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Tetrahedron 64 (2008) 2883e2896

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Tetrahedron report number 829

Halovinyl aldehydes: useful tools in organic synthesis

Sulagna Brahma, Jayanta K. Ray*
Department of Chemistry, Indian Institute of Technology, Kharagpur 721302, West Bengal, India
Received 26 November 2007
Available online 15 December 2007

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2884
2. Synthesis of chloro- and bromovinyl aldehydes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2884
3. Synthetic utility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2884
3.1. Synthesis of hydrindene butenolides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2884
3.2. Synthesis of polycyclic oxa-coumarins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2885
3.3. Synthesis of 5,6-dihydrobenz[f]isoquinolines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2885
3.4. Synthesis of non-natural cavity-shaped molecules . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2885
3.5. Synthesis of potential dihydrodiol metabolites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2885
3.6. Synthesis of substituted nicotine derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2887
3.7. Synthesis of indanones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2887
3.8. Synthesis of macrocyclic ligands . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2887
3.9. Synthesis of vic-diols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2887
3.10. Synthesis of receptors for the recognition of dicarboxylic acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2888
3.11. Synthesis of aromatics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2888
3.12. Synthesis of cyclopentanone-containing fused rings . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2889
3.13. Synthesis of azirines and isooxazoles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2890
3.14. Synthesis of various 2-substituted cryptolepines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2890
3.15. Synthesis of substituted benzene by homo/hetero-coupling of halovinyl aldehydes . . . . . . . . . . . . . . . . . . . . . . . . . . 2890
3.16. Synthesis of lactones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2891
3.17. Synthesis of substituted pyrazoles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2891
3.18. Synthesis of 1,2-disubstituted arylnaphthalenes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2892
3.19. Synthesis of alkenylpyrrole derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2892
3.20. Stereoselective synthesis of taxol C-ring . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2892
3.21. Synthetic approach toward substituted benzene derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2893
3.22. Synthesis of cuparenone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2893
3.23. Synthesis of various quinolines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2893
3.24. Synthesis of polycyclic quinolines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2894
4. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2894
Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2895
References and notes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2895
Biographical sketch . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2896

Abbreviations: Ac, acetyl; Ar, aryl; Bn, benzyl; Bu, butyl; DCM, dichloromethane; DDQ, dichloro dicyano quinone; TMEDA, tetramethylethylenediamine;
DIPEA, N,N-diisopropylethylamine; DMF, N,N-dimethylformamide; DMSO, dimethylsulfoxide; ee, enantiomeric excess; Et, ethyl; Me, methyl; Mes, mesyl;
Ms, mesityl; Pent, pentyl; Ph, phenyl; PIDA, phenyliodine diacetate; Pr, propyl; py, pyridyl; THF, tetrahydrofuran; TFA, trifluoroacetic acid.
* Corresponding author. Tel.: þ91 3222 283326; fax: þ91 3222 282252.
E-mail address: jkray@chem.iitkgp.ernet.in (J.K. Ray).

0040-4020/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2007.11.112
2884 S. Brahma, J.K. Ray / Tetrahedron 64 (2008) 2883e2896

1. Introduction
O
N
This report presents an overview of the synthesis and use of N
Ref. 10
halovinyl (chloro- and bromovinyl) aldehydes as synthetic N
N Ref. 9 R
tools in organic chemistry. Various groups have reported sig- Ref. 11
nificant contributions on halovinyl aldehydes and our review CHO
Ref. 8 Ref. 4
aims to give an overview of the latest advances in the chemis-
try of halovinyl aldehydes, from their preparation to their S Cl N
transformations and applications in organic synthesis. Ref. 5
Ref. 7
The present review focuses on the chemistry of halovinyl Ref. 6
aldehydes in the last 18 years from 1989 up to mid-2007, be- NR
cause these compounds are still of synthetic interest to organic N R S R
chemists.
O O

Figure 3.
2. Synthesis of chloro- and bromovinyl aldehydes

The VilsmeiereHaack reagent (POCl3þDMF) has attracted 3.1. Synthesis of hydrindene butenolides
the attention of synthetic organic chemists since its discovery
in 1927.1 One aspect of its importance is that its reaction with The bromo Vilsmeier reaction of hydrindanone provided a
a keto methylene group produces b-chloro-acroleins (the single crystalline bromo aldehyde 1. Addition of 3-butenyl-,
mechanism is shown in Fig. 1). Arnold and Zemlicka2 in 3,4-pentadienyl-, and (E)-4-pentenylmagnesium bromides to
1958 first reported the reaction of POCl3 and DMF with this aldehyde afforded mixtures (ratios 1.2e1.5:1) of epimeric
keto methylene compounds. bromo alcohols 2 and 3 (Scheme 1). The stereochemistry of
The bromo analogue of the Vilsmeier reaction was reported the bromo alcohols is assigned by analogy. Metalation of the
by Arnold and Holy,3 and the mechanism is shown in Figure 2. bromo alcohols with 3.5 equiv of tert-butyllithium followed
by inverse addition to carbon dioxide in THF at 78  C and
O hydrolysis afforded the corresponding alkenyl butenolides
O
Me2N-CHO + _ 4 and 5.
+ Me2N=CHCl·Cl2PO2 NMe2 + 2HCl
POCl3
+ + _
H
NMe2 Me2N=CHCl·Cl2PO2 Br
Cl H Cl O
+ + OHC
O NMe2 NMe2.2Cl- 1
Cl- R MgBr
H
Figure 1. H Br
Br
+
HO
HO
R
R
2 3
Br Br
Br R = CH2, 12a (55%) 12b (36%)
+ + Me2N CH 13b (28%)
Me2N C O PBr2 Me2N CH R = C=CH2, 13a (35%)
H O PBr2 R = CHCH3, 14a (35%) 14b (26%)
O PBr2
1. (CH3MgBr) 1. (CH3MgBr)
O
O R = CH2 tBuLi tBuLi
+ _ R = C=CH2 2. CO2 2. CO2
Me2N=CHBr·POBr2 NMe2 + 2HBr R = CHCH3 3. H3O+ 3. H3O+

_ O H O H
+ +
NMe2 Me2N=CHBr·POBr2 +
O O
Br O R
Br H R
+ + _ H 4 H
_ 2
NMe NMe2·2Br 5
O
Br R = H, 15a (75%) 15b (57%)
R = CH3, 16a (90%) 16b (90%)
Figure 2.
Scheme 1. Synthesis of hydrindene butenolides.

