β-acylvinyl anion and dianion equivalents: Lithiation of 1-[(2EZ)-3-chloroprop-2-enyl]-1H-1,2,3-benzotriazole: Preparation and elaboration of 1-(2-oxiranylvinyl)-1H-benzotriazoles

Article abstract of DOI:10.1021/jo049818j

The allyllithium generated from 1-[(2EZ)-3-chloroprop-2-enyl]-1H-1,2,3- benzotriazole (5) and LDA, in the presence of HMPA, reacts with enolizable and nonenolizable carbonyls solely at the CCl terminus to give 1-(2-oxiranylvinyl) benzotriazoles 6a-g in 61

Full text of DOI:10.1021/jo049818j

â-Acylvin yl An ion a n d Dia n ion Equ iva len ts: Lith ia tion of
1-[(2EZ)-3-Ch lor op r op -2-en yl]-1H-1,2,3-ben zotr ia zole: P r ep a r a tion
a n d Ela bor a tion of 1-(2-Oxir a n ylvin yl)-1H-ben zotr ia zoles
Alan R. Katritzky,*,‡ Kavita Manju,‡ Anna V. Gromova,‡ and Peter J . Steel§
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200, and Department of Chemistry, University of Canterbury,
Christchurch, New Zealand
katritzky@chem.ufl.edu
Received J anuary 31, 2004
The allyllithium generated from 1-[(2EZ)-3-chloroprop-2-enyl]-1H-1,2,3-benzotriazole (5) and LDA,
in the presence of HMPA, reacts with enolizable and nonenolizable carbonyls solely at the CCl
terminus to give 1-(2-oxiranylvinyl)benzotriazoles 6a -g in 61-82% yields. Allyllithiums generated
from 6a ,c reacted exclusively at the CBt terminus to give 10a -d in 68-88% yields. Acidic hydrolysis
of (oxiranylvinyl)benzotriazoles 6a -g and 10a -d provided 4-hydroxyalk-2-en-1-one derivatives
12a ,b,c,e,g, 13a -d , and furan 14 in 54-86% yields.
SCHEME 1
In tr od u ction
Regiocontrol in the deprotonation-substitution of un-
symmetrically substituted allylic systems is challenging.
Heteroatom-stabilized allylic anions of type 1 are syn-
thetically important as 3-carbon homologating agents.1
Species 1 can act as diverse reversed-polarity equiva-
lents: homoenolate anions 2,2 â-acylvinyl anions 3,3 or
R,â-unsaturated acyl anions 44a-c (Scheme 1). The R/γ-
regiochemistry of ambident allylic anions is controlled
in a complex manner by several factors, such as the
nature of the heteroatom(s), charge delocalization, steric
effects, countercation, type of electrophile, solvation, and
additives.5 Allylic anions stabilized by a wide variety of
heteroatoms including oxygen, sulfur, selenium, nitrogen,
phosphorus, boron, silicon, and halogens have been
examined.6
Prior to the advent of the in situ quench procedure
(Barbier technique),7 1-chloroallyllithiums were underuti-
‡ University of Florida.
§ University of Canterbury.
(1) Stowell, J . C. Chem. Rev. 1984, 84, 409.
(2) Ahlbrecht, H.; Beyer, U. Synthesis 1999, 365.
(3) (a) Chinchilla, R.; Na´jera, C. Chem. Rev. 2000, 100, 1891. (b)
Bachki, A.; Foubelo, F.; Yus, M. Tetrahedron 1997, 53, 4921. (c) Meyers,
A. I.; Spohn, R. F. J . Org. Chem. 1985, 50, 4872. (d) Shih, C.; Swenton,
J . S. J . Org. Chem. 1982, 47, 2825. (e) Parrain, J .-L.; Beaudet, I.;
Ducheˆne, A.; Watrelot, S.; Quintard, J .-P. Tetrahedron Lett. 1993, 34,
5445. (f) Parrain, J .-L.; Ducheˆne, A.; Quintard, J .-P. J . Chem. Soc.,
Perkin Trans. 1 1990, 187. (g) Sato, T.; Otera, J .; Nozaki, H. J . Org.
Chem. 1989, 54, 2779. (h) Corey, E. J .; Erickson, B. W.; Noyori, R. J .
Am. Chem. Soc. 1971, 93, 1724. (i) Reich, H. J .; Clark, M. C.; Willis,
W. W., J r. J . Org. Chem. 1982, 47, 1618. (j) Craig, D.; Etheridge, C.
J .; Smith, A. M. Tetrahedron 1996, 52, 15267. (k) J in, Z.; Fuchs, P. L.
J . Am. Chem. Soc. 1994, 116, 5995. (l) Funk, R. L.; Bolton, G. L. J .
Am. Chem. Soc. 1988, 110, 1290.
