Stereoselective Olefination of Carbonyl Compounds with N-Benzyl- and N-Allylbenzotriazoles by Low-Valent Titanium-Promoted Dehydroxybenzotriazolylation

Full text of DOI:10.1021/jo962035g

2
38
J . Org. Chem. 1997, 62, 238-239
Ster eoselective Olefin a tion of Ca r bon yl
Com p ou n d s w ith N-Ben zyl- a n d
N-Allylben zotr ia zoles by Low -Va len t
Tita n iu m -P r om oted
Sch em e 1
Deh yd r oxyben zotr ia zolyla tion
Alan R. Katritzky* and J ianqing Li
Center for Heterocyclic Compounds, Department of
Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Received October 31, 1996
Olefination of aldehydes and ketones is very important
in organic synthesis. Wittig reactions represent a highly
effective and general method of alkene formation from
We now show that lithiation of N-allyl- or N-benzyl-
benzotriazoles 1 followed by reaction with aldehydes or
ketones to give N-(R-hydroxyallyl)- or N-(R-hydroxy-
benzyl)benzotriazole derivatives 3, and subsequent treat-
ment in situ with low-valent titanium generated from
lithium and titanium(III) chloride in THF or DME,
affords the corresponding alkenes 4 in good yields with
the trans-isomers predominant (Scheme 1 and Table 1).
1
,2
carbonyl derivatives, but their low stereoselectivity for
allylic and benzylic ylides, the difficult removal of byprod-
uct phosphine oxide, and poor reactivity with hindered
ketones have all encouraged the development of alterna-
tive protocols. Among such complementary methods
previously developed, the Peterson and J ulia reactions
have shown significant advantages and are the most
N-Allyl- and N-benzylbenzotriazoles 1 are easily pre-
13a-c
pared from allyl or benzyl halides or alcohols.
In the
1
-3
frequently used.
However, they are not without
present work, compounds 1a , 1b, and 1d 16 were
14
15
drawbacks. Peterson reactions require the separation of
diastereomeric intermediates in order to control the
stereoselectivity of the alkenes produced. Disadvantages
of the original J ulia protocol reaction are a rather lengthy
procedure and difficulties in the preparation of trisub-
stituted alkenes. More recently, an improved J ulia
coupling reaction has employed benzothiazolyl sulfones;4
this gives excellent stereoselectivity for aliphatic sulfones,
but in the cases of allylic and benzylic benzothiazolyl
prepared by literature methods. Compound 1c was
obtained from the reaction of benzotriazole and the
corresponding allyl halide in the presence of sodium
13a
hydroxide in ethanol according to a literature analogy.
In order to avoid complications in the monitoring of the
intermediates 3 (TLC and 1H NMR), benzotriazol-1-yl
-6
isomers 1 were used in the present study. However, a
mixture of benzotriazol-1-yl and benzotriazol-2-yl deriva-
tive 1c was also tested for the transformation (Scheme
6
,7
sulfones, the trans:cis outcome is less predictable.
1
), and the result showed no difference from the use solely
During the last two decades, low-valent titanium has
been found to be a useful reagent for the preparation of
alkenes from aldehydes and ketones by reductive deoxy-
genation.8 Very recently, such McMurry reaction ana-
logs have been extended to the intramolecular coupling
of ketones with amides.10 Low-valent titanium can also
of the benzotriazol-1-yl derivative 1c.
Compound 1 was reacted with 1 equiv of n-butyl-
lithium in THF at -78 °C for 1 h to generate a dark blue
solution that was treated with a solution of an aldehyde
or a ketone 2 (1 equiv) in THF for 2 h to give a
,9
1
distereomeric mixture 3 in high yield based on H NMR
be used in the deprotection of allyl and benzyl derivatives
data with a nearly 1:1 ratio. The alkylation occurred
regioselectively at the carbon attached to the benzotria-
zolyl group; no γ-alkylated products were found in the
of alcohols and amines.1
1,12
However, olefin formation
via the reductive elimination of two different hetero
atoms R to each other using low-valent titanium has not
previously been reported.
1
cases of 1c-d by H NMR. After aqueous workup, the
intermediate 3 was treated with low-valent titanium in
THF or DME to give the alkene 4. When THF was used
in the case of allylbenzotriazoles 1c,d , small amounts of
(1) Gosney, I.; Lloyd, D. In Comprehensive Organic Functional
Group Transformations; Katritzky, A. R., Meth-Cohn, O., Rees, C. W.,
Eds.; Pergamon Press: New York, 1995; Vol. I, 719.
reduced byproduct alkanes were detected by GCMS,
17
which indicated that THF acted as a proton source. The
use of DME instead of THF suppressed the formation of
byproduct alkanes, with the ratio of E:Z alkenes unaf-
fected. Since the low-valent titanium-promoted dehy-
droxybenzotriazolylation gives a high proportion of E-
alkenes and the reaction in THF gives reduced products
as alkanes, the reaction pathway probably involves free-
(
2) Kelly, S. E. In Comprehensive Organic Synthesis; Trost, B. M.,
Ed.; Pergamon Press: New York, 1991; Vol. I, Part I, p 729.
3) Ager, D. J .; East, M. B. Asymmetric Synthetic Methodology; CRC
Press: New York, 1995; p 187.
4) Baudin, J . B.; Hareau, G.; J ulia, S. A.; Ruel, O. Tetrahedron Lett.
991, 32, 1175.
5) Baudin, J . B.; Hareau, G.; J ulia, S. A.; Ruel, O. Bull. Soc. Chim.
Fr. 1993, 130, 336.
6) Baudin, J . B.; Hareau, G.; J ulia, S. A.; Lorne, R.; Ruel, O. Bull.
Soc. Chim. Fr. 1993, 130, 856.
7) Bellingham, R.; J arowicki, K.; Kocienski, P.; Martin, V. Synthesis
996, 285.
(
(
1
(
(
1
8
radical intermediates as proposed by McMurry.
The low-valent titanium was prepared on the basis of
(
1
12,18
literature procedure.
To optimize the reaction yields,
(
(
(
8) Pons, J .-M.; Santelli, M. Tetrahedron 1988, 44, 4295.
9) McMurry, J . E. Chem. Rev. 1989, 89, 1513.
10) FÅrstner, A.; Ernst, A.; Krause, H.; Ptock, A. Tetrahedron 1996,
(14) Gibson, M. S. J . Chem. Soc. 1956, 1076.
(15) Katritzky, A. R.; Gordeev, M. F.; Greenhill, J . V.; Steel, P. J . J .
Chem. Soc., Perkin Trans. 1 1992, 1111.
5
2, 7329.
(11) Kadam, S. M.; Nayak, S. K.; Banerji, A. Tetrahedron 1992, 33,
5
129.
(16) Katritzky, A. R.; Xie, L.; Toader, D.; Serdyuk, L. J . Am. Chem.
Soc. 1995, 117, 12015.
(17) Reetz, M. T.; Quaiser, S. A.; Merk, C. Chem. Ber. 1996, 129,
741.
(
(
12) Talukdar, S.; Banerji, A. Synth. Commum. 1995, 25, 813.
13) (a) Katritzky, A. R.; Li, J .; Malhotra, N. Liebigs Ann. Chem.
1
992, 843. (b) Hopff, H.; L u¨ ssi, H. Helv. Chim. Acta 1963, 46, 1052.
(
c) Katritzky, A. R.; Perumal, S.; Fan, W.-Q. J . Chem. Soc., Perkin
(18) McMurry, J . E.; Fleming, M. P.; Kees, K. L.; Krepski, L. R. J .
Org. Chem. 1978, 43, 3255.
Trans. 2 1990, 2059.
S0022-3263(96)02035-X CCC: $14.00 © 1997 American Chemical Society