3. Synthetic utility Stereoisomeric 4,9a-dimethylhydrodicyclopenta[a,d]cyclo-

octen-1-ones related to ophiobolins and ceroplastins can be
Chloroaldehydes are important starting materials for entry synthesized via annelative ring expansion of hydrindene
into different heterocyclic systems (Fig. 3).5,6,9e11 precursors.12
 S. Brahma, J.K. Ray / Tetrahedron 64 (2008) 2883e2896 2885

3.2. Synthesis of polycyclic oxa-coumarins 3.4. Synthesis of non-natural cavity-shaped molecules

Ray et al.8 have described the synthesis of polycyclic oxa-
coumarins 9, 13, and 14 (potential antitumor agents) from
chloroaldehyde derivatives 6 and 10 (Schemes 2 and 3).
They first converted chloroaldehyde (6 or 10) to the methoxy
derivative (7 or 11) by refluxing with sodium methoxide in
methanol. Then methoxyaldehyde (7 or 11) on condensation
with cyanoacetic ester produced the nitrile derivative (8 or
12). They achieved the oxa-coumarin derivatives by heating
the nitrile derivatives with pyridine hydrochloride.
They used the chloroaldehydes for the synthesis of
naphthopyranoquinolines via regioselective thermal cycliza-
tion of enaminoimine hydrochloride derivatives. Ray et al.
also reported the synthesis of different quinolines,13,14
acridines,15 and polycyclic thiaarenes16 from different
chloroaldehydes.
Ray’s group has been active in synthesizing non-natural
cavity-shaped molecules 27 with selective cavity size and
with proper functionality in this region to interact selectively
with organic and inorganic substrates, starting from chloro-
aldehyde 23 of the appropriate ketone 2218 (Scheme 5).
Here, bis-chloroaldehyde (23) on refluxing with 2 equiv of
1-naphthylamine produced Schiff’s base 24. Thermolysis of
compound 24 afforded compound 25. Finally, aromatization
of 25 with DDQ/benzene furnished the desired compound
26, which on direct alkylation by alkyllithiums produced 27.
3.5. Synthesis of potential dihydrodiol metabolites
The carcinogenic activities of polycyclic aromatic hydro-
carbons are often strongly affected by the substitution of

Ph
3.3. Synthesis of 5,6-dihydrobenz[f]isoquinolines N

Ph
Gilchrist and Healy have used 1-bromo-3,4-dihydro-
NMe2
naphthalene-2-carboxaldehyde 15 for the preparation of 17
1-substituted-3,4-dihydronaphthalene-2-carboxaldehyde N,N- 16
dimethylhydrazones 16, 18, and 20. Dimethylhydrazones of S S
Br N
H
1-vinyl-3,4-dihydronaphthalene underwent electrocyclic ring CHO C NMe2
closure followed by loss of dimethylamine to give 5,6-dihy-
drobenz[f]isoquinolines 17, 19, and 21 (Scheme 4).17 15 18 19
The results established that N,N-dimethylhydrazones can be Me3Si
Me3Si
used as C]N components in elctrocyclic ring closure reac- N
NMe2
tions of 1-azatrienes. The dimethylhydrazono group has also
been shown to allow bromineelithium exchange at an adjacent 20
carbon atom, and this may be useful in expanding the scope of 21

the reaction. Scheme 4.

NC CO2Et
CHO CHO CO2Et
O a O b O c O

Cl OMe OMe O O

6 7 8 9

Scheme 2.

O O
c O
a b CO2Et
13
Cl OMe OMe
d

O O O
CHO CHO
10 11 12 O O
NC CO2Et
O

14

Scheme 3. Reagents and conditions: (a) NaOMe/MeOH/reflux; (b) CH2(CN)CO2Et/ethanolic KOH/reflux; (c) PhN$HCl/reflux, 15 min; (d) PhN$HCl/quinoline/
reflux.
2886 S. Brahma, J.K. Ray / Tetrahedron 64 (2008) 2883e2896

NH2
O O Cl Cl
OHC CHO
POCl3 -DMF
TEA Benzene

22 23

Cl Cl
290-300 °C N N
N N

24
25

DDQ n-BuLi
PhH N N THF-TMEDA N N
reflux
R R

26 27

Scheme 5.

fluorine in appropriate molecular sites.19 The presence of fluo-

rine at a suitable position can alter the conformation of two hy-
droxy groups to affect the mutagenic activity of trans diol
epoxide derivatives.20 Ray’s group has undertaken the synthe- X
H
NH2 N
sis of two potential dihydrodiol metabolites of two isomeric X
Cl
fluorobenz[c]acridines 28a,b (Scheme 6), as well as their par- + EtOH 200-250 °C
Y
ent fluoroazaarenes 29a,b (Scheme 7). HCl (cat)
CHO HN
Ray et al. reported21 the first synthesis of the hitherto unknown 38 Y 39a, b Cl
trans 9-fluoro-3,4-dihydroxy-3,4-dihydro-benz[c]acridine 28a 31a, b
X Y
and 11-fluoro-3,4-dihydroxy-3,4-dihydrobenz[c]acridine 28b,
as oxidative metabolites of 9- and 11-fluorobenzacridine deriv- X
X
atives in six high-yielding steps, starting from 1-chloro-6- N DDQ
N a. X = H, Y = F
methoxy-3,4-dihydronaphth-2-aldehyde 30. PhCl b. X = F, Y = H
Here, treatment of chloroaldehyde 30 with 2.5 equiv of flu- Y
Y
40a, b 29a, b
oroanilines 31a,b afforded arylenaminoimine hydrochlorides
32a,b. Thermal cyclization of 32a,b at 200e250  C furnished Scheme 7.

