A practical procedure of propargylation of aldehydes

Article abstract of DOI:10.1016/j.tetlet.2012.07.021

An operationally simple procedure of propargylation of aldehydes in moist solvent (distilled THF) has been developed through direct addition of propargyl bromide to aldehyde substrates mediated with low valent iron or tin. The metals were spontaneously pr

Full text of DOI:10.1016/j.tetlet.2012.07.021

Tetrahedron Letters 53 (2012) 5202–5205
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A practical procedure of propargylation of aldehydes
⇑
Papiya Ghosh, Angshuman Chattopadhyay
Bio-Organic Division, Bhabha Atomic Research Center, Mumbai 400085, India
a r t i c l e i n f o
a b s t r a c t
Article history:
An operationally simple procedure of propargylation of aldehydes in moist solvent (distilled THF) has
been developed through direct addition of propargyl bromide to aldehyde substrates mediated with
low valent iron or tin. The metals were spontaneously prepared in situ employing bimetal redox strategy.
Using different aldehydes as substrates (3a–k) both these metal mediated reactions took place producing
homopropargyl alcohols (4a–k) in good yields in all cases and with high chemoselectivity in most of the
cases (Table 1). Due to its efficacy, operational simplicity, performance in moist solvent, and being com-
prised of the use of inexpensive metal/metal salts, the procedure is practically viable and potentially
scalable.
Received 16 May 2012
Revised 4 July 2012
Accepted 6 July 2012
Available online 20 July 2012
Keywords:
Homopropargyl alcohol
Propargylation
Low valent metal
Bimetal redox reaction
Regioselectivity
Spontaneity
Ó 2012 Elsevier Ltd. All rights reserved.
Generality
Practical viability
Homopropargyl alcohol is an important functionality in organic
synthesis. The presence of alkyne unit in it makes it amenable for
versatile chemical maneuver that could be useful for important or-
ganic transformations.1 Many chiral homopropargylic alcohols
were treated as useful building blocks for the synthesis of different
complex molecules of pharmaceutical interest and many bioactive
natural products.2
plex,9 addition of 1-substituted propargyl mesylate to carbonyls in
the presence of SnI2/TBAI/NaI etc. In addition, there was a report
for propargylation of carbonyls by electrochemical reaction using
platinum cathode and zinc or aluminum anode.11 It has been ob-
served, many of these metal related propargylations of aldehydes
(3) were associated with the formation of the desired homopropar-
gylic alcohol (4) together with the undesired allenic (5) alcohols to
varied extents. This was caused by the metallotropic rearrange-
ments between propargyl metal and the corresponding allenyl me-
tal (Scheme 1, Eq. (iv)) during the reaction. However, the
regioselectivity in the formation of homopropargyl alcohol has
been improved during propargyl-Grignard reaction of carbonyls
by adding poisonous HgCl2 catalyst since early days or performing
the reaction in the presence of ZnBr212 following a careful reaction
protocol. In another remarkable approach, homopropargylic alco-
hol could be prepared with high regio-selectivity during the reac-
tion of carbonyls with allenylmetals.3,13 Needless to say, the
preparation of homopropargyl alcohol by metal mediated Barbier
type addition of propargyl bromide to aldehydes is always desir-
able from a practical viewpoint. In this regard, besides the accom-
plishment of various procedures for the preparation of
homopropargyl alcohol as mentioned above,3–13 there is a scope
to explore the potentials of other metals also in their different
forms regarding their ability to promote direct addition of propar-
gyl bromide to aldehydes.
Barbier type nucleophilic addition of functionalized halides to
carbonyls mediated with metals or metal compounds is treated
as an important strategy for carbon–carbon bond formation in or-
ganic synthesis. Accordingly, since the days of yore synthetic
chemists continued to explore the potentials of various metals
and their compounds to promote addition reactions between a
variety of organic halides and carbonyls. In the same vein, consid-
erable attention has been focused on the preparation of homoprop-
argyl alcohol through Barbier type addition of simple/
functionalized propargyl bromide to aldehydes/ketones aided by
different metals and their compounds. As a result, reports are
available regarding asymmetric3 as well as non-asymmetric prop-
argylation of carbonyls promoted directly by metals like indium,4
zinc,5 low valent barium6 etc. Also, reports are available for the
preparation of homopropargyl alcohols in other manners viz.
through zinc catalyzed addition of propargyl boronates to alde-
hydes,7 by manganese mediated asymmetric propargylation of
aldehydes catalyzed by Cr(salen) complex8 or titanocene (III) com-
In recent years, we have been working on performing Barbier
type addition reactions of organic halides to carbonyls in moist sol-
vent following practically viable procedures.14 Among them, we
⇑
Corresponding author.
