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Stereochemistry of the vinylogous sN2′ reaction
Tetrahedron Letters Vol. 22, pp 585 - 586 QPerganon Press Ltd. 1981. Printed in Great Britain
STRRROCRRMISTRYOF THE VINYLCCCUS SN2' REACTION William S. Murphy* and Brendan O'Mahony Chemistry Department University College Cork, Ireland
Theoretical treatment indicates that the stereochemistryof both the vinylogous SN2' and 1,6conjugate elimination reaction will be opposite to that of the SN2' and 1,4-conjugate elimination reaction.
Interest in the SN2' reaction continues unabated.' Attention has centred not alone on the mechanism' but also on synthetic' and biosynthetic' applications. In addition, interest in the related 1,4-conjugateelimination reaction is growing."'
Most theoretical analyses6 of the SN2' reaction have indicated a preference for SW attack by the nucleophile. However, the possibility of anti stereochemistryhas been allowed for in some instances.6cse In practice although SW stereochemistryhas been most sb,s have diverged from this. generally observed2C'7 recent results
We have now extended orbital symmetry methods6c to the vinylogous SN2' reaction (1).
The LIJMOof the pentadienyl cation is $3. mediate between sp3 and p.
In the transition state C-l and C-5 will be inter-
Mixing the 2s and 2p AO's of C-l and C-5 results in the structure
(II) for the LUMO of the pentadienyl cation in the transition state. It is immediately apparent that (II) is symmetric relative to a mirror plane through its mid-point. The corresponding ally1 transition state, structure (III), is antisymmetric relative to the same symmetry element.
It follows6c that when C-l bond formation is synchronous with C-5 bond cleavage, the
attacking nucleophile must enter sun to the leaving group. Where C-l bond formation is concerted but not synchronous with C-5 bond cleavage, the nucleophile must enter anti to the
585
586
leaving group. Hence all things being equal, the conditions which favour sun-SN2' reactions of ally1 systems should result in an anti
S,2' reaction in pentadienyl systems and
vice versa.
Extension of this methodology6C to 1,6-conjugateelimination by either a concerted or Elcb mechanism shows that an anti process is favoured.
The stereochemistryof the vinylogous SN2' acetolysis of 6@-bromoandrost-4-ene-3,17dione,.a longstanding problem,' has now been shown" to be at least predominantly syn. 1,6-Conjugate elimination is known" but is of unknown stereochemistry.
References
1.
R.M. Magid, Tetrahedron,
2. (a)
F.G. Bordwell, P.F. Wiley and T.G. Mecca, J.
(b)
36,
1901, and references therein.
T. Oritani and K.H. Overton, J.C.S. O.S. Fruchey, J.
3.
1980,
Amer.
Chem.
N. Ikota and B. Ganem, J.
Conrn.,
Chem.
1978, 454;
Chem.
Sot.,
1978,
5.
K.H. Overton, Chem.
Sot.
Chem.
1978, 467.
Corn...
1979, 8, 447 and references therein.
Rev.,
R.K. Hill and M.G. Bock, J.
(c) R.M. Magid and
100, 351; P.C. Cherry, G.I.
Gregory, C.E. Newall, P. Ward and N.S. Watson, J.C.S. 4.
1975, 97, 132;
Sot.,
1979, 101, 2107.
Sot.,
Amer.
Chem.
Amer.
Amer.
Chem.
Sot,,
1978,
100, 637 and references therein;
A. Eschenmoser, paper presented at the RSC International Symposium, St. Andrews, Scotland, 21-25 July 1980. 6.(a) K. Fukui and H. Fujimoto, BulZ. Reel.
1089;
Trav.
Chim.
1975, 523;
9.
G. Stork and A.F. Kreft, J.
C.
1973, 807;
Chem.
(b) W. Dreuth,
Chem.
Comm.,
1968,
(e) R.L. Yates, N.D. Epiotis
(f) C.L. Liotta, Tetrahedron
1978, 34,
1665.
Amer.
Chem.
Sot.,
1956, 78, 4609.
Amer.
Chem.
Sot.,
1977, 99, 3850; A.A. Dobbie and
Comm.,
1977, 722.
Djerassi, G. Rosenkranz, J. Romo, S. Kaufmann and J. Pataki, J.
1950, 72, 10.
(c) N.T. Ahn, J.C.S.
E. Toromanoff, Tetrahedron,
G. Stork and W.N. White, J.
K.H. Overton, J.C.S.
Fr.,
1967, 40, 2018;
Chem. Sot., 1975, 97, 6615;
Amer. (g)
Japan,
1967, 86, 318;
Pays-Bas,
and F. Bernardi, J.
8.
Sot.
(d) J. Mathieu, &rll. Sot. Chim.
Letters,
7.
Chem.
4534.
R.D. Burnett and D.N. Kirk, J.C.S.