OMe OMe
MeO NH2 X X
H
Cl X N N
EtOH 200-250 °C
+
HCl
CHO Y Y
30 32a, b HN 33a, b
Y
Cl
31a, b
X Y

OMe OH O
X X X
DDQ N OMe
N aq HBr N PIDA
C6H5Cl OMe
reflux MeOH
Y Y Y
34a, b 35a, b 36a, b

O X OH
X
N
HCl (cat) N NaBH4 OH
O a. X = H, Y = F
AcOH-H2O EtOH b. X = F, Y = H
Y
Y
28a, b
37a, b

Scheme 6.
 S. Brahma, J.K. Ray / Tetrahedron 64 (2008) 2883e2896 2887

dihydrobenz[c]acridine derivatives 33a,b. Aromatization pro- consecutive intermolecular carbopalladation with an internal
duced 34a,b and subsequent demethylation of 34a,b generated alkyne and then intramolecular nucleophilic vinylpalladation
compounds 35a,b. Oxidation of 35a,b with PIDA resulted in of the aldehyde function to produce the indenol derivative
the formation of o-quinone monoketals 36a,b, which on hy- 49 in high yield. Further heating under more elevated temper-
drolysis with aq HCl in AcOH gave o-quinones 37a,b. Stereo- atures caused complete isomerization to the corresponding
selective reduction of this quinones with excess of sodium indanone 50 in 68% yield (Scheme 10).
borohydride afforded 28a,b.
In their studies, they found that trans dihydrodiols (28a and 5% Pd(OAc)2
CHO
28b) of the respective fluorobenz[c]acridines showed no de- + 1.5 n-Pr n-Pr
2 equiv. KOAc
crease in mutagenicity, compared to their parent fluoroazaar- 10 equiv. EtOH
Br DMF, 60 °C, 12 h
enes 29a and 29b, respectively. From the chloroaldehyde 38, 48

29a,b was prepared through 39a,b and 40a,b as per Scheme OH O

7. In addition, the presence of a fluorine atom in the non-inter- 24 h/100 °C
n-Pr n-Pr
active position of the dihydrodiols (28a and 28b) does not
reduce their mutagenicity, compared to the analogous 49 n-Pr 50 n-Pr
dihydrodiol of the unsubstituted benz[c]acridine. Scheme 10.

3.6. Synthesis of substituted nicotine derivatives

22
Kanomata and Nakata have investigated the reactivity and
synthetic utility of various 2-(phosphoranylideneamino)acryl-
aldehydes, formyl-substituted (vinylimino)phosphoranes, as
precursors for more generally substituted nicotine derivatives.
They described the preparation of several alkyl- and phenyl-
substituted 2-(phosphoranylideneamino)acraldehydes 44
from the formyl-substituted azirines 43 (Scheme 8) and their
reactions with acetylinic esters as unique synthetic approaches
to 2-mono- and 2,5-disubstituted nicotinate derivatives 45e47
(Scheme 9). Here, formyl-substituted azirines were obtained
from the corresponding chlorovinyl aldehyde 42 starting
from appropriate ketone 41.
The novel pyridine formation reaction of 2-(phosphoranyl-
ideneamino)acrylaldehydes 44 with acetylinic esters provides
a convenient method for the syntheses of 2-mono- and 2,5-di-
substituted nicotinate derivatives.
3.8. Synthesis of macrocyclic ligands
Ray’s group24 achieved the first synthesis of 18-membered
macrocyclic ligands based on a dibenz[c,h]acridine framework
58 (Scheme 11), from a b-chlorovinyl aldehyde derivative 52
of 7-bromo-1-tetralone 51, having a binding capability with
urea. Here, chlorovinylimine 53 was obtained from chloro-
vinyl aldehyde 52 on refluxing with 7-bromo-1-naphthyl-
amine. The thermal cyclization of chlorovinylimine
produced dihydrobenz[c,h]acridine derivative 54. Dehydroge-
nation of 54 with DDQ generated 2,12-dibromodibenz[c,h]-
acridine 55. The dibromo derivative was converted to
dialdehyde 56 by n-BuLi and DMF. This was condensed
with diethyltriamine to generate the macrocyclic compound
57. Finally, compound 57 on reduction with NaBH4 af-
forded 58, which has correct functionalities to bind the urea
molecule.

3.7. Synthesis of indanones 3.9. Synthesis of vic-diols

Gevorgyan et al.23 showed that o-bromobenzaldehyde 48, Shimizu et al.25 described the pinacol reaction of b-halo-
in the presence of a palladium catalyst, smoothly underwent genated a,b-unsaturated aldehydes 59 promoted by

O
DMF, POCl3 R1 CHO 1. NaN3, DMF N PPh3 R1 CHO
R2 CHO
R1 CH2Cl2 R2 2. Δ R2 toluene Ph3P N R
41 Cl R1
42a 43a Δ , 3-4 h 44a 2
42c 43b 44b
42d 43c 44c
43d 44d

a: R1 = Ph, R 2 = Me; b: R1 = Ph, R2 = H; c: R1 = n-Pr, R2 = Et; d: R1 = n-Bu, R2 = n-Pr

Scheme 8.

E E H
R1 CHO R2 CO2Me R2 CO2Me R2 CO2Me
E CO2Me
Ph3P N + +
R2 toluene, 140 °C
H N R1 R1 N H R1 N E
44 E = H, CO2Me
45 46 47

Scheme 9.
2888 S. Brahma, J.K. Ray / Tetrahedron 64 (2008) 2883e2896

Br Br NH2 Br
Br
POCl3, DMF
Cl
O TEA, Δ Cl PhH, reflux

CHO
51 52 53
N
Br Br Br Br

250-270 °C N DDQ
N n-BuLi, TMEDA
25 min PhCl, reflux, 20 h
THF, -78 °C
54 55
N N
CHO CHO H H
N N NH HN

N diethylenetriamine NaBH4
N N
PhH, reflux ethanol
rt
56
57 58

Scheme 11.

