N, DMAP, imidazole, and qui-
nidine) could not promote the above-mentioned VA reac-
tion at all. This result indicated that TBAF is an effective
base in the deprotonation of cyclic b-halo enal 1a to give
These investigations showed that only the basicity of the
fluoride ion or the hydroxide ion is strong enough to ab-
stract a g-proton directly from b-halo enal 1a under mild
conditions. The exocyclic dienolate II produced in situ re-
acts with an aldehyde at its g-site to afford intermediate
III. Subsequent protonation of III gives the VA product 3
(Scheme 4).
the enolate I in situ. Four different solvents listed in Based on these important examinations and a plausible re-
Table 1 were then tested (Table 1, entries 1–4). Conduct- action pathway as shown above, we selected the polar
ing the reaction in DMF gave the same yield as in THF, aprotic solvent DMSO and 90 mol% of TBAF at 18 °C as
and a slightly improved diastereomeric ratio (98:2) was the optimal reaction conditions to explore the substrate
© Thieme Stuttgart · New York
Synlett 2012, 23, 468–472

470
J. Zhang et al.
LETTER
scope for this direct VA reaction. Various aromatic alde-
hydes and the effects of ring substitution on the product
composition and diastereomeric ratio were assessed, low
to good yields and high diastereoselectivities were ob-
served for the VA product (Table 3). Substrates with elec-
tron-withdrawing groups exhibited much higher reactivity
than those with electron-donating groups. Using benzal-
dehyde 2b as the electrophilic reagent, the aldol reaction
proceeded at a higher temperature, and the corresponding
product 3ab was obtained in a lower yield than the elec-
tron-deficient aldehyde 2a. Unfortunately, the dehydra-
tion product 4ab was also found to form along with the
aldol product (Table 3, entry 1). Moreover, the position of
the substituents on the aromatic ring had an obvious effect
on the product composition and diastereoselectivity. The
reactions with electron-deficient aldehydes 2c–i exclu-
sively afforded aldol products in modest to good yields
with high diastereoselectivities (Table 3, entries 2–8). For
para- and meta-substituted benzaldehydes, the syn/anti
ratio was similar to that surveyed in benzaldehyde at
88:12 while the syn/anti ratio was notably enhanced by
ortho substituents on the aromatic ring. For a more steri-
Table 2 The effect of TMAH, TMAF, and KF on Reaction Yield
and Selectivitya
Entry Base
(mol%)
Solvent Temp Timeb
(°C)
Yield dr
(%)c (syn/anti)d
1
2
3
4
5
6
7
TMAH (30)
TMAH (45)
TMAH (60)
TMAF (50)
TMAF (70)
TMAF (90)
KF (100)
DMSO 18
DMSO 18
DMSO 18
DMSO 18
DMSO 18
DMSO 18
DMSO r.t.
15 min 47
1 min 58
10 s 31
97:3
97:3
97:3
98:2
98:2
98:2
–
40 min 45
1 min 61
20 s
48 h
52
–
a Unless otherwise noted, the reaction was carried out with 1a (0.5
mmol), aldehyde 2a (0.65 mmol), and base in solvent (3.0 mL) at r.t.
(25 °C) or 18 °C.
b Reaction was followed by TLC.
c Isolated yields.
d Determined by 1H NMR analysis.
Table 3 Direct Vinylogous Aldol Reaction of Cyclic b-Chloro Enal 1a with Various Aromatic Aldehydesa
OH Cl
CHO
CHO
R
Cl
1a
+
3
TBAF
+
DMSO, 18 °C
Cl
O
CHO
R
R
H
2
4
Entry
1
R
Time
6 h
Yield (%)b
Product ratio of 3/4c
3ab/4ab 83:17
3ac/4ac 100:0
3ad/4ad 100:0
3ae/4ae 100:0
3af/4af 100:0
3ag/4ag 100:0
3ah/4ah 100:0
3ai/4ai 100:0
3aj/4aj 68:32
3ak/4ak 73:27
3al/4al 97:3
dr (syn/anti)c
88:12
97:3
2bd Ph
30
81
81
68
53
50
47
41
20
26
55
–
2
2c 2-ClC6H4
2d 2-BrC6H4
2e 2-O2NC6H4
2f 3-O2NC6H4
2g 4-O2NC6H4
2h 4-MeO2SC6H4
2i 4-ClC6H4
3 min
3 min
3 min
3 min
2 min
5 min
22 min
6 h
3
98:2
4
98:2
5
85:15
87:13
90:10
87:13
83:17
97:3
6
7
8
9
2je 4-FC6H4
10
11
12
2kd 2-naphthyl
2l 2-furyl
6 h
30 min
12 h
80:20
–
2m 3,4-(MeO)2C6H3
–
a Unless otherwise noted, reactions were performed on a 0.50 mmol scale of 1a using 0.65 mmol of 2 and 90 mol% TBAF in 3.0 mL DMSO.
b Yields of isolated product.
c Determined by 1H NMR analysis.
d Reaction performed at 28 °C.
e Reaction performed at 32 °C.