(4) (a) Ito, H.; Taguchi, T. Tetrahedron Lett. 1997, 38, 5829. (b)
Katritzky, A. R.; Zhang, G.; J iang, J . J . Org. Chem. 1995, 60, 7589. (c)
J acobson, R. M.; Lahm, G. P.; Clader, J . W. J . Org. Chem. 1980, 45,
395.
(5) Yamamoto, Y. In Comprehensive Organic Synthesis; Trost, B.
M., Fleming, I., Eds.; Pergamon Press: New York, 1991; Vol. 2, p 55.
(6) Katritzky, A. R.; Piffl, M.; Lang, H.; Anders, E. Chem. Rev. 1999,
99, 665.
lized because of facile self-coupling. 1-Chloroallyllithiums
preferentially react at the CH2 terminus with carbonyl
compounds and at the CCl terminus with aliphatic
halides.8a-c However, replacement of the lithium coun-
terion with zinc results in a regioselective reaction at the
CCl terminus with aldehydes as electrophiles.9 Chloro-
allyllithiums generated from trans-cinnamyl chloride and
2-[(1E)-3-chloroprop-1-enyl]-1,3-benzothiazole react with
(7) Macdonald, T. L.; Narayanan, B. A.; O’Dell, D. E. J . Org. Chem.
1981, 46, 1504.
(8) (a) J ulia, M.; Verpeaux, J .-N.; Zahneisen, T. Bull. Soc. Chim.
Fr. 1994, 131, 539. (b) Mauze`, B.; Ongoka, P.; Miginiac, L. J .
Organomet. Chem. 1984, 264, 1. (c) Doucoure, A.; Mauze`, B.; Miginiac,
L. J . Organomet. Chem. 1982, 236, 139.
(9) Mallaiah, K.; Satyanarayana, J .; Ila, H.; J unjappa, H. Tetrahe-
dron Lett. 1993, 34, 3145.
10.1021/jo049818j CCC: $27.50 © 2004 American Chemical Society
Published on Web 08/05/2004
6018
J . Org. Chem. 2004, 69, 6018-6023

â-Acylvinyl Anion and Dianion Equivalents
SCHEME 2
nonenolizable ketones and aromatic aldehydes at the CCl
terminus exclusively.10
The regioselectivity of additions of 1,1-dichloroallyl-
lithium to carbonyl compounds has been suggested to
depend on electronic factors. Carbonyl compounds with
electron-withdrawing substituents usually favor bond
formation at the CH2 terminus, and those with electron-
releasing groups favor bond formation at the CCl2
terminus.11 The attack could be directed to the CCl2
terminus exclusively by the presence of additives such
t
as BuOK12 or cryptand[2.2.1].13
1-Chloro-(1-trimethylsilyl)allyllithium is less selective
as compared to 1,1-dichloroallyllithium, and both R- and
γ-adducts result from reactions with carbonyl com-
pounds.14 The anion derived from (E)-3-chloro-1-phenyl-
sulfonylprop-1-ene reacts with aldehydes exclusively at
the CCl terminus.15 Both (E)- and (Z)-γ-chloroallylphos-
phonamides react exclusively at the CCl terminus with
R,â-unsaturated ketones to give the corresponding cyclo-
propanes.16
The synthetic utility of allyllithiums generated from
1-allylbenzotriazole,17a,b 1-(1-ethoxyprop-2-enyl)-1H-1,2,3-
benzotriazole,18 3-(benzotriazol-1-yl)-1-ethoxyprop-1-ene,19
and 1-(3-morpholinoprop-2-enyl)benzotriazole20 is well
established. Anions generated from these N-allylbenzo-
triazoles react exclusively at the CBt terminus with
aldehydes and nonhindered ketones. However, the re-
giochemistry is reversed to give γ-adducts when the
intermediate 1-(benzotriazol-1-yl)-3-(diphenylphospho-
ryl)-1-ethoxyprop-1-ene is first generated in situ from
1-(1-ethoxyprop-2-enyl)-1H-1,2,3-benzotriazole; deproto-
nation of the phosphoryl intermediate and subsequent
reaction with carbonyl compounds now result in hydroxy-
alkylation exclusively at the CP terminus.21
We now report regiospecific lithiation-substitutions of
1-[(2EZ)-3-chloroprop-2-enyl]-1H-1,2,3-benzotriazole and
its utilization as â-acylvinyl anion (-CHdCHCHO) or
â-acylvinyl dianion (-COCHdCH-) equivalents.
Resu lts a n d Discu ssion
(10) Florio, S.; Troisi, L. Tetrahedron Lett. 1996, 37, 4777.
(11) Seyferth, D.; Murphy, G. J .; Mauze`, B. J . Am. Chem. Soc. 1977,
99, 5317.
(12) Canepa, C.; Cobianco, S.; Degani, I.; Gatti, A.; Venturello, P.
Tetrahedron 1991, 47, 1485.
(13) Canepa, C.; Prandi, C.; Venturello, P. Tetrahedron 1994, 50,
8161.