X X OH R2 3.10. Synthesis of receptors for the recognition of

CHO TiI4/EtCN R1 dicarboxylic acids
R1 R1
R2 R2 OH x
59 60 Studies of supramolecular systems designed as receptors
Scheme 12. with the capability to bind carboxylic acids have recently re-
ceived much attention. The hosteguest complexation studies
of the carboxylic acids and their derivatives with suitable re-
titanium tetraiodide to give the coupling products 60 in ceptors have become the central focus of the molecular recog-
good yields with high dl-selectivity (Scheme 12). Subsequent nition studies to mimic the biochemical processes.
reduction with H2/PdeC gave the saturated vic-diols in Ray et al.26,27 have designed and executed a number of for-
good yields. A Heck coupling reaction enabled the ceps-type receptors 66 and 67 containing oxygen, sulfur, and
displacement of the halogens with vinyl groups without the carbon at the pivot, and an amide functionality at the end
loss of stereochemical integrities. Results are tabulated in (Scheme 13) to selectively bind appropriately sized dicarbox-
Table 1. ylic acids. They reported the selective recognition of different
These 1,2-diols can be utilized as synthons for the synthesis dicarboxylic acids through multipoint hydrogen bonds.
of biologically important compounds such as HIV protease in- Thus FriedeleCrafts acylation of 61 produced diketone 62.
hibitors and natural products. Diketone 62 on treatment with POCl3/DMF afforded 4,40 -bis-
(1-chloro-2-formylethenyl)-phenylmethane 63. Bis-chloroal-
dehyde on condensation with methyl thioglycolate/Et3N in
pyridine followed by ring closure with 50% KOH solution
Table 1 produced the bis-thiophene-5-carboxylic ester derivative 64.
Pinacol coupling reaction of a,b-unsaturated aldehyde
Subsequent hydrolysis with aq ethanolic KOH afforded bis-
Entry R1 R2 R3 Temp ( C) Time Yield carboxylic acid 65. Reaction of this bis-acid with oxalyl
(h)
(%)a dl/mesob chloride formed the bis-acid chloride derivative, which on
1: a Ph H H From 78 to 20 2.5 83 >99:1 treatment with 2-aminopyridine resulted in the formation of
2: b Ph H Cl From 78 to 70 0.5 87 >99:1 the receptor 67. The reaction of the bis-acid chloride with
3: c Ph H Br From 78 to 50 1.5 85 >99:1 o-anisidine under identical condition furnished another
4: d Ph H I From 78 to 20 4.0 88 >99:1
5: e Ph Br H From 78 to 0 6.5 68 >99:1
receptor 66.
6: f n-Pr H H From 78 to 10 3.5 16 >99:1
7: g n-Pr H Br From 78 to 20 2.5 82 >99:1 3.11. Synthesis of aromatics
8: h n-Pr H I From 78 to 0 5.0 72 >99:1
9: I t-Bu H H From 78 to rt 20 0 0
10: j t-Bu H Cl From 78 to rt 10 57 93:7 Cho’s group28 showed that b-bromovinyl aldehydes 69, ob-
11: k e(CH2)4e H From 78 to rt 24 0 0 tained from ketone 68, undergo an aromatization with various
12: l e(CH2)4e Cl From 78 to rt 22.5 32 97:3 suitably electron-withdrawing group-substituted alkenes in the
a
Isolated yield. presence of a palladium catalyst and a base via domino Heck
b
Determined by 1H NMR. and aldol processes (Scheme 14). This reaction will operate as
 S. Brahma, J.K. Ray / Tetrahedron 64 (2008) 2883e2896 2889

acetyl chloride X
X
anhyd. AlCl3/CS2 Me Me
83%
O 62 O
X = S, O, CH2
61 86% POCl3/DMF

X .methyl thioglycolate
triethylamine X
pyridine
Cl Cl
69%
S S
64 OHC CHO
MeO2C CO2Me 63

51% KOH, ethanol

X
X
oxalyl chloride
dry DMF (cat) S S
S S DCM ClOC COCl
HOOC 65 COOH
o-anisidine 2-aminopyridine
triethylamine 16% triethylamine
DCM DCM
15%
X X

S S S S
O C C O O C C O
NH HN NH HN

OMe N N
MeO 67
66

Scheme 13. Synthesis of ditopic receptors.

a useful procedure for the synthesis of aromatics 70 from Br

Br In/allyl bromide
ketones. Pd(OAc)2/PPh3
DMF, 0 °C HCOONa
CHO
72 H OH DMF
71 73 O
3.12. Synthesis of cyclopentanone-containing fused rings
Scheme 15.

Ray’s group29,30 has outlined a palladium-catalyzed cyclo-

isomerization toward the synthesis of fused carbocycles 73 and
75 (Schemes 15 and 16) starting from bromovinyl aldehyde
71. The developed methodology serves as an effective transi- Br In/propargyl bromide
Br
Pd(OAc)2/PPh3
tion metal-catalyzed protocol for the cyclization of unactivated DMF, 0 °C
CHO HCOONa
alkenes 72 and alkynes 74 to functionalized ketones via a tan- 74 H OH DMF
71 75 O
dem process. Cyclopentanone-containing 5,5-, 6,5-, 7,5-, and
8,5-fused rings were prepared by using this methodology. Scheme 16.

CHO E1
PBr3/DMF/CHCl3 [Pd]
E1
O Br E2
69 E2 70
68
E1 = CO2Me, CO2Et, COMe, COPh; E2 = CO2Me, CO2Et

CHO CO2Me CO2Me CHO

[Pd] cat. CO2Me
+ +
CO2Me
Br CO2Me CO2Me

Scheme 14.
2890 S. Brahma, J.K. Ray / Tetrahedron 64 (2008) 2883e2896

3.13. Synthesis of azirines and isooxazoles X

CHO
X
CHO X
O
R1 R1 N
R1 CH2Cl2
Cl NaN3 N3
Ray and Brahma31 have also developed a simple and useful reflux
DMSO R2 R4
method for the synthesis of azirines containing an aldehyde R2 R4 R2 R4
R3 R3
functionality, from open-chain bromo/chloroaldehydes at R3
85 86
room temperature. In this synthesis, the acyclic bromo/chlor- 84
oaldehydes 76 were reacted with sodium azide in DMSO at
a) R1 = R2 = R3 = R4 =H, X = CH2
10  C to give the corresponding non-isolable 3-azidoaldehydes
77, which at room temperature, underwent spontaneous deni- b) R1, R2, = -CH=CH-CH=CH-, R3 = R4 = H, X = CH2
trogenation and ring closure to 2-formyl-azirines 78 as the ma- c) R1 = R2 = H, R3, R4 = -CH=CH-CH=CH-, X = O
jor products via the corresponding vinyl nitrenes (Scheme 17).
Scheme 19.

