1

Problem SetFebruary, 2nd, 2010

Vincent N. G. Lindsay

Frontier Molecular Orbitals and Pericyclic Reactions

S S S S

UV

Vis

Cyril Nicolas

2

Problem 1

In a “recent” paper (e.g., Org. Lett. 2003, 5, 2619) Uemura and co-workers have reported the preparation of furan-containing sulfide derivatives. In the study, they observed that product 1 was thermally labile, and gradually isomerized to give another structural form (2) at ambient temperature. The mechanism proposed, was a [3,5] sigmatropic rearrangement. Provide an FMO analysis that illustrates why, this is not a plausible mechanism. Also, provide a mechanism for this rearrangement that would be more consistent with the orbital symmetry rules.

O

PhSMeOOC

O

PhSCOOMe1 2

[3,5] supra-supra not allowed

0 node

1 node

2 nodes

0 node

1 node

Migration supra supra

OMeOOC

PhSO

PhSMeOOC

node

if [3,5] sigmatropic rearrangement

3

Problem 1

Migration supra supra

()

Migration supra supra

()

O

PhSMeOOC

O

PhSCOOMe1 2

[3,3] supra supra allowed

0 node

1 node

0 node

1 node

OMeOOC

PhS

O

SPhMeOOC

if two consecutives

[3,3] sigmatropicrearrangements

OMeOOC

PhS

4

Problem 2

Me

Me Me

300°C

Me Me

Me

Berson and co-workers have studied the following thermal isomerization (J. Am. Chem. Soc. 1966, 88, 2494). Propose a rationale for these results using three-dimensional drawings and FMO analysis.

0 node

1 node

2 nodes

1

2

3

5

Problem 2

Me

Me Me

300°C

Me Me

Me

Berson and co-workers have studied the following thermal isomerization (J. Am. Chem. Soc. 1966, 88, 2494). Propose a rationale for these results using three-dimensional drawings and FMO analysis.

Me

Me Me

disrotatory ring closure

retention at the migrating carbon

MeMeMe

supra supra

1,5-migrationMeMe

Me

disrotatory ring opening

Me

Me

Me

0 node

1 node

2 nodes

1

2

3

6

Problem 2

Me

Me Me

300°C

Me Me

Me

Me

Me Me

disrotatory ring closure

retention at the migrating carbon

MeMeMe

supra supra

1,5-migrationMeMe

Me

disrotatory ring opening

MeMe

Me

MeMe

Me0 node

1 node

2 nodes

1

2

3

Me

Me

Me

Berson and co-workers have studied the following thermal isomerization (J. Am. Chem. Soc. 1966, 88, 2494). Propose a rationale for these results using three-dimensional drawings and FMO analysis.

7

Problem 2

Me

Me Me

300°C

Me Me

Me

Me

Me Me

disrotatory ring closure

retention at the migrating carbon

MeMeMe

supra supra

1,5-migrationMeMe

Me

disrotatory ring opening

Me

Me

Me MeMe

Me

LUMO

HOMO

2

1

Berson and co-workers have studied the following thermal isomerization (J. Am. Chem. Soc. 1966, 88, 2494). Propose a rationale for these results using three-dimensional drawings and FMO analysis.

MeMe

Me

MeMe

Me

8

Problem 3

Upon irradiation and subsequent work-up, 3 undergoes two sequential reactions to give 4 as the only product (J. Chem. Soc. Perkin Trans. 1973, 505). Provide a mechanistic rationale for the transformation and predict the final stereochemistry of the product. Also, explain why the thermal reaction would probably afford a totally different result. For this, you should take into consideration frontier molecular orbital diagrams.

0 node

1 node

2 nodes

1

2

3

3 nodes

4

O

NMe

6 electrons electrocyclization

conrotatory

NO Me

O

NMe

HH

h

O

NMe

O

NMe

hH

H

3 4

9

Problem 3

O

NMe

6 electrons electrocyclization

conrotatory

NO Me

O

NMe

HH

h

O

NMe

O

NMe

hH

H

3 4

0 node

1 node

2 nodes

3 nodes

4

3

2

1

1,5 H shiftsuprafacial

NO Me

O

NMe

HH

H

supra supra

Geometry of the intermediate does not permit antarafacial light induced 1,5 shift

10

Problem 4

The acetylene alkoxide (ynolate) 5 reacts with para-substituted acetophenones (6) to give, respectively (E) and (Z) unsaturated acids 7 and 8. Interestingly, along the experiment, it was determined that the (E):(Z) ratio strongly depends on the substituent on the aromatic ring (vide infra). Using Kékulé-Couper drawings and FMO theory provide a mechanism that could account for both, the overall transformation and stereoelectronic issues.

O

nBu

OLi

R

1. THF, r.t.

2. Acid quenchMe

R

nBu CO2H

Me

R

HO2C nBu

++

R Ratio (7:8)

>99:1

H 86:14

NO2 40:60

5 6 7 8

Me2N

11

Problem 4

Me

O

nBu

OLi

R

1. THF, r.t.

2. Acid quenchMe

R

nBu CO2H

Me

R

HO2C nBu

++

5 6 7 8

Me

R

O

CnBu

O

Me

R

OnBu

O R

nBuO

OMe

R

nBuO

OMe

nBu

OO

Me

R

7

8

path a

path b

When stereoelectronics are dominant R = NO2

When sterics are dominant R = H, NMe2

4 electrons electrocyclization = conrotatory under thermal conditions

phenyl group out

phenyl group in

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Problem 5

Hsung et al. have reported the diastereoselective reaction shown below (Org. Lett. 2000, 2, 1161). While there is a mechanistic ambiguity associated with this process, the authors have suggested that the stereochemical-determinig step would probably proceed in a concerted pericyclic manner. Using FMO analysis and 3D drawings propose a concise mechanism which is consistent with the sense of asymmetric induction observed in the reaction.

heat ~ 100 °C

piperidine

O

NH

PhPh

OTBS

R

H

N+

O

N

PhPh

OTBS

R

O

N

PhPh

OTBS

R+

diastereoselection 9:10 > 10:1

9 10

O N

N R

Ph

OTBS

Ph

O N

N R

Ph

OTBS

Ph

HO

N R

PhRL

Acid catalyzed enolization E1CB

13

O

N R

PhRL

NR

O

RL

HPh

NR

O

RL

HPh

N

O

RLPh

HR

H

NR

O

RL

HPh

N

ORL

PhH

H

R

A(1,3) strain

minor product

major product

0 node

1 node

2 nodes

1

2

3

Problem 5

2 possible disrotatory

ring-closures

Steric interactions