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Baldwins Rules
Qualitative set of generalization on the probability of a ring closure (RC) Empirical rules formulated from observations and stereoelectronic reasoning Describe kinetic feasibility of ring closure Physical basis lie in stereochemical The rules do not apply to second row elements and to pericyclic reactions
Terminology/Classification (1)
Prefix exo when the breaking bond is exocyclic to the smallest ring formed.
exo XY X Y-
Prefix endo when the breaking bond is endocyclic to the smallest ring formed.
endo
Y-
Terminology/Classification (2)
Numerical prefix describe the size of formed ring. Sufixes Tet, Trig and Dig indicate the geometry of the carbon undergoing the RC. Tetrahedral for sp3 carbon Trigonal for sp2 carbon Digonal for sp carbon
3 2 1 4 3
5-exo-Tet
2 1
X-
Y-
X-
X-
3-exo-Tet
4 3 2 1 5 6
4-exo-Tet
4 3
Y 5-exo-Tet
4 3 2 5
X-
6-exo-Tet Y
Y X1
Y 7-exo-Tet
-7
5-endo-Tet
X 6-endo-Tet
1
Y
3
X-
X-
3-exo-Trig
2
4-exo-Trig
2
5-exo-Trig
4 3
6-exo-Trig
4 3 5
Y 7-exo-Trig
4 5 3
1X 7
X1
Y
3
Y
4
Y
5 1
Y
1
Y
2 1
X-
3-endo-Trig
4-endo-Trig
5-endo-Trig
6-endo-Trig
7-endo-Trig
Y
5-Di
-Di
-Di
Y -Di
-Di
-Di
-Di
5-
-Di
-Di
-Di
Y
-
- ri
Cationic Processes:
- ri
5-
- ri
Attack Trajectories
Favoured paths to transition states are:
Wald n inv rsi n Y
XE
E = 80
Y-
Tetrahedral Systems
Brgi-Dunitz Y
X
E
Trigonal Systems
E = 09
XE
X C C
E
E
E = 20
C C Y
igonal Systems
n
1
H2N
Br
3-exo-Tet
ccur
O O S O 6t? S O O
6-
t Di fav ur
: R acti
clu iv l i t r
l cular
n
2
4 5
OH
O H
ibl
5-exo-Trig
O O
H H O OH
HO O
OH
5-e o-Trig
OMe
O
3 2 1 4
O OMe OH Base
1 3 2 4
O
5
OMe
3
5
2 5 1
R O R
(CH2OH)2
OH R HO H OH R H2 O R O R O
H - H2 O
OH R O R
R O
5-exo-Trig Fa o red
R O
CO2Me
5
MeO2C
CO2Me
5-endo-Trig %
NH2
HN
1
MeO2C
4 5
HN 1
ontrol ex eriment PhCH2NH2 CO2Me
5-exo-Trig %
O
H N CO2Me % O %
Ph
H N 1
Ph
O H N H OMe
H N O OMe
N lone air an not rea h T* or ital of Mi hael a e tor nitz angle atta not ossi le
Digonal carbon
All endo-Dig cyclizations are favoured
T* ina O O Ar
1 2
essi le
O
3 4 5
Ar
5-endo- ig
X x
Xx
+ O
Exoclyclic alkylations
(Enolexo)-Exo- et +
-
3- to 7- membere RC Favoured
Y-
Exoclyclic reactions
(Enolexo)-Exo- rig
-
Y-
3- to 7- membered RC Favoured
RESTRICCIONES ESTEREOELECTRONICAS.
Intramolecular alkylations of ketone enolates Intramolecular aldol condensations
180 atta
C alkylatio s O
O alkylatio s
O alkylatio s
0% 5-(enolendo) -exo-tet
X M O O M
X O
0% 6-exo-Tet
Statistics : 4 possibilities to form a 5 membered ring 2 possibilities to form a 6 membered ring Previsions : 6 membered ring would be predominant or exclusive
-1
Formation of cyclohexanone totally dominates over even statistically preferred cyclopentanones production.
O R Co2(CO)6
LA
H RZ RE
Co2(CO)6 R
LA
H RZ RE
Co(CO)3 Co(CO)3 R
6-(enolendo)-exo-trig
of cyclobutane ketones :
Co2(CO)6 R1 O
O R1 Co2(CO)6
R2
Le is
id
R2
6-exo- rig
LA
H O R2
Co2(CO)6 R1
LA
H O
Co(CO)3 Co(CO)3 R1
R2
4-(enolexo)-exo-trig
Conclusion
Only give information about whether processes are favoured or disfavoured and not allowed and forbidden. Nucleophilic RC feasibility strongly depends on ring size, geometry of reacting atom and exo or endo nature of reaction. Structural modification can dramatically affect the cyclization mode. If favoured trajectory of attack valid, then reaction will follow the Baldwins rules.
Summary (1)
Size Tet 3 4 5 6 7 Exo Trig Dig X X X X Tet Endo Trig X X X Dig
Summary (2)
Exo-Tet Size 3 4 5 6 7 Exo-Trig enolendo enolexo enolendo enolexo X X X X X X
References
J. E. Baldwin, J. Chem. Soc., Chem. Commun. 1976, 734. J. E. Baldwin, J. Cutting, W. Dupont, L. Kruse, L. Silberman, R. C. Thomas, J. Chem. Soc., Chem. Commun. 1976, 736. J. E. Baldwin, R. C. Thomas, L. Kruse, L. Silberman, J. Org. Chem, 1977, 42, 3846. J. E. Baldwin, L. Kruse, J. Chem. Soc., Chem. Commun. 1977, 233. J. E. Baldwin, M. J. Lusch, Tetrahedron, 1982, 38, 2939. C. D. Johnson, Acc. Chem. Res. 1993, 26, 476. J. Clayden, N. Greeves, S. Warren, P. Wothers, Oxford, chapter 42, p 1140. D. A. Evans, internet course.