R1 R1
R1 X/ N3 R1 N
NaN3/DMSO rt, 5 min
N + O
the preparation of 2-substituted quindolines 88 starting from
10 °C, 15 min
R2 CHO R2
the chloroaldehyde of 2-nitroacetophenone 89 (Scheme 20).
R2 CHO R2 CHO
76 77 78 79 When 2-nitroacetophenone was treated with POCl3 in DMF,
R1 = Ph, 2-naphthyl, p-MeC6H4; R2 = Ph, H; X/ = Br, Cl it underwent a VilsmeiereHaack reaction to produce b-chloro-
cinnamaldehyde 90, with the nitro group remaining intact.
Scheme 17.
Chloroaldehyde upon reaction with 2.2 equiv of aniline in
2 N ethanolic HCl at 0  C produced the corresponding
Bis-bromo/chloroaldehydes 80 also underwent this reaction
enaminoimine hydrochloride 91 in very good yield. Thermal
in an analogous fashion, i.e., giving mainly 2H-azirines 82
cyclization of this compound at 200e300  C produced 2-(2-
with minor amounts of isooxazoles 83 (Scheme 18) via non-
nitrophenyl)quindoline 92 (R¼H) as a major isolable product.
isolable bis-azidoaldehyde intermediate 81. On the other
The desired quinoline 93 (R¼H) was synthesized by heating
hand, the fused-system azidoaldehydes 85, obtained from 84,
2-(2-nitrophenyl)quindoline with triethyl phosphate at 160  C.
on thermolysis resulted in only the isooxazoles 86 (Scheme
Ray et al. also synthesized various 2-substituted quinolines
19). Here, they isolated azidoaldehyde intermediate4 85.
93 following this procedure.

3.14. Synthesis of various 2-substituted cryptolepines 3.15. Synthesis of substituted benzene by homo/hetero-
coupling of halovinyl aldehydes
Cryptolepine 87a is an important indoloquinoline alkaloid
found in Cryptolepis sanguinolenta, a shrub used in traditional Different substituted benzene derivatives can be obtained
medicine for the treatment of malaria as well as a number of from homo- and hetero-coupling of bromovinyl aldehydes fol-
other diseases in Central and West Africa. lowed by McMurry coupling.
In order to develop a general method for the synthesis of Ray et al.33 have developed a convenient synthetic ap-
various 2-substituted cryptolepines, Ray et al.32 undertook proach to substituted benzene derivatives by modified Ull-
Me mann cross-coupling of bromovinyl aldehydes followed by
7 6 7 6
8 N5
4 5
N
4 intramolecular McMurry coupling. Thus, when keto methyl-
3 8 3
9 9
ene compounds 94 were treated with PBr3 in DMF, bromo-
N
11
2 R N10 2 R vinyl aldehydes 95 were produced, which, upon treatment
10 1 H 11 1
87a (R = H), 87b (R = Me) with an equivalent of Cu powder and 10 mol % of Pd(PPh3)4
88a (R = H), 88b (R = Me)
87c (R = Br), 87d (R = I)
88c (R = Br), 88d (R = I) in anhydrous DMSO with heating at 110  C, afforded the

X X
X/ X/ NaN3/DMSO N3 N3
10 °C, 15 min
OHC 80 CHO OHC 81 CHO

X = O, S, CH2 ;
X/ = Br, Cl rt, 5 min

X X

H + N N
H O
O
OHC N N CHO 83
82

Scheme 18.
 S. Brahma, J.K. Ray / Tetrahedron 64 (2008) 2883e2896 2891

NO2 NO2
NO2
POCl3 Cl 2 Nethanolic HCl NH R
.HCl
Me DMF arylamine
H CHO 91 H CH N R
89 O 90

200-300 °C

N NO2
BaO, KOH P(OEt)3
cryptolepines N
acetone reflux
reflux N R
H
R
R = H, CH3, Br, I R = H, CH3, Br, I
93 92

Scheme 20.

homo-bis-aldehydes 96 (Scheme 21) by a modified Ullmann
reaction.7
When two different bromovinyl aldehydes 97 and 98 were
reacted, only the cross-coupled bis-aldehydes 99 were isolated
under similar conditions to the homo-coupling reaction at
85  C (Scheme 22). Raising the temperature from 85 to
110  C led to a mixture of homo- and hetero-coupled bis-alde-
hydes. Thus, these workers had determined the optimum tem-
perature for preparing the cross-coupled products.
These bis-aldehydes 96 and 99 upon treatment with TiCl4
and Zn dust underwent intramolecular McMurry coupling to
generate the substituted benzenes 100 and 101 (Scheme 23).
Ray et al. have therefore developed a convenient methodol-
ogy for the synthesis of various substituted benzenes starting
from keto methylene compounds. Their method provides short
reaction times and good yields.
3.16. Synthesis of lactones
Cho’s group34 demonstrated that b-bromovinyl aldehydes
103, obtained from the corresponding ketone 102, undergo
an unusual carbonylative cyclization under carbon monoxide
pressure in the presence of a palladium catalyst and a base to af-
ford the corresponding lactones 104 in high yield (Scheme 24).

