Stevens, Sommelet-Hauser and Related Rearrangements

Literature PresentationApril 4th, 2011

Presented byLouis-Philippe Beaulieu

Gatineau (Aylmer), Qc

2

1842

2011

Stevens and Sommelet Biographical Sketches

3

Marcel Sommelet (1877−1952) wasborn in Langes, France. He received his Ph.D. In 1906 at Paris where he joined theFaculté de Pharmacie after WWI and became the chair of organic chemistry in 1934.

Thomas Stevens Stevens (1900−2000) was born in Renfrew, Scotland, UK. He received his Ph.D at Oxon, became University Assistant at Glasgow in 1925 and Lecturer in 1933. He is also known for the McFadyen-Stevens synthesis ofaldehydes and the Bamford-Stevens elimination reaction, which converts ketones to alkenes.

Program

4

• Biographical Sketches of Stevens and Sommelet

• The Stevens Rearrangement: Seminal Discovery

Mechanistic Studies

• The Sommelet-Hauser Rearrangement: Seminal Discovery

Mechanistic Studies

• Competition Between [1,2] and [2,3] Pathways

• Different Methods for Ylide Generation

• Asymmetric Versions: C to C Chirality Transfer

C to N Chirality Transfer

Strictly Enantioselective Stevens Rearrangement

The Stevens Rearrangement: Seminal Discovery

5T. S. Stevens, E. M. Creighton, A. B. Gordon, M. MacNicol, J. Chem. Soc., 1928, 3193.

N

O

Ph

PhBr

Na/Hg

H2OPh

O

N

Ph

N

O

Ph

PhBr

Zn dust

NO2

NO2O2N

HN

Ph

OH

O

NO2

NO2O2N

O

OO

PhN

Ph

Br

Intramolecular Nature of the Rearrangement

6T. S. Stevens, J. Chem. Soc., 1930, 2107.R. A. W. Johnstone, T. S. Stevens, J. Chem. Soc. 1955, 4487.

O

PhN

Br

O

N

PhBr

+NaOEt

EtOH

Br

NPh

O

NO

PhBr

+

Br

Br

O

PhN

O

N14CH2

PhBr

+NaOEt

EtOH

NPh

O

H214C

NO

PhBr

+

Br

Br

PhPh

373 counts min-1 cm-2 403 counts min-1 cm-2

13 counts min-1 cm-2

Background:

16 counts min-1 cm-2

Retention of Stereogenic Information

7J. H. Brewster, M. W. Kline, J. Am. Chem. Soc. 1952, 74, 5179.

O

PhBr

N

PhH

N

H

PhH

O

Ph

ZnHOAc

H

H

PhH

O

Ph

NH2OH

H

H

PhH

N

Ph

OHSOCl2

H

H

PhH

O

NH

Ph H

H

PhH

O

HO

97% ee

NH2

PhH

CH2OHCO2H N

PhHPh

O

Br

98% ee

NaOH aq.

H2SO4 conc.

Involvement of a Nitrogen Ylide

8

R. W. Jemison, S. Mageswaran, W. D. Ollis, S. E. Potter, A. J. Pretty, I. O. Sutherland, Y. Thebtaranonth,J. Chem. Soc., Chem. Commun. 1970, 1201.T. Thomson, T. S. Stevens, J. Chem. Soc. 1932, 55.J. L. Dunn, T. S. Stevens, J. Chem. Soc. 1932, 1926.

Ph

O

N

ArBr NaOH aq.

Ph

O

N

Ar

0 CPh

O

N

Ar

50 C

1 2 3

Rate of reaction: p-NO2C6H4 p-HalC6H4 p-MeC6H4 p-OMeC6H4

Ph

O

N

PhBr NaOH aq.

Ph

O

N

Ph

0 CPh

O

N

Ph

50 C

1 2 3

Quant.