(14) Seyferth, D.; Mammarella, R. E. J . Organomet. Chem. 1978,
156, 279.
(15) Gallagher, E. T.; Grayson, D. H. Org. Biomol. Chem. 2003, 1,
1374.
(16) Hanessian, S.; Andreotti, D.; Gomtsyan, A. J . Am. Chem. Soc.
1995, 117, 10393.
Regioselectivity of Rea ction s of Lith ia ted (E)-5
a n d (Z)-5 w ith Ca r bon yl Com p ou n d s. 1-[(2EZ)-3-
Chloroprop-2-enyl]-1H-1,2,3-benzotriazole (5) was pre-
pared by the reaction of BtNa and (1EZ)-1,3-dichloroprop-
1-ene. (Z)-5 (47%) and (E)-5 (21%) were separated by
silica gel column chromatography. Unlike (1E)-3-chloro-
1-phenylsulfonylprop-1-ene,15 no E/ Z-isomerization was
observed when a 1:1 mixture of (E)-5 and (Z)-5 was
stirred with Et3N in CHCl3 at 20 °C for 3 h. Under
Barbier conditions,7 lithiated (E)-5 or (Z)-5 reacted with
various carbonyl compounds at the CBt terminus to give
the corresponding homoallylic alcohols 7b-d or at the
CCl terminus to give either the corresponding (oxiranyl-
vinyl)benzotriazoles 6a ,b or allylic alcohol 8c (Scheme
2).
(17) (a) Katritzky, A. R.; Wang, X.; Denisenko, A. J . Org. Chem.
2001, 66, 2850. (b) 1- or 2-Allylbenzotriazoles are known to isomerize
t
in the presence of tBuOK in BuOH but undergo lithiation-substitution
without isomerization. For details see: Katritzky, A. R.; Li, J .;
Malhotra, N. Liebigs Ann. Chem. 1992, 843. (c) Absence of the
isomerization of the double bond suggests the irreversible nature of
lithiation-substitution. Also, no isomerization of the unreacted starting
material (Z)-5 was detected after reaction with benzaldehyde, ben-
zophenone, or acetophenone as indicated by the 1H NMR spectra of
the crude products.
(18) Katritzky, A. R.; J iang, J . J . Prakt. Chem. Weinheim., Ger. 1999,
341, 79.
(19) Katritzky, A. R.; Wu, H.; Xie, L.; Rachwal, S.; Rachwal, B.;
J iang, J .; Zhang, G.; Lang, H. Synthesis 1995, 1315.
(20) Katritzky, A. R.; Chang, H.-X.; Verin, S. V. Tetrahedron Lett.
1995, 36, 343.
Lithiation of (Z)-5 with LDA at -78 °C and trapping
with benzophenone gave vinyloxirane (E)-6a in 74% yield
as the sole product (Scheme 2). However, reaction of
benzophenone with lithiated (E)-5 provided a complex
mixture of products having both (Z)- and (E)-configured
1
double bonds as shown by the H NMR spectrum.
Deprotonation of (Z)-5 and reaction with acetophenone
at -78 °C gave products from attack at both the CBt and
(21) Katritzky, A. R.; Feng, D.; Lang, H. J . Org. Chem. 1997, 62,
4131.
J . Org. Chem, Vol. 69, No. 18, 2004 6019

Katritzky et al.
SCHEME 3a
the CCl termini in a 1:1 ratio to give (i) vinyloxiranes
trans-(E)-6b and cis-(E)-6b in a combined yield of 28%
in a 2:1 ratio and (ii) homoallylic alcohols (Z)-7b as mixed
diastereomers in 30% yield in a 2:1 ratio. No formation
of the corresponding isomerized alcohol (E)-7b was
1
detected in the H NMR spectrum of the crude product
mixture.17b,c Furthermore, no change in the reaction yield
or the 1:1 product ratio arising from the reaction of
acetophenone at the CBt and the CCl termini was
observed when the reaction was carried out at -30 °C.
Cyclohexanone reacted with the anion generated from
(Z)-5 preferentially at the CBt terminus to give (Z)-7c
in 40% yield; the attack at the CCl terminus now resulted
in allylic alcohol 8c in 10% yield instead of a vinyloxirane.
However, the reaction of cyclohexanone with the anion
from (E)-5 gave the products from the reaction at the
CBt terminus exclusively, with isomerization of the
double bond to give alcohols (E)-7c and (Z)-7c in 20%
and 5% yields, respectively.
Lithiated (Z)-5 and (E)-5 each reacted with benzalde-
hyde only at the CBt terminus to provide the correspond-
ing homoallylic alcohols (Z)-7d and (E)-7d in 68% and
62% yields, respectively. Compounds (Z)-7d and (E)-7d
were each formed as a mixture of syn- and anti-diaster-
eomers in the ratio 2:1. No Z f E isomerization was
1
detected in the H NMR spectrum of the crude material
when (Z)-5 was used as a reactant with benzaldehyde,
but E f Z isomerization was evident (ca. 10% from the
1H NMR spectrum of the crude product mixture). The
syn-stereochemistry of the major isomers of (Z)-7d and
(E)-7d were each unambiguously determined by X-ray
crystallography.
