3
Table 2: Optimization of tosylation conditions with reagent 1
through 5-exo tet cyclization involving high energetic boat
conformation 3e. The results obtained were in consistent with the
proposed mechanism. Further mechanistic investigations on ene
polyols prepared from other pentoses are in progress in our lab.
run
1
2
3
4
5
6
7
8
Tin catalysta
Bu2SnO
Bu2SnCl2
Bu2SnO
Bu2SnO
Bu2SnCl2
Bu2SnO
Bu2SnO
Bu2SnCl2
Bu2SnO
Baseb
NEt3
Solvent
DCM
DCM
THF
dioxane
THF
DCM
THF
THF
% of 4c
72
60
45
45
40
45
50
NEt3
K2CO3
K2CO3
K2CO3
DIPEA
NaHCO3
NaHCO3
K2CO3
Conclusions:
In conclusion, for the first time the reagent
[DMAPTs]+Cl-, 1 was successfully used for rapid quantitative
tosylation of aniline, phenol and 2-naphthol under essentially
neutral (base free) reaction conditions. This method would be
more useful for the tosylation of complex natural products under
neutral reaction conditions. 1 was also employed for the
unprecedented regioselective tosylation of ene polyol 3 derived
from D-ribose, involving chemoselective difunctionalization
followed by regioselective allylic tosyl hydrolysis. The main
advantages of our strategy lies in minimization of furan product 5
(which was the major product under the normal tosylation
conditions) and recovery of DMAP (80-90%) upon base work up.
Further mechanistic investigations were actively progressing in
our lab.
40
45
9
DMF
a = 5 mol% of Bu2SnO was employed
b = 1.1 eq. of base was used
c = refers to Isolated yield of primary tosyl compound 4
The hydrolysis of allylic tosyl group was also affected under
acidic conditions. We could stop the hydrolysis, at least for a
certain period of time, when we do work up with normal water to
get the ditosyl product 9. These results propelled us for further
fine tuning of reaction conditions. Having the desired product,
with moderate selectivity and yield, in our hand we further
optimized the reaction conditions (table 2) for better selectivity
and yield. we thought, based on the literature reports, that
addition of a base could enhance not only the rate of the reaction
but also the product selectivity.7
Acknowledgement:
NCK, KSR and DC thanks DST, New Delhi for funding in the
form of a project (DST-FTYS CS-148/2012), Dr C. Malla Reddy,
IISER Kolkata, IICT, Hyderabad and University of Hyderabad
for spectral data assistance. NCK also thanks Dr M. Sridhar
Reddy, CDRI Luknow for useful discussions.
In this direction the reagent 1 was treated with various tin
catalysts with different bases in a range of solvents and the best
results were obtained when ene polyol 3 was treated with 2.1 eq.
0
of 1 and 1.1 eq. of NEt3 in DCM at 10 C for 30 min to furnish
the product 4, after brine work up, in 72% yield (entry 1 in table
2) along with the minor furan derivative 5 (9%) in 8:1 ratio. This
clearly demonstrates the utility of NEt3 in maximum product
turnover with minimal formation of furan product (Scheme 5).
All other reaction conditions employing different tin catalysts
and bases in various solvents produced lesser yields of the
desired product 4. we propose a tentative mechanism as depicted
in figure 2 (though the exact mechanism, at this juncture, is not
known for which further studies with other ene polyols are
progress in our lab) in which treatment of ene polyol 3 with
Bu2SnO in DCM would selectively produce dibutyl stannylene
acetal 3a of terminal diol of 2-ene 4,5,6,7-polyol which
underwent regioselective tosylation at primary hydroxyl to
produce primary tosyl derivative 3b still as a tin complex. This
tin complex 3b would be transformed into stannylene derivative
3c through intramolecular 6-exo tet cyclization at the tin. There
are two competing pathways for complex 3c for further reaction.
In a major pathway 3c undergo regioselective allylic hydroxyl
tosylation to furnish ditosyl derivative 9. In a minor pathway 3c
undergo intramolecular SN2 displacement of primary tosyl group
References and notes
1.
Wilkinson, S. G. In Comprehensive Organic Chemistry; Stoddart,
J. F., Ed; Pergamon Press: Oxford, 1979; Vol. 1, Chapter 4.1, pp
579-706.
2.
3.
4.
5.
Greene, T. W.; Wuts, P. G. M. Protective Groups In Organic
Synthesis, second ed.; John Wiley & Sons: New York, 1991
Orita, A.; Mitsutome, A.; Otera, J. J. Org. Chem. 1998, 63, 2420–
2421.
Tanino, K.; Shimuzu, T.; Kuwahara, M.; Kuwajima, I. J. Org.
Chem. 1998, 63, 2422–2423.
Kolb, H. C.; Van Nieuwenhze, M. S.; Sharpless, K. B. Chem. Rev.
1994, 94, 2483.
6.
7.
O, Donnell, C. J.; Burke, S. D. J. Org. Chem. 1998, 63, 8614.
Martinelli, M. J.; Nayyar, N. K.; Moher, E. D.; Dhokte, U. P.;
Pawlak, J. M.; Vaidyanathan, R. Org. Lett. 1999, 1, 447-450
Shanzer, A. Tetrahedron Lett. 1980, 21, 221.
8.
9.
David, S.; Hanessian, S. Tetrahedron 1985, 41, 643
10. Simas, A. B. C.; Da Silva A. A. T.; Filho, T. D. S.; Barroso, P. T.
W. Tetrahedron Lett. 2009, 50, 2744-2746.
11. Al- Mugahad, H.; Grindley, T. B. Carbohydr. Res. 2004, 339,
2607.
12. Nagashima, N.; Ohno, M. Chem. Pharm. Bull. 1991, 39, 1972.
13. Gamedge, M. P.; Maseko, R. B.; Chigondo, F.; Nkamble, C. M.
Tetrahedron Lett. 2012, 53, 5929-5932.
14. Dolhem, F.; Smiljanic, N.; Livre, C.; Demailly, G. Tetrahedron
2006, 62, 7756-7761.
15. Jampel, E. G.; Wakselman, M. J. C. S. Chem. Cumm. 1980, 994.
16. Inkster, A. H. J.; Liu, K.; Ait-Mohand, S.; Schaffer, P.; Guerin, B.;
Ruth, T. J.; Star, T. Chem. Eur. J. 2012, 18, 11079-87.
17. Yashuhara, A.; Kameda, M.; Sakamoto. Chem. Pharm. Bull. 1999,
47, 809.
18. Kamal, J. A.; Reddy, E. S.; Bharathi, D. V. Tetrahedron Lett.
2008, 49, 348.
19. Meshram, G. A.; Patil, V. D. Tetrahedron Lett. 2009, 50, 1117.
20. Singh, R. P.; Kamble, R. M.; Chandra, K. L.; Saravanane, P.;
Singh, V. K. Tetrahedron 2001, 57, 241.
OH
O
OH
O
Bu2SnO
DCM
OEt
TsO
OEt
3
O
Sn
O
OH
O
Sn
OH
Bu
3a
3b
Bu
Bu
Bu
Cl
Bu
Sn
HO
OH
Minor
TsO
OH
O
HO
O
Bu
5 exo tet
OEt
OEt
O
O
O
O
O
OEt
Sn
5
TsO
Bu
Bu
O
3c
allylic
Major
tosylation
OH O
Preferential
Hydrolysis
OH
O
TsO
OEt
TsO
OEt
brine
OH OH
OH OTs
4
9
Figure 2: Rationale for the tosylation of 3 with the reagent 1.