E-mail address: achat@barc.gov.in (A. Chattopadhyay).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.07.021

P. Ghosh, A. Chattopadhyay / Tetrahedron Letters 53 (2012) 5202–5205
5203
ent work, we wished to explore the viability of this strategy for
direct addition of propargyl bromide to aldehydes as shown in
Scheme 1. In this mission, the reactions between propargyl bro-
mide and a number of aldehydes (3a–k) in distilled THF were at-
tempted16 using zinc dust as a common reducing metal in three
different combinations of M1X/M2, viz. (a) FeCl3/Zn, (b)
SnCl2ꢀ2H2O/Zn, and (c) CuCl2ꢀ2H2O/Zn. With a view to studying
the generality of this procedure we performed the reaction with
several aromatic (3a–f) and aliphatic aldehydes (3g–k) of varied
chain lengths (as shown in Table 1). To ensure the completion of
the reactions, each aldehyde (1.0 equiv) was stirred with excess
of zinc dust (3.0 equiv), metal salts (3.0 equiv), and propargyl bro-
mide (3.0 equiv).
All the aldehydes (3a–k) reacted nicely, albeit at different rates
using FeCl3/Zn or SnCl2ꢀ2H2O/Zn giving good yields of the products.
The progress of the reactions could be monitored by TLC on stirring
each reaction mixture for the periods as shown in Table 1. Among
all substrates, two aromatic (3a,d) and three aliphatic (3g,h,i) alde-
hydes reacted faster, while the others reacted somewhat sluggishly
in the presence of both the low valent metals. About the regio-
selectivity in this procedure,17,18 all aldehydes (3a–k) yielded the
corresponding homopropargyl alcohols (4a–k) as the major prod-
ucts (Table 1). Among them, only in two cases the reactions took
place with moderate regio-selectivity viz. tin mediated reactions
of 4-bromobenzaldehyde (3d) and n-heptanal (3h) (Table 1, entries
D & H), while in the other reactions it was very high. It is worth
noting, in five cases the reactions took place with the formation
of homopropargyl alcohols only viz. tin mediated reaction of 3a,
3e, and 3f and iron mediated reaction of 3b and 3c. Interestingly,
the corresponding reactions of all these five aldehydes with the
other low valent metals, produced homopropargyl alcohols in
slightly less than absolute regio-selectivity. Unfortunately, no reac-
tion took place with any of the aldehydes (3a–k) when
CuCl2ꢀ2H2O/Zn combination was used. This suggested that low va-
lent iron and tin, prepared in this manner proved to be good medi-
ators for propargylation of aldehydes in such wet condition, while
low valent copper did not.
(i)
( low valent )
+
+
M2
M2X
M1
M1X
M1X
, FeCl3; CuCl2.2H2O; SnCl2.2H2O; M2, Zn
R'
R
R'CHO (3)
RM1X
( low valent )
(ii)
RX
1
+
M1
OH
4
2
The present work :
+
M1
(iii)
Br
M1Br
2
1
R'CHO (3)
R'CHO (3)
R'
OH
(iv)
M1Br
2
4
C
2'
C
R'
OH
(v)
M1Br
5
Scheme 1. Low valent metal mediated propargylation of aldehydes.