Synlett 2012, 23, 468–472
© Thieme Stuttgart · New York

LETTER
Addition of Cyclic b-Haloenals to Aromatic Aldehydes
471
O
HF or H2O
O–
Cl
Cl
OH Cl
H+
R
CHO
CHO
–O
R
R
Cl
O
H
H
3
II
III
F– or OH–
1a
Scheme 4 Proposed pathway for the direct VA reaction
cally demanding bromine or nitro group as ortho substit- for the decrease in the yield was the reduced electronega-
uent, the syn/anti ratio increased to 98:2 (Table 3, entries tivity of the bromine atom (Table 4, entry 2). The five-
3 and 4). The low reactivity of 2j or 2k was circumvented membered enals 1c and 1d could be smoothly converted
by increasing the temperature and prolonging the reaction into the desired products in modest yields with signifi-
time (Table 3, entries 9 and 10). However, the reactions cantly reduced diastereoselectivities, whereas the seven-
gave the mixtures of aldol and dehydration products in membered enal 1e was inactive, and no desired product
relative low yields with high diastereoselectivities. 2- was detected (Table 4, entries 3–5). The results showed
Napthylaldehyde (2k) provided an obvious improvement that the reaction rates were related to the structural effects
in the syn/anti ratio over that examined in benzaldehyde, of these generated dienolates in situ,13 and the six-mem-
similar to the described ortho-substitution effect. The het- bered dienolates exhibited the highest reactivities and di-
eroaromatic 2-furaldehyde (2l), where the furan ring was astereoselectivities in the VA reaction.
spatially less demanding and more electron-rich than the
phenyl ring, caused a drop in syn/anti ratio and generated
a trace dehydration product 4al (Table 3, entry 11). Alde-
hyde 2m failed to give the desired product due to its unre-
The above results indicated that the high regioselectivity
of nucleophilic addition for these exocyclic dienolates are
strongly dependent on the different kind of electrophilic
reagents. Obviously, TBAF containing a rather large tet-
activity under the reaction conditions (Table 3, entry 12).
rabutylammonium cation also tends to favor the formation
In addition, various cyclic b-haloenals 1b–e were also in- of the homoallylic alcohol 3 when an aromatic aldehyde
vestigated (Table 4). In the reaction of cyclic b-bromide was used as electrophile.
enal 1b, modest yield and high diastereoselectivity were
observed for the aldol product 3ba. The increase in syn se-
lectivity was presumably due to the bromine atom being
larger than the chlorine atom, and, more likely, the reason
The stereochemical outcome can be explained by examin-
ing possible transition states from the Newman projec-
tions IV and V (Figure 2). It is clear that when cyclic b-
halo enal was used as dienolate equivalents, the transition
state (TS) for conformer IV has fewer steric interactions
than that of the TS for conformer V, affording predomi-
nantly the syn product instead of the anti product. Non-
bonding steric interactions between substituted aromatic
ring and the X (Cl or Br) atoms would increase in the pro-
posed TS conformer V. Additionally, for ortho-, para-,
and meta-substituted benzaldehydes, the ortho-substitut-
ed aromatic rings show increased preference for the syn
adducts. For instance, when Cl, Br or NO2 as the ortho
substituent is present on the benzene ring (Table 3, entries
2–4), the syn-selectivity ratio is improved markedly to
97:3 and 98:2, respectively, presumably owing to the ad-
ditional steric demands of the ortho substituents.
Table 4 Direct Vinylogous Aldol Reaction of Various Cyclic b-Ha-
loenals with 2,4-Dichloroaldehydea
CHO
X
OH
Cl
n
X
1
TBAF
+
CHO
DMSO, 18 °C
Cl
n
Cl
3
Cl
CHO
n = 1, 2, 3
X = Cl, Br
2a
Entry
n
2
2
1
1
3
X
Time
Product 3 Yield (%)b dr (syn/anti)c
O– +NBu4
+NBu4
O–
1
2
3
4
5
Cl
Br
Cl
Br
Cl
3 min
12 min
5 min
26 min
24 h
3aa
3ba
3ca
3da
–
86
67
62
45
–
98:2
99:1
78:22
79:21
–
Cl
H
Cl
Ar
Ar
H
O
O
IV (syn product)
V (anti product)
Figure 2 The Newman projections of possible transition-state con-
formers IV and V
a Unless otherwise indicated, reactions were performed on a 0.50
mmol scale of 1 using 0.65 mmol of 2a and 90 mol% TBAF in 3.0 mL
DMSO.
