Bald Wins Rules

8/6/2019 Bald Wins Rules

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Baldwins Rulesfor

Ring Closure

Dr Fabienne PradauxWednesday 2nd February 2005


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Baldwins Rules

Qualitative set of generalization on the probability ofa ring closure (RC)

Empirical rules formulated from observations andstereoelectronic reasoning

Describe kinetic feasibility of ring closure

Physical basis lie in stereochemical

The rules do not apply to second row elements and topericyclic reactions


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Terminology/Classification (1)

Prefix exo when thebreaking bond isexocyclic to the

smallest ring formed.

Prefix endo when thebreaking bond isendocyclic to thesmallest ring formed.

X-

exo

X

Y Y-

X- Y XY-

endo


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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

X-X

Y Y-

5-exo-Tet51

2

3

4

51

2

3

4


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Rules for Ring Closure (1)

Tetrahedral Systems 3 to 7-exo-Tet are all favoured processes 5 to 6-endo-Tet are disfavoured

-XY

X-Y

X-

Y X- Y

X-

YX-

Y

X-

Y

5-exo-Tet3-exo-Tet 4-exo-Tet 6-exo-Tet

7-exo-Tet 5-endo-Tet 6-endo-Tet

12

35

1

2

3

5

6

7

1

2

3

1

2

3

1

2 3

4

4

4

5

6

4

1

2

3

45

6

1

2

3

4


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Trigonal systems 3 to 7-exo-Trig are all favoured processes 3 to 5-endo-Trig are disfavoured; 6 to 7-endo-Trig are

favoured

-XY

X-Y

X-

Y X- Y X-

Y

X-

Y

X-

Y

5-exo-Trig3-exo-Trig 4-exo-Trig 6-exo-Trig 7-exo-Trig

5-endo-Trig 6-endo-Trig

-XY

-X Y

X-

Y

3-endo-Trig 4-endo-Trig 7-endo-Trig

12

3

51

23

5

6

71

2

3

1

2

3

1

2 3

4

44

5

6

4

1

2

3

4

5

6

1

2

3

4

1

2

3

1

2

3

4

5

71

2

3

45

6


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Digonal Systems 3 to 4-exo-Dig are disfavoured processes; 5 to 7-exo-

Dig are favoured

3 to 7-endo-Dig are favoured

- -

Y-

Y-

-

-

Y

-

Y

5- -Di- -Di - -Di - -Di - -Di

5- -Di - -Di

- Y-

Y

-

Y

- -Di - -Di - -Di

YY

Y


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Other Than Nucleophilic Cases

Radical Processes(homolitic):

Cationic Processes:

3- - ri

- - ri

- - ri

5- - ri


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Attack Trajectories Favoured paths to transition states are:

Y-E

X Y-E

E = 80

Wald ninv rsi n

Y

X-

E

E = 09

Brgi-Dunitz X

Y

E

C C

E

E

X-

E = 20C C

Y

XE E

Y

Tetrahedral Systems

Trigonal Systems

igonal Systems


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Favoured and Disfavoured

Favoured RC will be those in which length andnature of linking chain enables terminal atoms to

achieve required trajectory to form final ring bond

Disfavoured RC would require severe bond angle

and distances distortion, so the desired RC will bedifficult (if available, alternative pathways willdominate)


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Tetrahedral carbon (1)

All exo-Tet cyclisations are favoured

X

Y

n

X l p ir Ov rl p wit C- W*Att ck t 180 l c ccur

H2NBr1

2 3

3-exo-Tet


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Tetrahedral carbon (2) Why all endo-Tet cyclisations are disfavoured?

SO

S

O O

O

O

NaH

SO

S

O O

O

O

SO

S

O O

O

O

S O

S

O O

O

O

6- - t ?

6- - t Di f av ur : R acti clu iv l i t r l cular


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Trigonal Carbon (1)

Why all exo-Trig cyclisations are favoured?

O

H

OH

O1

2

3 4

5

5-exo-Trig

X n

Y

X lo e pair

Overlap wit C= T*Attack at 109 angl p ibl


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Trigonal Carbon (2)

Example of disfavoured 5-endo-Trig

O

O

XBase

O

O

5-endo-Trig

H

OH

OH

OH

O

H

O

HOH

5-e o-Trig


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Trigonal Carbon (3)

OH

OMe

O

Base

O

OMe

O

5-endo- rig

O

OMe

O

1

2

3

4

5

5

1

2

3

4

5 0%

OH OX

Base

5-endo- rig

Disfavouredandnot observed

OMe

O

OMe

O

5-endo-Trig versus 5-exo-Trig

5-exo- rig1

2

3

4

O O

5

100%


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Trigonal Carbon (4)

5-endo-Trig exceptions :