developed a simple strategy to perform several important C–C
bond forming reactions between an organic halide (RX, 1) and an
aldehyde (3) in distilled THF mediated with several low valent
metals (M1).14b–h In this approach a low valent metal mediator
(M1) was prepared afresh in situ in highly active form following
a spontaneous bimetal redox reaction between its commercially
available hydrated or moist salt (M1X) with a reducing metal
(M2) (zinc dust14b–d,f,h or magnesium14e,g in distilled THF
(Scheme 1, Eq. (i)). Subsequently, the freshly prepared M1 in its
highly active form immediately reacted with halide (1) in wet con-
dition15 to produce the corresponding organometallic (2) which
was then involved in nucleophilic addition to aldehyde (3) to yield
the corresponding addition product (4) (Scheme 1, Eq. (ii)). So far,
this strategy has been utilized to develop several important C–C
bond forming reactions, viz. allylation,14c,d crotylation,14b,f,h Refor-
matsky reaction,14e and benzylation14g of aldehydes. For the pres-
The success of all these propargylation reactions (Table 1)
clearly demonstrated the compatibility of both low valent iron
and tin, prepared in this manner with the overall transformation
under such condition that comprised of two steps, viz. (a) prepara-
Table 1
Propargylation of aldehydes using Zn/FeCl3 and Zn or SnCl2ꢀ2H2O
Entry
A
Aldehyde
M2X
Time (h)
3
Yield (%)
75
4:5a
M2X
Time (h)
5
Yield (%)
81
4:5a
PhCHO (3a)
FeCl3
4a:5a
95.2:4.8
4b:5b
100:0
4c:5c
100:0
4d:5d
85.4:14.6
4e:5e
94.3:5.7
4f:5f
92.6:7.4
4g:5g
86.2:13.8
4h:5h
94.3:5.7
4i:5i
94.3:5.7
4j:5j
SnCl2ꢀ 2H2O
4a:5a
100:0
4c:5c
87.8:12.2
4c:5c
89.3:10.7
4d:5d
54.3:45.7
4e:5e
100:0
4f:5f
100:0
4g:5g
87.7:12.3
4h:5h
67.5:32.5
4i:5i
93.4:6.6
4j:5j
90.9:9.1
4k:5k
B
C
D
E
F
3-Br-PhCHO (3b)
3-MeOPhCHO (3c)
4-Br-PhCHO (3d)
4-Et-PhCHO (3e)
4-EtOPhCHO (3f)
n-C4H9CHO (3g)
n-C6H13CHO (3h)
n-C8H17CHO (3i)
n-C9H19CHO (3j)
n-C11H23CHO (3k)
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
14
14
3
84
81
81
89
80
79
77
95
98
93
SnCl2ꢀ 2H2O
SnCl2ꢀ 2H2O
SnCl2ꢀ 2H2O
SnCl2ꢀ 2H2O
SnCl2ꢀ 2H2O
SnCl2ꢀ 2H2O
SnCl2ꢀ 2H2O
SnCl2ꢀ 2H2O
SnCl2ꢀ 2H2O
SnCl2ꢀ 2H2O
14
14
5
81
87
85
86
81
73
81
83
97
92
15
16
1
16
14
3
G
H
I
4
7
4
8
J
16
18
17
18
95.2:4.8
4k:5k
97.1:2.9
K
82.6:17.4
a
Determined from 1H NMR spectra of the products.17,18

5204
P. Ghosh, A. Chattopadhyay / Tetrahedron Letters 53 (2012) 5202–5205
4. (a) Loh, T.-P.; Lin, M.-J.; Tan, K.-L. Tetrahedron Lett. 2003, 44, 507; (b) Haddad, T.
D.; Hirayama, L. C.; Buckley, J. J.; Singaram, B. J. Org. Chem. 2012, 77, 889. and
references cited therein; (c) Miao, W.; Chan, T. S. Synthesis 2003, 785; (d) Lin,
M.-J.; Loh, T. P. J. Am. Chem. Soc. 2003, 125, 13042; (e) Mia, W.; Lu, W.; Chan, T.
H. J. Am. Chem. Soc. 2003, 125, 2412.
5. (a) Bieber, L. W.; da Silva, M. F.; da Costa, R. C.; Silva, L. O. S. Tetrahedron Lett.
1998, 39, 3655; (b) Jpgi, A.; Maeorg, U. Molecules 2001, 6, 964.
6. Yanagisawa, A.; Suzuki, T.; Koide, T.; Okitsu, S.; Arai, T. Chem. Asian. J. 2008, 3,
1793.
7. Fandrick, D. R.; Fandrick, K. R.; Reeves, J. T.; Tan, Z.; Johnson, C. S.; Lee, H.; Song,
J. J.; Yee, N. K.; Sananayake, C. H. Org. Lett. 2010, 12, 88.
8. Bandini, M.; Gozzi, P. G.; Melchiorre, P.; Tino, R.; Umani-Ronchi, A. Tetrahedron:
Asymmetry 2001, 12, 1063.