In conclusion, we have developed a direct vinylogous al-
dol addition of cyclic b-halo enals with aromatic alde-
hydes initiated with TBAF as a key reagent. The reaction
b Yields of isolated product.
c Determined by 1H NMR analysis.
© Thieme Stuttgart · New York
Synlett 2012, 23, 468–472

472
J. Zhang et al.
LETTER
(3) For VMA reactions, see: (a) Shinoyama, M.; Shirokawa, S.-
i.; Nakazaki, A.; Kobayashi, S. Org. Lett. 2009, 11, 1277.
(b) Shirokawa, S.-i.; Kamiyama, M.; Nakamura, T.; Okada,
M.; Nakazaki, A.; Hosokawa, S.; Kobayashi, S. J. Am.
Chem. Soc. 2004, 126, 13604. (c) Ehrlich, G.; Hassfeld, J.;
Eggert, U.; Kalesse, M. Chem. Eur. J. 2008, 14, 2232.
(d) Hassfeld, J.; Kalesse, M. Tetrahedron Lett. 2002, 43,
5093. (e) Bhatt, U.; Christmann, M.; Quitschalle, M.; Claus,
E.; Kalesse, M. J. Org. Chem. 2001, 66, 1885. (f) Hassfeld,
J.; Christmann, M.; Kalesse, M. Org. Lett. 2001, 3, 3561.
(g) Christmann, M.; Bhatt, U.; Quitschalle, M.; Claus, E.;
Kalesse, M. Angew. Chem. Int. Ed. 2000, 39, 4364.
(h) Perreault, S.; Spino, C. Org. Lett. 2006, 8, 4385.
(i) Eissler, S.; Nahrwold, M.; Neumann, B.; Stammler, H.-
G.; Sewald, N. Org. Lett. 2007, 9, 817. (j) Zou, B.; Long,
K.; Ma, D. Org. Lett. 2005, 7, 4237. (k) Suenaga, K.;
Mutou, T.; Shibata, T.; Itoh, T.; Fujita, T.; Takada, N.;
Hayamizu, K.; Takagi, M.; Irifune, T.; Kigoshi, H.; Yamada,
K. Tetrahedron 2004, 60, 8509. (l) Hassfeld, J.; Kalesse, M.
Synlett 2002, 2007.
is carried out under mild conditions, and the operation is
simple and practical. This unprecedented chemical trans-
formation affords highly functionalized homoallylic alco-
hols having two stereocenters at the g- and d-positions
with a high diastereomeric ratio, which can be easily
transformed into other useful building blocks and are also
synthetically attractive in biological active molecules.
Current efforts focus on expanding the scope of the viny-
logous donors and acceptors as well as exploring the ap-
plications of the homoallylic alcohols in organic
synthesis, and the results will be reported in due course.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett. Included are
experimental procedures, analysis of NMR spectra of homoallylic
alcohols 3, and crystal data for compound syn-3aa.
(4) For direct VA reactions, see: (a) Bella, M.; Piancatelli, G.;
Squarcia, A.; Trolli, C. Tetrahedron Lett. 2000, 41, 3669.
(b) Bella, M.; Piancatelli, G.; Squarcia, A. Tetrahedron
2001, 57, 4429. (c) Sarma, K. D.; Zhang, J.; Curran, T. T.
J. Org. Chem. 2007, 72, 3311.
(5) For asymmetric direct VA reactions, see: (a) Yang, Y.;
Zheng, K.; Zhao, J.; Lin, L.; Liu, X.; Feng, X. J. Org. Chem.
2010, 75, 5382. (b) Ube, H.; Shimada, N.; Terada, M.
Angew. Chem. Int. Ed. 2010, 49, 1858. (c) Luo, J.; Wang,
H.; Han, X.; Xu, L.-W.; Kwiatkowski, J.; Huang, K.-W.; Lu,
Y. Angew. Chem. Int. Ed. 2011, 50, 1861. (d) Pansare, S.
V.; Paul, E. K. Chem. Commun. 2011, 47, 1027.
Acknowledgment
Financial support from National Natural Science Foundation of
China (No. 21172082) and characterization of the new compounds
for the Center of Analysis and Testing of Huazhong University of
Science and Technology is gratefully acknowledged.