The reaction of lithiated (Z)-5 with hydrocinnamalde-
hyde did not give any of the expected products; only the
corresponding self-coupling product (9) was obtained in
40% yield (Scheme 2).
a
(i) LDA, THF/HMPA (10:1), -78 °C; (ii) LDA, THF/HMPA
(5:1). -78 °C; (iii) n-BuLi, THF, -78 °C, E+; (iv) p-TsOH, THF,
reflux, 30 min. For descriptions of R, R1, and E in 6, 10, 12, and
13, see Tables 1 and 2.
TABLE 1. P r ep a r a tion of γ-Hyd r oxy-r,â-en a ls 12a ,b,c,e,g
via (Oxir a n ylvin yl)ben zotr ia zoles 6a -g
Regiosp ecific Rea ction s of Lith ia ted (EZ)-5 w ith
Ca r bon yl Com p ou n d s in th e P r esen ce of HMP A:
P r ep a r a tion of (Oxir a n ylvin yl)ben zotr ia zoles. Use
of coordinating solvents often results in improved
regioselectivity.22a Indeed, only the products arising from
substitution at the CCl terminus were obtained when the
lithiation-substitution was performed in the presence of
HMPA. Initial experiments with benzaldehyde and p-
chlorobenzophenone conducted in THF/HMPA (ratio 10:
1) resulted in substitution at the CCl terminus only.
However, with benzaldehyde, the oxirane (6d ) and the
alcohol (8d ) were obtained in 32% and 30% yields,
respectively (Scheme 3). Similarly, the reaction with
p-chlorobenzophenone provided 6e and 8e in 40% and
39% yields, respectively. The structure of alcohol 8d was
confirmed by X-ray crystallography. An increase in the
amount of HMPA (THF/HMPA 5:1) resulted in the
formation of oxiranes (E)-6a-g in 61-82% yields (Scheme
3, Table 1). Apparently, HMPA directs the attack of the
electrophile to the CCl terminus and also facilitates ring
closure to give the oxirane.22b
oxirane,
aldehyde,
yielda (%)
entry
R
R1
yielda (%)
1
2
3
4
5
6
7
Ph
Ph
Ph
Me
(CH2)5
H
6a (78)
6b (73)b
6c (72)
6d (69)c
6e (76)d
6f (82)d
6g (61)d
12a (73)
12b (74)
12c (62)
Ph
Ph
Ph
Ph
p-ClPh
p-MeOPh
p-MePh
12e (86)
12g (54)
Isolated yields. b Isolated yield of trans- and cis-isomers is 50%
a
and 23%, respectively. c Isolated yield of trans- and cis-isomers is
d
47% and 22%, respectively. Product is a mixture of isomers in
the ratio 1:1.
and cis-configuration at the oxirane ring and (E)-config-
uration (J trans ∼ 14 Hz) at the double bond in 73% yield.
The major and minor isomers were separated by column
chromatography, and the major isomer was assigned as
trans-(E)-6b by single-crystal X-ray analysis. Similarly,
reaction with benzaldehyde gave a mixture of cis-(E)-6d
(J vic ) 4.1 Hz) and trans-(E)-6d (J vic ) 1.6 Hz) in a 2:1
ratio in 69% yield. Again, the isomers could be separated
by column chromatography. With p-chlorobenzophenone,
p-methoxybenzophenone, and p-methylbenzophenone,
the respective products (E)-6e, (E)-6f, and (E)-6g were
each formed as mixtures of isomers in the ratio 1:1 in
61-82% yield.
The reaction with acetophenone gave an isomeric
mixture of vinyloxirane 6b in the ratio 2:1, with trans-
(22) (a) Still, W. C.; Macdonald, T. L. J . Org. Chem. 1976, 41, 3620.
(b) Apparently, in the presence of HMPA, lithiation-substitution
proceeds in a reversible manner, and formation of the oxirane ring
drives the equilibrium in the forward direction.
6020 J . Org. Chem., Vol. 69, No. 18, 2004

â-Acylvinyl Anion and Dianion Equivalents
SCHEME 5a
TABLE 2. P r ep a r a tion of γ-Hyd r oxy-r,â-en on es 13a -d
via (Oxir a n ylvin yl)ben zotr ia zoles 10a -d
oxirane,
ketone,
entry
R
R1
E
yielda (%)
yielda (%)
1
2
3
4
Ph
Ph
Ph
Ph
Ph
Ph
Me
Et
Bu
Me
10a (88)
10b (72)
10c (68)
10d (85)
13a (76)
13b (78)
13c (82)
13d (56)
(CH2)5
a
Isolated yields.
