Transcript Baldwin`s Rules

Baldwin’s Rules
Nadia Fleary-Roberts
02/05/12
Baldwin’s rules for ring closure
•Proposed in 1976 by Sir Jack Baldwin
•Guidelines for ring closing reactions of 3- to 7-membered rings-
•empirical rules derived from experimental observations
J. Chem. Soc. Chem. Commum., 1976, 734-736
Advanced organic chemistry, March p 212
Clayden 1st Edn p 1140 2nd Edn p 810
Dr. F. Pradaux, Sheffield University
Nomenclature
1. Ring size
3, 4,......7
Number Indicates the size of
the ring being formed
Nomenclature
2. Bond
The bond broken as the
ring is formed is
outside the new ring
The bond broken as the
ring is formed is inside
the ring
exo
X-
X
Y-
Y
endo
X-
Y
X
Y-
Nomenclature
3. Geometry
geometry of the carbon undergoing the ring closing can be describes as:
sp3
tetrahedral carbon
tet
sp2
trigonal carbon
trig
sp
digonal carbon
dig
For example.....
Reactions can be favoured or disfavoured
•kinetic favourability of a reaction
• A disfavoured reaction does not mean that the reaction will
not occur -just that it is more difficult
•Disfavoured cases require severe distortion of bond angles
and distances
Ideal bond angles
•Favoured cyclisations enable terminal atoms to achieve proper geometries
Trigonal carbons
(Bürgi-Dunitz)
Tetrahedral carbons
(Walden inversion)
Digonal carbons
Tetrahedral systems
all exo-tet cyclisations are favoured
Trigonal systems
All exo-trig cyclisatons are favourable
5-endo trig are disfavoured!
Favoured exo-tet and exo-trig
Exo-tet
Exo-trig
Disfavoured 5-Endo-trig
Disfavoured 5-Endo-trig...iodocyclisation
•Iodocyclisation forms the disfavoured “anti-Baldwin” endo-trig product
•WHY?
1)Overwhelming attraction between nucleophile and electrophile
2)No kinetically favoured alternative pathways- 4-exo-tet would be too strained
Knight et.al. Tetrahedron Lett. 1998, 39, 8909
however
•5-exo-trig strongly favoured over the 5-endo-trig
Digonal systems
All endo-dig are favoured
Endo-dig rationale
•Alkyne has two π* orbitals-one in the plane of the ring
Disfavoured 3- and 4-exo-dig
•Nucleophile cannot attack at the required 120° angle
Exceptions to the Baldwin’s rules
•second row elements
Why?
•Long C-S bond
•Sulfur has empty 3d orbitals
•cations
Summary
Size
Exo
Endo
Tet
Trig
Dig
3


4

5
Tet
Trig
Dig
X
X


X
X




X
X

6



X


7





Intramolecular endocyclic alkylation of ketone
enolates
Nomenclature
enolexo or enolendo orientation of the enolate C-C bond
exo-tet or exo-trig with respect to the C-Y terminus
6 to 7 Favoured
3 to 5 Disfavoured
3 to 7 Favoured
Baldwin, Kruse, JACS Chem Commun. 1977, 233
Oxygen alkylation vs. Carbon alkylation
(Compare with disfavoured 5-endo trig)
(Compare with favoured 6-endo-trig)
Oxygen alkylation vs. Carbon alkylation
X
M
O
X
O
M
O
•Oxygen alkylation -electrophile approaches in plane of the enolate
Carbon alkylation in 6-enolendo possible
•Perpendicular approach to the enolate
Intramolecular aldol condensations
Favoured 3 to 7
disfavoured 3 to 5
favoured 6 to 7
Baldwin, Tetrahedron, 1982, 38, 2939
5-enolendo-exo-trig vs. 6-enolendo exo-trig
•6-enolendo-exo-trig exclusively formed.
Summary
Exo-Tet
Exo-Trig
Size
enolendo
enolexo
enolendo
enolexo
3
X

X

4
X

X

5
X

X

6




7




Just remember.....
1. Exo-tet and endo-trig favoured
2. 5-endo trig disfavoured*
3. Endo-dig favoured
Endocyclic reactions
1. Enolexo endo-tet and trig are favoured
Other Than Nucleophilic Cases
• Radical Processes
(homolitic):
3-exo-Trig
4-endo-Trig
• Cationic Processes:
6-endo-Trig
5-endo-Trig