Communications
J . Org. Chem., Vol. 62, No. 2, 1997 239
Ta ble 1. P r ep a r a tion of Olefin s 4a -h fr om Ben zyl- a n d Allylben zotr ia zoles 1 a n d Ca r bon yl Com p ou n d s 2
a 10:1 ratio (by equivalent) of low-valent titanium vs
substrates 3 was employed. However, the ratio of 5:1
worked equally well in several reactions.
proton coupling constants, and NOE spectra and the
Z-isomers were detected by H NMR and GCMS. The
E:Z ratios were determined from the GCMS of the crude
products.
1
As shown in Table 1, the reaction can be applied to
aromatic and aliphatic aldehydes and ketones as well as
In summary, a convenient and stereocontrolled olefi-
nation of aldehydes and ketones with N-allyl- and N-
benzylbenzotriazoles is described. In terms of high
stereoselectivity, easy separation, unneccesary isolation
of diastereoisomers, and simple procedure for both di- and
trisubstituted alkenes, this method complements the
three most frequently used protocols for alkene formation
from carbonyl compounds: the Wittig, Peterson, and
J ulia reactions. Further investigations of the scope and
limitations of this dehydroxybenzotriazolylation pro-
moted by low-valent titanium are underway.
1
cyclic ketones. However, when the adduct 3 (R
)
2
3
p-MeC
6 4
H ; R ) R ) Ph; derived from benzophenone and
1
a ) was treated with low-valent titanium in THF, the
expected product 4 was detected by GCMS in relatively
low yield and GCMS of the reaction mixture indicated
the occurrence of retroreaction under these conditions.
1
Fortunately, the treatment of 3 (R ) 3,3-dimethylallyl;
2
3
R ) R ) Ph; derived from benzophenone and 1c) with
low-valent titanium in DME afforded the alkene 4e in
7
5% yield. Presumably, the solvent THF led to the
retroreaction of 3 in the above case. The stereoselectivity
depended on the substituents as illustrated by the E:Z
ratios of products 4c and 4d as well as 4g and 4h .
Obviously, N-benzylbenzotriazole gave better stereo-
selectivity than N-allylbenzotriazole as shown by the E:Z
ratios of alkenes 4a and 4f. All products were character-
Ack n ow led gm en t. We thank Professor J ames W.
Leahy (UC, Berkeley) for helpful discussion.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedure for the preparation of trans-1-(N-benzotriazolyl)-4-
methyl-2-butene (1c) and alkenes 4a -h and the character-
ization data of the compounds described above (4 pages).
1
13
ized by H and C NMR and microanalysis. The struc-
tures of the E-alkenes were confirmed by large trans-
J O962035G