9. Justicia, J.; Sancho-Sanz, I.; Alvarez-Manzaneda, E.; Oltra, J. E.; Cuerva, J. M. Adv.
Synth. Catal. 2009, 351, 2295.
10. Masuyama, Y.; Watabe, A.; Ito, A.; Kurusu, Y. Chem. Commun. 2009, 2000.
11. Kurono, N.; Sugita, K.; Tokuda, M. Tetrahedron 2000, 56, 847.
12. Achartya, H. P.; Miyoshi, K.; Kobayashi, Y. Org. Lett. 2007, 9, 3535.
13. (a) Marshall, J. A. J. Org. Chem. 2007, 72, 8153; (b) Denmark, S. D.; Fu, J. Chem.
Rev. 2003, 103, 2773. and references cited therein; (c) Marshall, J. A.; Gung, B.
W.; Grachan, M. L. In Modern Allene Chemistry; Krause, N., Hashni, A. S. K., Eds.;
Wiley-VCH: Weinheim, 2004; Vol. 1, p 493; (d) Gung, B. W. Org. React. 2004, 64,
1; (e) Patman, R. L.; Williums, V. M.; Bower, J. F.; Kische, M. J. Angew. Chem., Int.
Ed. 2008, 47, 5220. and references cited therein.
tion of propargyl metal (2) (Scheme 1, step iii), (b) reaction of 2
with aldehyde (3) (Scheme 1, step iv). The predominant formation
of homopropargyl alcohols (4) (Table 1) observed in all the low va-
lent iron and tin mediated reactions following this procedure could
be due to better affinity of both propargyl-iron and propargyl-tin to
react with aldehyde substrates (3) (Scheme 1, step iv), compared to
their degree of inter conversion into the corresponding allenyl me-
tal (20) that leads to the formation of allenyl alcohol (5) (Scheme 1,
step v). Hence, in each reaction the regioselectivity depends on the
difference in the formation of 4 and 5 that could be explained from
the degree of inter conversion between 2 and 20 which was pre-
sumably governed by the combination of low valent metal and
substrate associated with the reaction. The absolute failure of
low valent copper to mediate this reaction with all aldehydes
(3a–k) indicated its non reactivity with propargyl bromide at the
beginning to produce propargyl-copper (2) (Scheme 1, step iii) un-
der such reaction condition, which was unlike its marked involve-
ment in other reactions done earlier.14b–d,f
Thus, spontaneously occurring bimetal redox reactions between
a reducing metal and a reducible metal salt have been elegantly
exploited once again to develop a very practical method of propar-
gylation of aldehydes in moist solvent.15 This has been demon-
strated here by performing this reaction with a number of
aldehydes (3a–k) mediated with low valent iron or tin which were
prepared in situ using two different metal/metal salt combinations
viz. Zn/FeCl3 and Zn/SnCl2ꢀ2H2O. The efficacy of this procedure is
due to its operational simplicity as it involves only stirring the
reaction mixture at ambient temperature without the need of
any external energy like heating or sonication or electrical. From
all these aspects, this procedure is highly relevant with the recent
attention on performing organic reactions in environmentally be-
nign aqueous/wet media, salt solutions19 that are done with mod-
erate consumption of additional energy. The generality of this
procedure is realized from its marked success with different kinds
of aldehydes (3a–k) used in this work. Besides this, a highly attrac-
tive feature of this procedure is high degree of regioselectivity (Ta-
ble 1) in almost all reactions done here. Furthermore, the overall
procedure could be potentially scalable due to its operational sim-
plicity, performance in such wet medium, and high inexpensive-
ness of zinc dust and metal salts used here. Based on the present
findings, there is a scope to explore the viability of this approach
to perform this reaction using different other metal/metal salt
(M1/M2X) combinations.