SCHEME 4a
a
(i) LDA, THF, PhCOPh, -78 °C; (ii) BuLi, MeI, -78 °C; (iii)
LDA, THF, MeI, -78 °C
a
X ) Y ) S, (i) HgCl2; X ) Y ) Se, (i) H2O2; X ) S, Y ) O, (i)
Regiosp ecific Lith ia tion -Su bstitu tion s of (Oxi-
r a n ylvin yl)ben zotr ia zoles. Vinyloxiranes 6a ,c were
further lithiated and reacted with alkyl halides to provide
alkylation exclusively at the CBt terminus. Lithiation of
6a with BuLi and trapping with various alkyl iodides at
-78 °C gave the alkylated products 10a -c in 68-88%
yields (Scheme 3, Table 2). Interestingly, the E-stereo-
chemistry of the double bond is retained, which is evident
from the X-ray structure of 10a and also by J allylic ) 1
Hz between the methyl group and the allylic proton
attached to the oxirane ring. Similarly, lithiation and
subsequent methylation of 6c provided vinyloxirane 10d
in 85% yield. However, the procedure was limited to the
use of alkyl iodides as electrophiles; the use of 3-pen-
tanone to trap lithiated 6a resulted in the oxirane ring
opening to give 11 in 75% yield. The structure for
compound 11 was unambiguously determined by X-ray
crystallography. Thus, both alkyl iodides and carbonyl
compounds react at the CBt terminus of (oxiranylvinyl)-
benzotriazole.
NaIO4 or MoO5; X ) SO2, Y ) O, (i) DBU or SiO2; X ) Y ) O, (i)
150 °C, 72 h; (ii) LDA, R1X, THF, -78 °C; (iii) SiO2, hexane, reflux,
4 h; (iv) BuLi, TMEDA, THF, 0 °C, R2X; (v) NaIO4, dioxane/H2O.
generation of â-acylvinyl anion equivalents involves the
use of protected carbonyl systems 18, which can undergo
halogen3b-d or tin3e,f-lithium exchange (Scheme 5). An
alternative route involves the use of heteroallylic systems
of type 19, which carry the carbonyl group in the
heterovinyl mask.5,6 Deprotonation-electrophilic substitu-
tion followed by unmasking provides an easy introduction
of the â-acylvinyl moiety to the electrophilic reagent. The
thio (X ) Y ) SR and X ) SR, Y ) OR)3g,h,24 and seleno
(X ) Y ) Se)3i analogues of 19 have been used exten-
sively; however, these systems require oxidative unmask-
ing in the presence of reagents such as HgCl2, H2O2,
NaIO4, or MoO5. In the case of allylic sulfones,3j,k often
DBU is required for the final elimination of the sulfonyl
group, and 4H-1,3-dioxin (RX, YR ) -OCH2O- in 19)
requires prolonged thermolysis at 150 °C for 72 h for
deprotection.3l
Although systems of type 19 have been widely utilized
as â-acylvinyl anion equivalents, reports on their use as
â-acylvinyl dianion equivalents are rare. Mandai et al.
introduced R-methoxyallyl sulfides as â-acylvinyl dianion
equivalents; electrophilic substitution (R- to SPh) followed
by silica-gel-promoted thioallylic rearrangement facili-
tated the second electrophilic substitution at the other
end of the allylic system. Furthermore, oxidative removal
of the heteroatoms provided R,â-unsaturated carbonyl
compounds (Scheme 5).24
Starting from (Z)-5, a one-pot, two-step procedure
using the sequence (Z)-5 f [6a ] f 10a gave 10a in 68%
yield (Scheme 4). However, changing the sequence to
(Z)-5 f [16] f 10a resulted in a low yield of 10a (7%)
along with 17 in 62% yield. The regiochemistry of the
addition of MeI to the lithiated (Z)-5 has been assigned
1
by analogy to the H NMR spectra of 1-(1-methylprop-
2-enyl)-1H-1,2,3-benzotriazole17b and 3-chlorobut-1-ene.23
The methine proton in 1-(1-methylprop-2-enyl)-1H-1,2,3-
benzotriazole [CH2dCHsCH(Me)Bt] and in 3-chlorobut-
1-ene [CH2dCHsCH(Me)Cl] appears at 5.57 and 4.34
1
ppm, respectively; the H NMR spectrum of 16 showed
Starting from (EZ)-5, we have successfully carried out
two successive lithiation-electrophilic substitutions to get
(oxiranylvinyl)benzotriazoles 6a -g and 10a -d . Further-
more, hydrolysis of (oxiranylvinyl)benzotriazoles under
mild conditions provided the corresponding R,â-unsatu-
rated carbonyl derivatives. Thus, the treatment of
the signal for the allylic methine proton at 5.95 ppm.
Furthermore, no Z f E isomerization was observed.