SH

CO2Me

S

CO2MeBaseSe ond ro element

-S ond longerem ty or ital 3d of S mayintera t ith - T or ital

isfa o red t ossi le

5-endo-Trig

- .43 ngstrm

-S . 2 ngstrm

R

R

O(CH2OH)2

O

OR

R

R R

HO O

OHH

- H2O

R

R

O

OH

5-endo-Trigisfa o red

H

R R

H2O O

OH

5-exo-TrigFa o red


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Trigonal Carbon (5) 5-endo-Trig versus 5-exo-Trig; Nitrogen analogue

MeO2C CO2Me

NH2 HN

MeO2C CO2Me

1

2

34

51

2

3

4

5

X

HN

O

MeO2C

5-endo-Trig%

5-exo-Trig%

1

2

3

45

ontrol ex eriment

CO2Me

PhCH2NH2Ph

HN

CO2Me

HN Ph

1 %%

O


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Trigonal Carbon (6)

5-endo-Trig versus 5-exo-Trig; Nitrogenanalogue (MO explanation)

N

O

OMeH

H

Bad alignment

N lone air an not rea hT* or ital of Mi hael a e tor

nitz angle atta not ossi le

N

HH

O

OMe

Too far a ay


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Digonal carbon

All endo-Dig cyclizations are favoured

O

O

Ar1

2

3

4 5

5-endo- ig

O

OT* ina essi le

ela ossi le in thelane of the ring

Ar

3- and 4-exo-Dig cyclisations are disfavoured

-X -XY

3-exo- ig 4-exo- ig

Y

12

3 1

2 3

4

N le hile an not atta ith the req ired 2 angle

x x


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Intramolecular Alkylations of

Ketone Enolates (1)

-O O

+ -(Enolendo)-Exo- et

Endocyclic alkylations

Exoclyclic alkylations

+ -

-OO

(Enolexo)-Exo- et

6- to 7- membere RC

Favoured 3- to 5- membere RC

Disfa oure

3- to 7- membere RC

Favoured


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Intramolecular Aldol

Condensations (1)

-O O

(Enolendo)-Exo- rig

Y-

-O Y O

(Enolexo)-Exo- rig

Y-

Endocyclic reactions

Exoclyclic reactions

3- to 7- membered RCFavoured

3- to 5- membered RC

Disfavoured 6- to 7- membered RCFavoured


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RESTRICCIONES

ESTERE

OELE

CTRON

ICA

S.

O

Y

O

Y

C alkylatio sC alkylatio s

180 atta

109 atta

Intramolecular alkylationsof ketone enolates

Intramolecular aldolcondensations

Oalkylatio s Oalkylatio s


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Ketone Enolates (1) Why 5-(Enolendo)-exo-tet disfavoured?

O

Br

O O

Br

M

t-BuOM

O

> 70% 0%

5-exo-Tet 5-(enolendo)-exo-tet

OOO

MX X

M


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Ketone Enolates (2) Why 6-(enolendo)-exo-tet favoured?

BrOO Br

M OO

>95% 0%

t-BuOM

6-(enolendo)-exo-tet

6-exo-Tet

XOM Possible because of extra bond lengt


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Condensations (2)

O

O

O O

O

O

O

O

O

+5-( nolendo)-

exo-trig

6-( nolendo)-

exo-trig

Statistics : 4 possibilities to form a 5 membered ring2 possibilities to form a 6 membered ring

Previsions : 6 membered ring would be predominant or exclusive

6-(enolendo)-exo-trig versus 5-(enolendo)-exo-trig


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Condensations (3)

O

O

O O

O

1 KOH

MeOH


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Baldwin Rules in Harrity Group (1)

RCo2(CO)6

O

RZ

RELewis Acid

RCo2(CO)6

ORE R

Z

OLA

RE

RZ

H

R

Co2(CO)6 OLA

RE

RZ

H

Co(CO)3

Co(CO)3

R

6-(enolendo)-exo-trig

Formation of cyclohexanones :


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Baldwin Rules in Harrity Group(2)

R1 Co2(CO)6

OR2

Le is id

R1

OLA H

H

Co(CO)3

Co(CO)3

R1

4-(enolexo)-exo-trig

R2

O

Co2(CO)6

R2

OLA H

R2

R1

Co2(CO)6

Formation of cyclobutane ketones :

6-exo- rig


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Conclusion

Only give information about whether processes arefavoured or disfavoured and not allowed andforbidden.

Nucleophilic RC feasibility strongly depends on ringsize, geometry of reacting atom and exo or endonature of reaction.

Structural modification can dramatically affect the

cyclization mode.

If favoured trajectory of attack valid, then reactionwill follow the Baldwins rules.


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Summary (1)

Size Exo Endo

Tet Trig Dig Tet Trig Dig

3 X X

4 X X

5 X X

6 X

7


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Summary (2)

Exo-Tet Exo-Trig

Size enolendo enolexo enolendo enolexo

3 X X

4 X X

5 X X

6

7


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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.

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