14. (a) Chattopadhyay, A.; Salaskar, A. Synthesis 2000, 561; (b) Chattopadhyay, A.;
Goswami, D.; Dhotare, B. Tetrahedron Lett. 2006, 47, 4701; (c) Dhotare, B.;
Chattopadhyay, A. Tetrahedron Asymmetry 2009, 20, 2007; (d) Vichare, P.;
Chattopadhyay, A. Tetrahedron Asymmetry 2008, 19, 598; (e) Chattopadhyay,
A.; Dubey, A. J. Org. Chem. 2007, 72, 9357; (f) Chattopadhyay, A.; Goswami, D.;
Dhotare, B. Tetrahedron Lett. 2010, 51, 3893; (g) Dubey, A. K.; Goswami, D.;
Chattopadhyay, A. ARKIVOC 2010, 137; (h) Gowami, D.; Chattopadhyay, A. Lett.
Org. Chem. 2006, 3, 922.
15. The reasonable amount of moisture content in distilled THF makes it
sufficiently wet to cause partial (Cu) and good (Fe and Sn) solubility of the
metal salts in this solvent. This in turn facilitates the possible bimetal redox
reactions (Scheme 1, step i) and subsequent C–C bond forming reactions
(Scheme 1, step ii). This could be realized by the fact that no reaction took place
earlier14b–h when it was attempted in anhydrous THF employing this strategy.
16. General procedure of propargylation of aldehydes: A mixture of aldehyde 3
(0.01 mol), propargyl bromide (3.57 g, 0.03 mol), and FeCl3 (4.86 g, 0.03 mol for
iron mediated reaction) or SnCl2–2H2O (6.75 g, 0.03 mol for tin mediated
reaction) or CuCl2–2H2O (5.1 g, 0.03 mol for copper mediated reaction) in THF
(100 mL) was stirred thoroughly in
a water bath at around 10–15 °C
(maintained by addition of pieces of ice). After stirring the mixture for
10 min. zinc dust (Aldrich make, 1.95 g, 0.03 mol) was added in a few portions
over a period of 15 min. The mixture was stirred at the ambient temperature
for the period as shown in Table. It was then treated successively with diethyl
ether (100 mL) and water (50 mL), stirred for 10 min more and then filtered.
The filtrate was treated with 2% aqueous HCl to dissolve a little amount of
suspended particles. The organic layer was separated. The aqueous layer was
extracted with EtOAc. The combined organic layer was washed with water,
brine, and then dried. Solvent removal under reduced pressure afforded the
crude residue which was passed through a short silica gel pad eluting with 20%
EtOAc in petroleum ether to obtain a fraction containing the mixture of
homopropargyl (4) and allenyl (5) alcohols only. The eluent was concentrated
under reduced pressure for its NMR analysis.
17. 1H NMR spectra (CDCl3) of crude propargylation products of 3a–k mediated
with low valent iron and tin: (4a & 5a): For FeCl3/Zn (Table 1, entry A): d 2.07
(t, J = 2.6 Hz, 1H), 2.40 (bs, 1H), 2.62–2.68 (m, 2H), 4.87 (t, J = 6.3 Hz, 1H), 4.93
(m, 0.1H), 5.29 (m, 0.05H), 5.45–5.46 (m, 0.05 H), 7.2–7.6 (m, 5H). For