Acid -Ca ta lyzed Hyd r olysis of (Oxir a n ylvin yl)-
ben zotr ia zoles: P r ep a r a tion of r,â-Un sa tu r a ted
Ca r bon yl Com p ou n d s. The synthetic utility of hetero-
atom-stabilized allylic systems as â-acylvinyl anion equiva-
lents is well established.3a A direct approach toward the
(24) (a) Mandai, T.; Arase, H.; Otera, J .; Kawada, M. Tetrahedron
Lett. 1985, 26, 2677. (b) Mandai, T.; Moriyama, T.; Nakayama, Y.;
Sugino, K.; Kawada, M.; Otera, J . Tetrahedron Lett. 1984, 25, 5913.
(23) Araki, S.; Ohmori, K.; Butsugan, Y. Synthesis 1984, 841.
J . Org. Chem, Vol. 69, No. 18, 2004 6021

Katritzky et al.
128.3, 127.8, 126.4, 124.5, 124.3, 122.6, 120.3, 120.2, 115.5,
109.9, 109.4, 55.8, 34.9. Anal. Calcd for C18H15ClN6: C, 61.63;
H, 4.31; N, 23.96. Found: C, 61.91; H, 4.23; N, 24.38.
6a ,b,c,e,g with p-TsOH (10 mol %) in THF at reflux for
30 min resulted in the formation of γ-hydroxy-R,â-enals
12a ,b,c,e,g in 54-86% yields (Scheme 3, Table 1). Under
identical conditions, the hydrolysis of 6d resulted in the
formation of 2-phenylfuran (14) in 61% yield. However,
the hydrolysis of 6f resulted in the formation of 12f in
low yield (ca. 10%) along with other benzotriazole-
containing byproducts as shown by the 1H NMR spectrum
of the crude material. Similarly, acidic hydrolysis of
alkylated (oxiranylvinyl)benzotriazoles 10a -d provided
γ-hydroxy-R,â-enones 13a -d in 56-82% yields (Scheme
3, Table 2). Thus, 5 functions as a synthetic equivalent
for both â-formylvinyl anion 3 and â-acylvinyl dianion
15.
1-[(E)-2-(3,3-Dip h en yloxir a n -2-yl)-1-m et h ylvin yl]-1H -
1,2,3-ben zotr ia zole (10a ). Colorless cubes (from CH2Cl2/
1
hexanes); yield, 88%; mp 102-104 °C. H NMR δ: 8.02-8.00
(m, 1H), 7.54-7.51 (m, 2H), 7.46-7.34 (m, 8H), 7.31-7.25 (m,
2H), 6.84-6.82 (m, 1H), 5.35 (dd, J ) 8.4, 1 Hz, 1H), 4.28 (d,
J ) 8.4 Hz, 1H), 2.67 (d, J ) 1 Hz, 3H). 13C NMR δ: 146.4,
139.9, 138.1, 137.1, 131.8, 128.7, 128.5, 128.3, 128.0, 127.1,
124.5, 120.3, 117.8, 111.2, 67.9, 62.5, 16.9. Crystal data:
triclinic, space group P1h, a ) 7.628(1) Å, b ) 9.693(1) Å, c )
13.398(1) Å, R ) 76.206(1)°, â ) 76.886(1)°, γ ) 72.791(1)°,
V ) 905.8(1) Å3, F(000) ) 372, Z ) 2, T ) -110 °C, µ (Mo KR)
) 0.081 mm-1, Dcalcd ) 1.296 g cm-3, crystal size 0.39 ×
0.26 × 0.18 mm3, 2θmax ) 45° (CCD area detector, Mo KR
radiation), 245 parameters, GOF ) 1.17, wR(F2) ) 0.1076 (all
2370 data), R ) 0.0485 (2145 data with I > 2σI). Anal. Calcd
for C23H19N3O: C, 78.16; H, 5.42; N, 11.89. Found: C, 78.27;
H, 5.51; N, 11.99.
Con clu sion s
In summary, we have shown that 3-chloroallylbenzo-
triazole (5), in the presence of HMPA, undergoes a
regiospecific lithiation-substitution at the CCl terminus
to give (oxiranylvinyl)benzotriazoles 6a -g. Furthermore,
lithiation-alkylation of 6a ,c takes place exclusively at the
CBt terminus to give 10a -d in good yields. Acidic
hydrolysis of 6a -g and 10a -d provided the correspond-
ing 4-hydroxyalk-2-en-1-one derivatives 12a ,b,c,e,g, and
13a -d , respectively, establishing the utility of 5 as a
â-acylvinyl anion and dianion equivalent. Furthermore,
our procedure requires only a catalytic amount of acid
for unmasking, which is milder than the oxidative
unmasking procedures used for other â-acylvinyl anion
equivalents.