References and Notes
(1) For VA reaction in synthesis of natural products and
biologically active compounds, see: (a) Abramite, J. A.;
Sammakia, T. Org. Lett. 2007, 9, 2103. (b) Jahn, U.; Dinca,
E. Chem. Eur. J. 2009, 15, 58. (c) Miesch, L.; Rietsch, V.;
Welsch, T.; Miesch, M. Tetrahedron Lett. 2008, 49, 5053.
(d) Vaz, B.; Alvarez, R.; Brückner, R.; De Lera, A. R. Org.
Lett. 2005, 7, 545. (e) Wu, T. J.; Huang, P. Q. Tetrahedron
Lett. 2008, 49, 383. (f) Liu, G.; Wu, T. J.; Ruan, Y. P.;
Huang, P. Q. Chem. Eur. J. 2010, 16, 5755. (g) Hunter, R.;
Rees-Jones, S. C. M.; Su, H. Tetrahedron Lett. 2007, 48,
2819. (h) Nomiya, M.; Murakami, T.; Noboru, T.; Okuno,
T.; Harada, Y.; Hashimoto, M. J. Org. Chem. 2008, 73,
5039. (i) Teixeira, R. R.; Barbosa, L. C. A.; Santana, J. O.;
Veloso, D. P.; Ellena, J.; Doriguetto, A. C.; Drew, M. G. B.;
Ismail, F. M. D. J. Mol. Struct. 2007, 837, 197. (j) Barbosa,
L. C. A.; Rocha, M. E.; Teixeira, R. R.; Maltha, C. R. A.;
Forlani, G. J. Agric. Food. Chem. 2007, 55, 8562.
(6) Adamo, M. F. A.; Suresh, S. Tetrahedron 2009, 65, 990.
(7) (a) Aponte, J. C.; Hammond, G. B.; Xu, B. J. Org. Chem.
2009, 74, 4623. (b) Xu, B.; Hammond, G. B. Angew. Chem.
Int. Ed. 2008, 47, 689.
(8) Lautens, M.; Han, W.; Liu, J. H.-C. J. Am. Chem. Soc. 2003,
125, 4028.
(9) (a) Liu, K.; Chougnet, A.; Woggon, W.-D. Angew. Chew.
Int. Ed. 2008, 47, 5827. (b) Lesch, B.; Toräng, J.;
Vanderheiden, S.; Bräse, S. Adv. Synth. Catal. 2005, 347,
555. (c) Volz, N.; Bröhmer, M. C.; Nieger, M.; Bräse, S.
Synlett 2009, 550.
(10) (a) Saito, S.; Shiozawa, M.; Ito, M.; Yamamoto, H. J. Am.
Chem. Soc. 1998, 120, 813. (b) Saito, S.; Nagahara, T.;
Shiozawa, M.; Nakadai, M.; Yamamoto, H. J. Am. Chem.
Soc. 2003, 125, 6200.
(11) Zhang, J.-L.; Gong, Y.-F. Org. Lett. 2011, 13, 176.
(12) CCDC 825960 contains the supplementary crystallographic
data for this paper. These data can be obtained free of charge
from The Cambridge Crystallographic Data Center via
www.ccdc.cam.ac.uk/data_request/cif.
(13) (a) Hawkinson, D. C.; Wang, Y. J. Org. Chem. 2007, 72,
3592. (b) Whalen, D. L.; Weimaster, J. F.; Ross, A. M.;
Radhe, R. J. Am. Chem. Soc. 1976, 98, 7319.
(k) Boukouvalas, J.; McCann, L. C. Tetrahedron Lett. 2010,
51, 4636. (l) Paterson, I.; Davies, R. D. M.; Marquez, R.
Angew. Chem. Int. Ed. 2001, 40, 603. (m) Tiseni, P. S.;
Peters, R. Org. Lett. 2008, 10, 2019.
(2) For reviews of VA reaction, see: (a) Casiraghi, G.; Zanardi,
F.; Appendino, G.; Rassu, G. Chem. Rev. 2000, 100, 1929.
(b) Denmark, S. E.; Heemstra, J. R. Jr.; Beutner, G. L.
Angew. Chem. Int. Ed. 2005, 44, 4682. (c) Kalesse, M. Top.
Curr. Chem. 2005, 244, 43. (d) Casiraghi, G.; Battistini, L.;
Curti, C.; Rassu, G.; Zanardi, F. Chem. Rev. 2011, 111,
3076.
Synlett 2012, 23, 468–472
© Thieme Stuttgart · New York

Copyright of Synlett is the property of Georg Thieme Verlag Stuttgart and its content may not be copied or
emailed to multiple sites or posted to a listserv without the copyright holder's express written permission.
However, users may print, download, or email articles for individual use.