SnCl2ꢀ2H2O/Zn (Table 1, entry A): d 2.07 (t, J = 2.6 Hz, 1H), 2.40 (bs, 1H), 2.63–
2.64 (m, 2H), 4.87(t, J = 6.3 Hz, 1H), 7.2–7.5 (m, 5H); (4b & 5b): for FeCl3/Zn
(Table 1, entry B): d 2.09 (t, J = 2.6 Hz, 1H), 2.60–2.64 (m, 2H), 4.2 (bs, 1H), 4.85
(t, J = 6.3 Hz, 1H), 7.2–7.6 (m, 4H). For SnCl2ꢀ2H2O/Zn: (Table 1, entry B): d 2.09
(t, J = 2.6 Hz, 1H), 2.60–2.63 (m, 2H, overlapped with bs, 1H), 4.83 (t, J = 6.2 Hz,
1H), 4.93–4.96 (m, 0.22 H), 5.28 m, 0.11 H), 5.36–5.42 (m, 0.11 H), 7.2–7.5 (m,
4H). (4c & 5c): For FeCl3/Zn (Table 1, entry C) d 2.08 (t, J = 2.7 Hz, 1H), 2.62–2.65
(m, 2H), 3.81 (s, 3H, overlapped with abs, 1H), 4.85 (t, J = 6.2 Hz, 1H), 6.8–
7.3.(m, 4H). For SnCl2ꢀ2H2O/Zn (Table 1, entry C): d 2.08 (t, J = 2.6 Hz, 1H), 2.38
(bs, 1H), 2.61–2.67 (m, 2H), 3.80 (s, 3H), 4.86 (t, J = 6.3 Hz, 1H), 4.93–4.95 (m,
0.24 H), 5.25–5.26 (m, 0.12H), 5.43–5.44 (m, 0.12H), 6.8–7.3. (m, 4H). (4d &
5d):. For FeCl3/Zn (Table 1, entry D): d 2.07 (t, J = 2.6 Hz, 1H), 2.4 (bs, 1H), 2.57–
2.63 (m, 2H), 4.81 (t, J = 6.3 Hz, 1H), 4.89–4.93 (m, 0.34H), 5.13–5.25 (m,
0.17H), 5.36–5.39 (m, 0.17H), 7.1–7.3 (m, 4H). For SnCl2ꢀ2H2O/Zn (Table 1,
entry D): d 2.05 (t, J = 2.6 Hz, 1H), 2.52–2.57 (m, 2H), 3.0 (bs, 1H), 4.84 (t,
J = 6.3 Hz, 1H), 4.85–4.89 (m, 1.68H), 5.12–5.26 (m, 0.84H), 5.32–5.38 (m,
0.84H), 7.1–7.5. (m, 4H). (4e & (5e):. For FeCl3/Zn (Table 1, entry E): d 1.25 (t,
J = 4.0 Hz, 3H), 2.08 (t, J = 2.6 Hz, 1H), 2.3 (bs, 1H), 2.5–2.7 (m, 4H), 4.86 (t,
J = 6.3 Hz, 1H), 4.92–4.94 (m, 0.12 H), 5.25–5.26 (m, 0.06H), 5.44–5.45 (m, 0.06
H), 7.1–7.3.(m, 4H). For SnCl2ꢀ2H2O/Zn (Table 1, entry E): d 1.25 (t, J = 4.0 Hz,
3H) 2.05 (t, J = 2.6 Hz, 1 H), 2.5–2.7 (m, 4H overlapped with a bs, 1H), 4.86 (t,
J = 6.3 Hz, 1H), 7.1–7.3. (m, 4H). (4f & 5f): For FeCl3/Zn (Table 1, entry F): d 1.34
(t, J = 4.0 Hz, 3H), 2.08 (t, J = 2.6 Hz, 1 H), 2.5–2.6 (m, 2 H), 3.96 (q, J = 6.8 Hz,
2H), 4.3 (bs, 1H), 4.73 (t, J = 6.3 Hz, 1H), 4.93 (m, 0.16H), 5.25–5.29 (m, 0.08 H),
5.42–5.44 (m, 0.08H), 6.81–6.87 (m, 2H), 7.18–7.28 (m, 2H). For SnCl2ꢀ2H2O/Zn
(Table 1, entry F): d 1.34 (t, J = 4.0 Hz, 3H), 2.02 (t, J = 2.6 Hz, 1H), 2.5–2.6 (m,
References and notes
1. (a) Yamamoto, H. In Comprehensive Organic Synthesis; Trost, B. M., Fleming, I.,
Heathcock, C. H., Eds.; Pergamon: Oxford, 1991; Vol. 2, p 81; (b) Epsztein, R. In
Comprehensive Carbanio Chemistry; Buncel, E., Durst, T., Eds.; Elsevier: New
York, 1984;
p 107. Chapter 3; (c) Kleinman, E. F.; Volkmann, R. A. In
Comprehensive Organic Synthesis; Trost, B. M., Fleming, I., Heathcock, C. H.,
Eds.; Pergamon: Oxford, 1991; Vol. 2, p 975; (d) Stang, P. J.; Diederich, F.
Modern Acetylene Chemistry; VCH: New York, 1995.