CHO [Pd], CO
O Br PBr3/DMF/CHCl3
O
PBr3 Cu
O Br O
DMF CHO
Pd(PPh3)4
CHO CHO 102 103 104
95 dry DMSO
94
Δ 96
homo-coupling CHO cat. [Pd], CO
O
Scheme 21. MeCN, 100 °C, 3 h
Br
O

Scheme 24.
n
Br Br n Cu
+ Pd(PPh3)4 3.17. Synthesis of substituted pyrazoles
CHO OHC dry DMSO CHO CHO
85 °C
97 98 99 Cho and Patel35 have described that cyclic and acyclic b-
n = 1-3 n = 1-3 bromovinyl aldehydes 106, derived from appropriate ketone
hetero-coupling
105, are cyclized with an array of arylhydrazines in toluene
Scheme 22. at 125  C in the presence of a palladium catalyst and a phospho-
rus chelating ligand together with NaOtBu to give 1-aryl-1H-
pyrazoles 107 in moderate-to-good yield via an intrinsic CeN
Zn, TiCl4 bond formation (Scheme 1). The present reaction is a new
dry THF
80 °C
route for the synthesis of pyrazoles from ketones (Scheme 25).
CHO CHO
96 100 CHO [Pd] H N-NH-Ar
PBr3/DMF/CHCl3 2
N
Zn, TiCl4 O Br Ar = Ph N
n dry THF n Ar
105 106
107
80 °C
CHO CHO CHO cat. [Pd]
101 + H2N-NH-Ph N
99 NaOtBu
Br N
n = 1-3 n = 1-3 Ph

Scheme 23. Scheme 25.

2892 S. Brahma, J.K. Ray / Tetrahedron 64 (2008) 2883e2896

3.18. Synthesis of 1,2-disubstituted arylnaphthalenes R1

R2 O R2 Br R2
i ii
de Koning et al.36 have developed a methodology for the NR4
R3 R3 CHO R3
synthesis of 1,2-disubstituted arylnaphthalenes from a-tetra-
114 115 116 H
lones. In this synthesis, a-tetralones such as 108 were initially
converted into 1-bromo-dihydronaphthalene-2-carbaldehydes Scheme 27. Reagents and conditions: (i) PBr3/DMF/CHCl3; (ii) R1CCH/
and 1-bromo-naphthalene-2-carbaldehydes 109a,b. These pre- (PPh3)2PdCl2/CuI/Et3N/THF.
cursors were then subjected to Suzuki coupling reactions to
afford 1,2-disubstituted aryldihydronaphthalenes and 1,2- OMe O
disubstituted arylnaphthalenes 110a,b, respectively. Reduction R1 R1 Me R1
Cr(CO)5 Me
with sodium borohydride afforded alcohols 111a,b. It was R2 R2 R2
HCl
converted to acetate derivatives 112a,b by treating with Me OMe
NR4 N R4 N R4
R3 THF, 60 °C
Ac2O in pyridine. The former products were oxidized with R3 R3
H 117 118
DDQ to give 1,2-disubstituted arylnaphthalenes 113 (Scheme 116
26).
Scheme 28.

3.19. Synthesis of alkenylpyrrole derivatives

Table 2
Herndon and Zhang37 have described that alkenylpyrrole Synthesis of pyrroles 118 through coupling of enyne-imines with Fischer car-
derivatives can be prepared from the coupling of enyne-imines bene complexes
with Fischer carbene complexes. Here, enyne-imines 116 were Entry R1 R2 R3 R4 Yield 118 (%)
synthesized from the corresponding bromoaldehydes 115 A Bu Ph H NMe2 62
(Scheme 27), which were prepared from 114. B Bu Ph H Ts 37
A variety of imines 116 were treated with a chromium car- C Bu Ph H Ms 35
D Bu Ph H CH2Ph 9
bene complex to produce the alkenylpyrrole derivatives 117 E Bu Bu H NMe2 64
(Scheme 28). The initially formed enol ether-pyrrole deriva- F H Bu H NMe2 59
tives 117 were unstable with respect to air oxidation and G Bu H H NMe2 70
were hydrolyzed to the corresponding ketones 118 for charac- H Bu H Et NMe2 74
terization purposes. Results are shown in Table 2. I Bu H Allyl NMe2 64
J Bu e(CH2)4e NMe2 36
K Bu e(CH2)3e NMe2 25

3.20. Stereoselective synthesis of taxol C-ring

Nakada et al. have achieved the highly stereoselective con-
struction of the C3 stereogenic center of the taxol C-ring.38
The trans isomer at the C3eC8 position of the taxol C-ring,
which is required for the total synthesis of taxol, as well as
its cis isomer, was successfully synthesized by the diastereo-
selective SN20 reduction of allylic phosphonium salts. The
reaction commenced with the bromoaldehyde obtained from
the enantiopure ketol (Scheme 29).
This is the first diastereoselective SN20 reduction of an al-
lylic phosphonium salt, which constructs a stereogenic tertiary
carbon center with high selectivity. This protocol would be ap-
plicable for other cyclic systems as well as for acyclic systems
to generate a new stereogenic center.

B(OH)2

R R R
i R
CHO ii CHO
R R R
O Br Ar
108 109a,b 110a,b
R=H Ar = Ph, 2-MePh, Naphthyl, 3,4,5-(MeO)C6H2
R = OMe
R R R
iii iv v
OH OAc OAc
R R R
Ar Ar Ar
111a,b 112a,b 113
a = dihydronaphthalene
b = naphthalene

Scheme 26. Reagents and conditions: (i) DMF, PBr3, CH2Cl2, reflux, R¼H, 70%; R¼OMe, 63%; (ii) cat. Pd(PPh3)4, aq Na2CO3, boronic acid, DME/EtOH, reflux;
(iii) NaBH4, EtOH, rt; (iv) Ac2O, pyridine, reflux; (v) DDQ, CH2Cl2, reflux.
 S. Brahma, J.K. Ray / Tetrahedron 64 (2008) 2883e2896 2893

1-encarbaldehyde 121 was treated with ethyl acetoacetate and

potassium carbonate in a solvent system containing DMF and
water (1:1), compound 122 was unexpectedly obtained in 52%
yield (Scheme 31).

CO2Et
Br
K2CO3
CHO + MeCOCH2CO2Et
DMF:H2O (1:1), rt.
121 122

Scheme 31.