2-[3-(1H -1,2,3-Ben zot r ia zol-1-yl)-5,5-d iet h yl-2,5-d ih y-
d r ofu r a n -2-yl](d ip h en yl)m eth a n ol (11). White pellets (from
CH2Cl2/hexanes); yield, 75%; mp 122-124 °C. 1H NMR δ: 8.08
(d, J ) 8.2 Hz, 1H), 7.64-7.61 (m, 2H), 7.57-7.50 (m, 4H),
7.44-7.35 (m, 5H), 7.30-7.25 (m, 2H), 5.99 (d, J ) 1.4 Hz,
1H), 5.77 (d, J ) 1.4 Hz, 1H), 3.19 (s, 1H), 2.26-2.07 (m, 2H),
2.01-1.81 (m, 2H), 1.08 (t, J ) 7.4 Hz, 3H), 0.84 (t, J ) 7.4
Hz, 3H). 13C NMR δ: 145.8, 145.5, 144.2, 139.7, 133.0, 128.7,
128.5, 128.3, 127.8, 127.5, 127.5, 126.2, 124.9, 120.5, 116.3,
111.1, 94.4, 88.5, 79.3, 31.4, 31.3, 8.8, 8.5. Crystal data:
monoclinic, space group P21/c, a ) 14.113(4) Å, b ) 9.571(3)
Å, c ) 17.403(5) Å, â ) 106.192(6)°, V ) 2257(1) Å3, F(000) )
904, Z ) 4, T ) -105 °C, µ (Mo KR) ) 0.080 mm-1, Dcalcd
)
1.252 g cm-3, crystal size 0.54 × 0.42 × 0.21 mm3, 2θmax ) 50°
(CCD area detector, Mo KR radiation), 292 parameters,
GOF ) 0.90, wR(F2) ) 0.0827 (all 3935 data), R ) 0.0366 (2459
data with I > 2σI). Anal. Calcd for C27H27N3O2: C, 76.21; H,
6.40; N, 9.87. Found: C, 75.97; H 6.44; N, 9.86.
Exp er im en ta l Section
1-[(E)-2-(3,3-Dip h en yloxir a n -2-yl)vin yl]-1H -1,2,3-b en -
zotr ia zole (6a ). White needles (from CH2Cl2/hexanes); yield,
78%; mp 122-125 °C. 1H NMR δ: 8.04 (d, J ) 8.2 Hz, 1H),
7.63 (d, J ) 14.5 Hz, 1H), 7.51 (d, J ) 7.5 Hz, 2H), 7.47-7.31
(m, 10H), 7.29-7.24 (m, 1H), 5.99 (dd, J ) 14.5, 8.0 Hz, 1H),
4.06 (d, J ) 8.0 Hz, 1H). 13C NMR δ: 146.4, 140.1, 136.5, 131.4,
128.7, 128.6, 128.4, 128.3, 127.4, 126.8, 124.9, 120.6, 116.3,
110.1, 68.3, 64.9. Anal. Calcd for C22H17N3O: C, 77.86; H, 5.05;
N, 12.38. Found: C, 77.46; H, 4.95; N, 12.49.
(2E)-4-Hyd r oxy-4,4-d ip h en ylb u t -2-en a l (12a ). Yellow
needles (from Et2O/hexanes); yield, 73%; mp 119-120 °C. H
NMR δ: 9.69 (d, J ) 7.8 Hz, 1H), 7.38-7.32 (m, 10H), 7.28 (d,
J ) 15.6 Hz, 1H), 6.51 (dd, J ) 15.6, 7.9 Hz, 1H), 2.48 (s, 1H).
13C NMR δ: 193.6, 160.3, 144.0, 130.1, 128.9, 128.4, 127.1,
79.5. Anal. Calcd for C16H14O2: C, 80.65; H, 5.92. Found: C,
80.57; H, 5.89.
1
(3E)-5-Hyd r oxy-5,5-d ip h en ylp en t-3-en -2-on e (13a ). Col-
orless needles (from CH2Cl2/hexanes); yield, 76%; mp 152-
1
(4Z)-3-(1H -1,2,3-Ben zot r ia zol-1-yl)-5-ch lor o-2-p h en yl-
p en t-4-en -2-ol (7b). White needles (from EtOAc/hexanes);
154 °C. H NMR δ: 7.35-7.25 (m, 11H), 6.48 (d, J ) 15.6 Hz,
1H), 2.52 (s, 1H), 2.29 (s, 3H). 13C NMR δ: 198.6, 150.6, 144.6,
128.7, 128.1, 127.1, 79.2, 28.4. Anal. Calcd for C17H16O2: C,
80.92; H, 6.39. Found: C, 80.50; H, 6.18.
1
yield, 30%; major diastereomer: mp 132-133 °C. H NMR δ:
7.89 (d, J ) 8.4 Hz, 1H), 7.46-7.28 (m, 5H), 7.11-7.06 (m,
2H), 7.00-6.97 (m, 1H), 6.70 (dd, J ) 9.6, 7.3 Hz, 1H), 6.47
(d, J ) 7.3 Hz, 1H), 6.15 (d, J ) 9.6 Hz, 1H), 4.81 (s, 1H), 1.73
(s, 3H). 13C NMR δ: 144.5, 144.3, 133.0, 128.2, 127.7, 127.1,
126.6, 124.1, 123.8, 119.8, 109.3, 77.4, 63.0, 27.0. Anal. Calcd
for C17H16ClN3O: C, 65.07; H, 5.14; N, 13.39. Found: C, 65.32;
H, 5.10; N, 13.32.