2. (a) Dolhem, F.; Al Tahali, F.; Lievre, C.; Demailly, G. Eur. J. Org. Chem. 2005, 23,
5019; (b) Bahadoor, A. B.; Micalizio, G. C. Org. Lett. 2006, 8, 1189; (c) Saito, N.;
Masuda Saito, H.; Takenouchi, K.; Ishizuka, S.; Namekawa, J.; Takimoto-
Kamimura, M.; Kitakka, A. Synthesis 2005, 2533; (d) Kobayishi, Y.; Fukuda, A.;
Kimachi, T.; Ju-Ichi, M.; Takemoto, Y. Tetrahedron 2005, 61, 2607; (e) Broadrup,
R. L.; Sunder, H. M.; Swindell, C. S. Bioorg. Chem. 2005, 33, 116; (f) Chavan, S. P.;
Praveen, C. Tetrahedron Lett. 2005, 46, 1939; (g) Schwartz, B. D.; Hayes, P. Y.;
Kitching, W.; De Voss, J. J. Org. Chem. 2005, 70, 3054; (h) Cases, M.; Gonzalez
lopez de Turiso, F.; Hadjisoterio, M. S.; Pattenden, G. Org. Biomol. Chem. 2005, 3,
2786; (i) Hansen, E. C.; Lee, D. Tetrahedron Lett. 2004, 45, 7151; (j) Marshall, J.
A.; Adams, N. D. Org. Lett. 2000, 2, 2897; (k) Yanagisawa, A.; Habaue, S.;
Yamamoto, H. J. Org. Chem. 1989, 54, 5200; (l) Carter, R. G.; Weldon, D. J. Org.
Lett. 2000, 2, 3913; (m) O’Sullivan, P. T.; Buhr, W.; Fuhry, M. A. M.; Harrison, J.
R.; Davies, J. E.; Feeder, N.; Marshall, D. R.; Burton, J. W.; Homes, A. B. J. Am.
Chem. Soc. 2004, 126, 2194; (n) Trost, B. M.; Dong, G. B. Nature 2008, 456, 485;
(o) Liu, S. B.; Kim, J. T.; Dong, G. C.; Kishi, Y. Org. Lett. 2009, 11, 4520; (p)
Francais, A.; Leyva, A.; Etxebarria-Jardi, G.; Ley, S. V. Org. Lett. 2010, 12, 340.
3. Reddy, L. J. Org. Lett 2012, 14, 1142. and references cited therein.

P. Ghosh, A. Chattopadhyay / Tetrahedron Letters 53 (2012) 5202–5205
5205
2H), 3.5 (bs, 1H), 3.96 (q, J = 6.8 Hz, 2H), 4.77 (t, J = 6.3 Hz, 1H), 6.81–6.87 (m,
2H), 7.18–7.28 (m, 2H). (4g & 5g): For FeCl3/Zn (Table 1, entry G): d 0.91 (t,
J = 3.5 Hz, 3H), 1.32–1.37 (m, 4H), 1.50–1.63 (m, 2H), 2.05 (t, J = 2.7 Hz, 1H),
2.33–2.45 (m, 2H, overlapped with a bs, 1H), 3.77 (m, 1H), 4.12–4.33 (m, 0.16
H), 4.85–4.90 (m, 0.32H), 5.24–5.43 (m, 0.16H). For SnCl2ꢀ2H2O/Zn (Table 1,
entry G): d 0.90 (t, J = 3.5 Hz, 3H), 1.32 (m, 4H), 1.5–1.6 (m, 2H), 2.05 (t,
J = 2.7 Hz, 1H), 2.30–2.42 (m, 2H), 3.2 (bs, 1H), 3.76 (m, 1H), 4.17 (m, 0.14 H),
4.85–4.92 (m, 0.28 H), 5.21–5.42 (m, 0.14 H). (4h & 5h): For FeCl3/Zn (Table 1,
entry H): d 0.88 (t, J = 2.2 Hz, 3H), 1.26–1.28 (m, 8H), 1.38–1.53 (m, 2H), 1.88
(bs, 1H), 2.04 (t, J = 2.6 Hz, 1H), 2.26–2.46 (m, 2H), 3.74–3.77 (m, 1H), 4.14–
4.17 (m, 0.48H), 4.83 -4.85 (m, 0.96H), 5.22–5.44 (m, 0.48H). For SnCl2ꢀ2H2O/
Zn (Table 1, entry H): d 0.87 (t, J = 3.0 Hz, 3H), 1.32 (m, 12H), 1.5–1.6 (m, 2H,