3.22. Synthesis of cuparenone

A large number of multistep methods have been developed

for the synthesis of cuparenone, herbetenone, etc., where
the synthetic approaches are lengthy and hazardous. In this
context, Ray’s group40 highlighted the formation of a gem-
dimethylcyclopentenone moiety from 1-bromo-5-methyl-1-
aryl-hexa-1,5-dien-3-ols 123 obtained from the corresponding
bromoaldehydes using palladium-catalyzed Heck reaction
conditions.
They utilized the method in obtaining two different prod-
ucts 124 and 125 from a common starting material by varying
the reaction conditions (Scheme 32).
The retrosynthetic pathway for the formation of the com-
pounds is as follows (Scheme 33).
When the precursors were subjected to Heck reaction con-
ditions in the presence of bases other than sodium formate,
gem-dimethylcyclopentenone derivatives were obtained
(Scheme 34). The reaction was then attempted by changing
Scheme 29. the base, solvent, and catalyst to optimize the reaction
conditions.
This methodology has the potential to be of great benefit in
the convergent synthesis of a number of natural product
3.21. Synthetic approach toward substituted benzene moieties.
derivatives
3.23. Synthesis of various quinolines
Ray and Ray39 developed a simple, convenient, one-pot
synthetic approach toward the substituted benzene derivatives Recently, Ray’s group has developed two short, distinct,
120 using base catalyzed condensation of b-bromovinyl alde- and complementary methods for the synthesis of various
hydes 119 with b-ketoesters followed by water-mediated cy- 3,4-annulated and 4-substituted quinolines from b-bromo-
clization and aromatization (Scheme 30). a,b-unsaturated aldehydes (127) and either 1-bromo-2-nitro-
benzene (128, X¼Br) or 2-bromoacetanilide.
R These involved subjecting certain enolizable (and often cy-
Br Me clic) ketones 126 to a VilsmeiereHaack haloformylation reac-
+ RCH2R' K2CO3, DMF
tion and then engaging the resulting b-bromo-a,b-unsaturated
CHO H2O, 28 °C R'
119 120
aldehydes 127 in a Pd(0)-mediated Ullmann cross-coupling re-
R = COMe
action with 1-bromo- or 1-iodo-2-nitrobenzene 128 to generate
R' = CO2Et, CO2Me, COMe
the corresponding b-(o-nitrophenyl)-a,b-unsaturated alde-
Scheme 30. hydes 129. Subjection of this last type of compound to reduc-
tive cyclization using dihydrogen in the presence of 10% Pd
They performed the reaction in various solvents and found on C or a large excess of TiCl3 then gave the target quinolines
varying percentages of yields. During their trial for the estab- 130 (Scheme 35).41
lishment of this methodology, they obtained an interesting New protocols for the reductive cyclization of compounds
result by varying the solvent system. When 2-bromo-cyclopent- of the general form 129 have been identified and these should
2894 S. Brahma, J.K. Ray / Tetrahedron 64 (2008) 2883e2896

Scheme 32.

prove broadly applicable to the preparation of quinolines bear-

R1 R1 O R1
O ing a range of different functional groups.

R2
3.24. Synthesis of polycyclic quinolines
R2 R2
Br
R1
Br R1 CHO Recently, Ray and Some42 have reported a simple, two-step
OH procedure for the facile synthesis of polycyclic quinolines 135,
+ Br
R2
which involves selective Pd-catalyzed arylamination of b-bro-
R2
movinyl aldehydes 131 by substituted aromatic amines 132
Scheme 33. followed by acid-catalyzed cyclization with trifluoroacetic

Br R1
R1 R1 OH R1
O
OH OH

R2 R2 R2
R2

Scheme 34.

O CHO X
POBr3
+ acid (Scheme 36). Compounds 133 and 134 were formed as
DMF
Br O2N intermediates. Thus two-step methodology for the synthesis
126 127 128
X = Br, I of various polycyclic quinolines required short reaction times
Cu, DMSO Pd[0] (10 mol%) and gave improved yields of products (Scheme 36). Results for
Δ
CHO
the formation of 133 and 134 are shown in Table 3.
H2
10% Pd on C 4. Conclusions
N
130 O2N
129 In conclusion, it is clear that halovinyl aldehydes have al-
Scheme 35. ready found a unique position in organic chemistry in view

R2 R1
R H R
Br H2N N Br
Pd2(dba)3, K2CO3
+ +
(R)-(+)- BINAP N R
CHO R1 toluene CHO R1
R2 90 °C, 3 h 133 R2 134
131
132 TFA, 10-12 h