(Received in UK 17 November 1980)
Perkin
1,
1973, 1830.
Amer.
Chem.
SOC.,
STRRROCRRMISTRYOF THE VINYLCCCUS SN2' REACTION William S. Murphy* and Brendan O'Mahony Chemistry Department University College Cork, Ireland
Theoretical treatment indicates that the stereochemistryof both the vinylogous SN2' and 1,6conjugate elimination reaction will be opposite to that of the SN2' and 1,4-conjugate elimination reaction.
Interest in the SN2' reaction continues unabated.' Attention has centred not alone on the mechanism' but also on synthetic' and biosynthetic' applications. In addition, interest in the related 1,4-conjugateelimination reaction is growing."'
Most theoretical analyses6 of the SN2' reaction have indicated a preference for SW attack by the nucleophile. However, the possibility of anti stereochemistryhas been allowed for in some instances.6cse In practice although SW stereochemistryhas been most sb,s have diverged from this. generally observed2C'7 recent results
We have now extended orbital symmetry methods6c to the vinylogous SN2' reaction (1).
The LIJMOof the pentadienyl cation is $3. mediate between sp3 and p.
In the transition state C-l and C-5 will be inter-
Mixing the 2s and 2p AO's of C-l and C-5 results in the structure
(II) for the LUMO of the pentadienyl cation in the transition state. It is immediately apparent that (II) is symmetric relative to a mirror plane through its mid-point. The corresponding ally1 transition state, structure (III), is antisymmetric relative to the same symmetry element.
It follows6c that when C-l bond formation is synchronous with C-5 bond cleavage, the
attacking nucleophile must enter sun to the leaving group. Where C-l bond formation is concerted but not synchronous with C-5 bond cleavage, the nucleophile must enter anti to the
585
586
leaving group. Hence all things being equal, the conditions which favour sun-SN2' reactions of ally1 systems should result in an anti
S,2' reaction in pentadienyl systems and
vice versa.
Extension of this methodology6C to 1,6-conjugateelimination by either a concerted or Elcb mechanism shows that an anti process is favoured.
The stereochemistryof the vinylogous SN2' acetolysis of 6@-bromoandrost-4-ene-3,17dione,.a longstanding problem,' has now been shown" to be at least predominantly syn. 1,6-Conjugate elimination is known" but is of unknown stereochemistry.
References
1.
R.M. Magid, Tetrahedron,
2. (a)
F.G. Bordwell, P.F. Wiley and T.G. Mecca, J.
(b)
36,
1901, and references therein.
T. Oritani and K.H. Overton, J.C.S. O.S. Fruchey, J.
3.
1980,
Amer.
Chem.
N. Ikota and B. Ganem, J.
Conrn.,
Chem.
1978, 454;
Chem.
Sot.,
1978,
5.
K.H. Overton, Chem.
Sot.
Chem.
1978, 467.
Corn...
1979, 8, 447 and references therein.
Rev.,
R.K. Hill and M.G. Bock, J.
(c) R.M. Magid and
100, 351; P.C. Cherry, G.I.
Gregory, C.E. Newall, P. Ward and N.S. Watson, J.C.S. 4.
1975, 97, 132;
Sot.,
1979, 101, 2107.
Sot.,
Amer.
Chem.
Amer.
Amer.
Chem.
Sot,,
1978,
100, 637 and references therein;
A. Eschenmoser, paper presented at the RSC International Symposium, St. Andrews, Scotland, 21-25 July 1980. 6.(a) K. Fukui and H. Fujimoto, BulZ. Reel.
1089;
Trav.
Chim.
1975, 523;
9.
G. Stork and A.F. Kreft, J.
C.
1973, 807;
Chem.
(b) W. Dreuth,
Chem.
Comm.,
1968,
(e) R.L. Yates, N.D. Epiotis
(f) C.L. Liotta, Tetrahedron
1978, 34,
1665.
Amer.
Chem.
Sot.,
1956, 78, 4609.
Amer.
Chem.
Sot.,
1977, 99, 3850; A.A. Dobbie and
Comm.,
1977, 722.
Djerassi, G. Rosenkranz, J. Romo, S. Kaufmann and J. Pataki, J.
1950, 72, 10.
(c) N.T. Ahn, J.C.S.
E. Toromanoff, Tetrahedron,
G. Stork and W.N. White, J.
K.H. Overton, J.C.S.
Fr.,
1967, 40, 2018;
Chem. Sot., 1975, 97, 6615;
Amer. (g)
Japan,
1967, 86, 318;
Pays-Bas,
and F. Bernardi, J.
8.
Sot.
(d) J. Mathieu, &rll. Sot. Chim.
Letters,
7.
Chem.
4534.
R.D. Burnett and D.N. Kirk, J.C.S.
(Received in UK 17 November 1980)
Perkin
1,
1973, 1830.
Amer.
Chem.
SOC.,