overlapped with a bs, 1H), 2.05 (t, J = 2.7 Hz, 1H), 2.30–2.39 (m, 2H), 3.75–3.76
(m, 1H), 4.19 (m, 0.07 H), 4.85 (m, 0.14H), 5.24 (m, 0.07H). (4i & 5i): For FeCl3/
Zn (Table 1, entry I): d 0.88 (t, J = 3.0 Hz, 3H), 1.33 (m, 12H), 1.5–1.6 (m, 2H), 1.7
(bs, 1H), 2.05 (t, J = 2.7 Hz, 1H), 2.33–2.45 (m, 2H), 3.74–3.77 (m, 1H), 4.11–
4.20 (m, 0.06H), 4.81–4.89 (m, 0.12H), 5.24–5.32 (m, 0.06H). For SnCl2ꢀ2H2O/Zn
(Table 1, entry I): d 0.87 (t, J = 3.0 Hz, 3H), 1.32 (m, 12H), 1.5–1.6 (m, 2H,
overlapped with a bs, 1H), 2.05 (t, J = 2.7 Hz, 1H), 2.3–2.4 (m, 2H), 3.74–3.77
(m, 1H), 4.11–4.20 (m, 0.07 H), 4.81–4.89 (m, 0.14H), 5.23–5.32 (m, 0.07H). (4j
& 5j): For FeCl3/Zn (Table 1, entry J): d 0.88 (t, J = 3.0 Hz, 3H), 1.2–1.3 (m, 14H),
1.52–1.55 (m, 2H, overlapped with a bs, 1H), 2.05 (t, J = 2.7 Hz, 1H), 2.33 2.45
(m, 2H), 3.73–3.77 (m, 1H), 4.15–4.17 (m, 0.05H), 4.83–4.86 (m, 0.1H), 5.20–
5.26 (m, 0.05H). For SnCl2ꢀ2H2O/Zn (Table 1, entry J): d 0.87 (t, J = 3.0 Hz, 3H),
1.2–1.3 (m, 14H), 1.52–1.54 (m, 2H), 2.06 (t, J = 2.7 Hz, 1H, overlapped with a
bs, 1H), 2.33–2.47 (m, 2H), 3.73–3.77 (m, 1H), 4.15–4.17 (m, 0.1H), 4.83–4.86
(m, 0.2H), 5.20–5.26 (m, 0.1H). (4k & 5k): For FeCl3/Zn (Table 1, entry K): d 0.88
(t, J = 3.0 Hz, 3H), 1.22–1.28 (m, 18H), 1.52–1.64 (m, 2H), 1.9 (bs, 1H), 2.05 (t,
J = 2.7 Hz, 1H), 2.30–2.44 (m, 2H), 3.74–3.77 (m, 1H), 4.17–4.20 (m, 0.03 H),
4.84–4.85 (m, 0.06 H), 5.24 (m, 0.03H). For SnCl2ꢀ2H2O/Zn (Table 1, entry K): d
0.88 (t, J = 3.0 Hz, 3H), 1.23–1.3 (m, 18H), 1.5–1.6 (m, 2H, overlapped with a bs,
1H), 2.05 (t, J = 2.6 Hz, 1H), 2.25 -2.39 (m, 2H), 3.70–3.79 (m, 1H), 4.17–4.21(m,
0.21H), 4.80–4.84 (m, 0.42H), 5.23–5.24 (m, 0.21H).
18. Regioselectivity of each reaction has been determined by comparing the
pertinent signals in the 1H NMR spectra of its residue obtained as above.17
19. (a) Li, C. J. Chem. Rev. 2005, 105, 3095. and references cited therein; (b) Li, C. J.;
Chan, T. H. Organic Reactions in Aqueous Media; Wiley: New York, 1997; (c)
Grieco, P. Organic Reactions in Water; Chapman & Hall: London, 1998; (d)
Mulzer, J.; Attenbach; Braun, M.; Reissig, H. Organic Synthesis Highlights; VCH:
Weinheim, 1991; (e) Petrier, C.; Luche, J. L. J. Org. Chem. 1985, 50, 910; (f) Li, C. J.
Chem. Rev. 1993, 93, 2023. and references cited therein; (g) Clean Solvents:
Alternate Media for Chemical Reactions and Processing: ACS Symp. Ser. 2002, 819
(Abraham, M. A.; Moens, L., Eds.).