2-P h en ylfu r a n (14).25 Yellow oil; yield, 61%. 1H NMR δ:
7.69-7.66 (m, 2H), 7.46-7.35 (m, 3H), 7.28-7.22 (m, 1H), 6.64
(d, J ) 3.3 Hz, 1H), 6.46 (dd, J ) 3.3, 1.8 Hz, 1H). 13C NMR δ:
154.2, 142.3, 131.1, 128.9, 127.5, 124.0, 111.8, 105.1.
1-(1-Meth ylpr op-2-en yl)-1H-1,2,3-ben zotr iazole (16). Yel-
low oil; not isolated. 1H NMR δ: 8.06 (d, J ) 8.2 Hz, 1H), 7.60
(d, J ) 8.2 Hz, 1H), 7.51-7.46 (m, 1H), 7.39-7.34 (m, 1H),
6.28-6.22 (m, 2H), 5.95 (dq, J ) 6.9, 5.9 Hz, 1H), 1.92 (d, J )
6.9 Hz, 3H). 13C NMR δ: 146.2, 132.5, 130.9, 127.4, 124.1,
121.0, 120.1, 109.7, 52.1, 19.9.
1-[3-(1H-1,2,3-Ben zotr ia zol-1-yl)-1-ch lor op r op -1-en yl]-
cycloh exa n ol (8c). White needles (from EtOAc/hexanes);
1
yield, 10%; mp 113-114 °C. H NMR δ: 8.03 (d, J ) 8.2 Hz,
1H), 7.54-7.44 (m, 2H), 7.38-7.33 (m, 1H), 6.21 (t, J ) 6.5
Hz, 1H), 5.46 (d, J ) 6.5 Hz, 2H), 2.42 (s, 1H), 1.87-1.56 (m,
9H), 1.25-1.18 (m, 1H). 13C NMR δ: 146.3, 146.2, 132.9, 127.7,
124.3, 120.2, 117.8, 109.7, 74.8, 47.0, 35.6, 25.4, 21.7. Anal.
Calcd for C15H18ClN3O: C, 61.75; H, 6.22; N, 14.40. Found:
C, 62.05; H 6.27; N, 14.46.
4-(1H-1,2,3-Ben zotr iazol-1-yl)-2-ch lor o-1,1-diph en ylpen t-
2-en -1-ol (17). White needles (from Et2O/hexanes); yield, 62%;
1
mp 102-104 °C. H NMR δ: 8.05 (d, J ) 8.4 Hz, 1H), 7.54-
7.45 (m, 2H), 7.41-7.36 (m, 1H), 7.32-7.26 (m, 10H), 5.98-
5.89 (m, 2H), 3.26 (s, 1H), 1.87 (d, J ) 6.3 Hz). 13C NMR δ:
146.2, 142.5, 132.6, 129.7, 128.5, 128.4, 128.4, 127.9, 127.7,
127.4, 124.3, 120.3, 109.8, 82.9, 54.2, 20.1. Anal. Calcd for
1-[4-(1H-1,2,3-Ben zotr ia zol-1-yl)-6-ch lor o-1,5-h exa d ien -
yl]-1H-1,2,3-ben zotr ia zole (9). White needles (from EtOAc/
1
hexanes); yield, 40%; mp 156-157 °C. H NMR δ: 8.09-8.02
(m, 2H), 7.62 (d, J ) 8.2 Hz, 1H), 7.53-7.35 (m, 6H), 6.48-
6.37 (m, 3H), 6.04-5.97 (m, 1H), 3.51-3.41 (m, 1H), 3.29-
3.19 (m, 1H). 13C NMR δ: 146.1, 145.9, 132.9, 131.3, 128.9,
(25) Katritzky, A. R.; Li, J .; Gordeev, M. F. J . Org. Chem. 1993, 58,
3038.
6022 J . Org. Chem., Vol. 69, No. 18, 2004

â-Acylvinyl Anion and Dianion Equivalents
23H20ClN3O: C, 70.85; H, 5.17; N, 10.78. Found: C, 71.27;
C
13C NMR spectra for the compounds with HRMS (12e,g), and
X-ray structures for tr a n s-6b, syn -(Z)-7d , syn -(E)-7d , 8d ,
10a , and 11. This material is available free of charge via the
Internet at http://pubs.acs.org.
H, 5.24; N, 10.73.
Su p p or tin g In for m a tion Ava ila ble: General experimen-
tal methods and procedures, characterization data for com-
1
pounds 6b-g, 7c,d , 8d ,e, 10b-d , 12b,c,e,g, 13b-d , H and
J O049818J
J . Org. Chem, Vol. 69, No. 18, 2004 6023