R
N

R1
R2
135

Scheme 36.
 S. Brahma, J.K. Ray / Tetrahedron 64 (2008) 2883e2896 2895

Table 3 6. Kar, G. K.; Karmakar, A. C.; Ray, J. K. Tetrahedron Lett. 1989,

Reaction of 131 with various substituted anilines 30, 223.
Br 7. Grief, D.; Kropfgans, F.; Pulst, M.; Weibenfels, M. Synthesis 1989, 515.
CHO 8. Sami, I.; Kar, G. K.; Ray, J. K. Tetrahedron 1992, 42, 5199.
9. Racci, A.; Balucani, D.; Fravolini, A.; Schiaffella, F.; Grandolini, G. Gazz.
Chim. Ital. 1977, 107, 19.
136 10. Aubert, T.; Tabyaoui, B.; Farnier, M.; Guilard, R. Synthesis 1988, 742.
11. Kar, G. K.; Karmakar, A. C.; Ray, J. K. J. Heterocycl. Chem. 1991, 28,
Entry R R1 R2 Yield (% of 133) Yield (% of 134) 999.
12. Coates, R. M.; Muskopf, J. W.; Senter, P. A. J. Org. Chem. 1985,
1 H OMe H 80 18
50, 3541.
2 Me H Me 50 30
13. Kar, G. K.; Karmakar, A. C.; Makur, A.; Ray, J. K. Heterocycles 1995, 41,
3 OMe H H 70 18
911.
4 Me H H 45 24
14. Ray, J. K.; Kar, G. K.; Haldar, M. K. Synth. Commun. 1996, 26, 3959.
5 OMe H OMe 95 0
15. Kar, G. K.; Sami, I.; Ray, J. K. Chem. Lett. 1992, 1739.
6 OH H H 14 5
16. Kar, G. K.; Haldar, M. K.; Gupta, S.; Pan, D.; Ray, J. K. J. Indian Chem.
7 H OH H 20 8
Soc. 1999, 76, 569.
8 NO2 H H 10 2
17. Gilchrist, T. L.; Healy, M. A. M. Tetrahedron 1993, 49, 2543.
Bromovinyl aldehyde 136 (1 mmol), amine (1 mmol), Pd2(dba)3 (3 mol %), 18. Haldar, M. K.; Kar, G. K.; Ray, J. K. Synlett 1997, 1057.
K2CO3 (1.4 mmol), and (R)-(þ)-BINAP (4 mol %) at 90  C for 3e4 h under 19. Harvey, R. G. Polycyclic Aromatic Hydrocarbons, Chemistry and Carcino-
an argon atmosphere. genicity; Cambridge University Press: Cambridge, 1991.
20. Zajc, B. J. Org. Chem. 1999, 64, 1902.
21. Pan, D.; Kar, G. K.; Ray, J. K.; Lin, J.-M.; Amin, S.; Chantrapromma, S.;
of their use in synthesizing organic compounds of different Fun, H.-K. J. Chem. Soc., Perkin Trans. 1 2001, 2470.
types. Ever since the discovery of the halovinyl aldehydes, 22. Kanomata, N.; Nakata, T. Heterocycles 1998, 48, 2551.
the chemical world has witnessed a remarkable progress in 23. Gevorgyan, V.; Quan, L. G.; Yamamoto, Y. Tetrahedron Lett. 1999, 40,
their use as synthetic tools for various organic syntheses. 4089.
24. Ray, J. K.; Haldar, M. K.; Gupta, S.; Kar, G. K. Tetrahedron 2000, 56, 909.
Many new methodologies are continuously developing in
25. Shimizu, M.; Goto, H.; Hayakawa, R. Org. Lett. 2002, 4097.
this field and our laboratory is contributing to those. New 26. Ray, J. K.; Gupta, S.; Pan, D. Tetrahedron 2001, 57, 7213.
and interesting achievements in halovinyl aldehyde chemistry 27. Brahma, S.; Pan, D.; Ray, J. K. Supramol. Chem. 2004, 16, 447.
can be expected in the near future. 28. Cho, C. S.; Patel, D. B.; Shim, S. C. Tetrahedron 2005, 61, 9490.
29. Mal, S. K.; Ray, D.; Ray, J. K. Tetrahedron Lett. 2004, 45, 277.
Acknowledgements 30. Ray, D.; Mal, S. K.; Ray, J. K. Synlett 2005, 2135.
31. Brahma, S.; Ray, J. K. Tetrahedron Lett. 2005, 46, 6575.
32. Dutta, B.; Some, S.; Ray, J. K. Tetrahedron Lett. 2006, 47, 377.
We thank the DRDO, the DST, the CSIR (New Delhi), and 33. Some, S.; Dutta, B.; Ray, J. K. Tetrahedron Lett. 2006, 47, 1221.
the Indian Institute of Technology for financial assistance. 34. Cho, C. S.; Shim, H. S. Tetrahedron Lett. 2006, 47, 3835.
35. Cho, C. S.; Patel, D. B. Tetrahedron Lett. 2006, 62, 6388.
36. Moleele, S. S.; Michael, J. P.; de Koning, C. B. Tetrahedron 2006, 62,
References and notes 2831.
37. Zhang, Y.; Herndon, J. W. Org. Lett. 2003, 2043.
1. Vilsmeier, A.; Haack, A. Ber. Dtsch. Chem. Ges. 1927, 60, 119. 38. Utsugi, M.; Miyano, M.; Nakada, M. Org. Lett. 2006, 2973.
2. Arnold, Z.; Zemlicka, J. Proc. Chem. Soc., London 1958, 227. 39. Ray, D.; Ray, J. K. Tetrahedron Lett. 2007, 48, 673.
3. Arnold, Z.; Holy, A. Collect. Czech. Chem. Commun. 1961, 26, 3059. 40. Ray, D.; Ray, J. K. Org. Lett. 2007, 1617.
4. Sami, I.; Kar, G. K.; Ray, J. K. Org. Prep. Proced. Int. 1991, 23, 186. 41. Some, S.; Ray, J. K.; Banwell, M. G.; Jones, M. T. Tetrahedron Lett. 2007,
5. Aubert, T.; Tabyaoui, B.; Farnier, M.; Guilard, R. J. Chem. Soc., Perkin 48, 3609.
Trans. 1 1989, 1369. 42. Some, S.; Ray, J. K. Tetrahedron Lett. 2007, 48, 5013.
2896 S. Brahma, J.K. Ray / Tetrahedron 64 (2008) 2883e2896

Biographical sketch

Sulagna Brahma was born in Paschim Midnapur, India in 1977. She received
her M.Sc. (Chemistry) degree in 2000, from Vidyasagar University, India. She
earned her Ph.D. in 2006 under the supervision of Prof. Jayanta K. Ray at In-
dian Institute of Technology, Kharagpur, India. She received ‘Young Scientist’
award of the Indian Chemical Society in 2003. Her research interests include
molecular recognition, hosteguest interactions, and synthesis of new recep-
tors. Presently, she is working as a visiting scholar at University of Nebraska
Lincoln (USA) under the guidance of Prof. Andrzej Rajca.
Dr. Jayanta K. Ray was born in Kharagpur, India. He did his Ph.D. under the
supervision of Prof. U. R. Ghatak at Indian Association for the Cultivation of
Science, Kolkata, India. He did his postdoctoral works with Prof. R. G. Harvey
at University of Chicago and with Prof. F. A. Davis at Drexel University, USA.
He is a Faculty member of Department of Chemistry, Indian Institute of Tech-
nology, Kharagpur, since 1977. He was Head of the Department during 2002e
2005. His research interest is on development of methodologies and total syn-
thesis of natural products.