Ion Pair Mechanism vs. Concerted Intramolecular Displacement

9

T. Thomson, T. S. Stevens, J. Chem. Soc. 1932, 55.J. L. Dunn, T. S. Stevens, J. Chem. Soc. 1932, 1926.R. Hoffmann, R. B. Woodward, Acc. Chem. Res. 1968, 1, 17.

Ph

O

N

PhBr

Ph

O

N

PhPh

O

N

PhOH-

Ph

O

N

Ph

Ph

O

N

PhBr

Ph

O

N

Ph

Ph

O

N

PhOH-

Chemically Induced Dynamic Nuclear Polarization (CIDNP) Mechanistic Study

10IUPAC Compendium of Chemical Terminology

CIDNP : Non-Boltzmann nuclear spin state distribution produced in thermal orphotochemical reactions, usually from colligation and diffusion, or disproportionationof radical pairs, and detected by NMR spectroscopy by enhanced absorption or emission signals.

OH CH3+ CH3OHColligation:

CH2CH3 + CH2CH3 CH2=CH2 + CH3CH3Disproportionation:

Chemically Induced Dynamic Nuclear Polarization (CIDNP) Mechanistic Study

11

IUPAC Compendium of Chemical TerminologyPavia, D. L.; Lampman, G. M.; Kriz, G. S. Introduction to Spectroscopy; Vondeling, J., Kiselica, S., Eds.; Thomson Learning, 2001; p. 108.

Nupper

Nlower= e E/kT = e h/kT

h = 6.624 x 10 34 Jsec (molecular gas constant)

k = 1.380 x 10 23 J/Kmolecule (Planck's constant)

T = absolute temperature (K)

Boltzmann Distribution of Nuclear Spins

CIDNP : Non-Boltzmann nuclear spin state distribution produced in thermal orphotochemical reactions, usually from colligation and diffusion, or disproportionationof radical pairs, and detected by NMR spectroscopy by enhanced absorption or emission signals.

DNP : results from transferring spin polarization from electrons to nuclei, thereby aligning thenuclear spins to the extent that electron spins are aligned.

Chemically Induced Dynamic Nuclear Polarization (CIDNP) Mechanistic Study

12A. R. Lepley, J. Am. Chem. Soc. 1969, 91, 1237.

PhN Ph

H

Ph N

Li

+

F

0.3 min

10 min

Ph N

NHC Ph

H

PhN

CH

PhPh

NCH

Ph

CH3

Product

Radical Pair Mechanistic Patway

13W. D. Ollis, M. Rey, I. O. Sutherland, J. Chem. Soc., Perkin Trans. 1 1983, 1009.

Radical Pair Mechanistic Patway

14W. D. Ollis, M. Rey, I. O. Sutherland, J. Chem. Soc., Perkin Trans. 1 1983, 1009.

Sommelet-Hauser Reaction: Seminal Discovery

15Sommelet, M. Compt. Rend. 1937, 205, 56.S. W. Kantor, C. R. Hauser, J. Am. Chem. Soc. 1951, 73, 4122.

N

Ph

OH

PCl5

hv, vacuum

Ph

N

N

Ph

I

NaNH2 (2.0 equiv)

Liq. NH3

Ph

N

88%

N

Ph

Br

HN

Ph

Br

OMe +MeOH

N

Ph

OHH2O,

N

Ph

OH + + Side product

Mechanistic Insight Through Intermediate Isolation/Trapping

16C. R. Hauser, D. N. Van Eenam, J. Am. Chem. Soc. 1957, 79, 5512.S. H. Pine, B. L. Sanchez, Tetrahedron Lett. 1969, 10, 1319.

N

n-BuLi (2.0 equiv)

Hexane, rt

NN

70%

n-BuLi

- LiH

n-C5H11

N + N + N

10% 45% 32%

Br

N

NaNH2 (2.0 equiv)

Liq. NH3

NN

70%

Br

Competition Between [1,2] and [2,3] Pathways

17E. Tayama, K. Takedachi, H. Iwamoto, E. Hasegawa, Tetrahedron 2010, 66, 9389.

Competition Between [1,2] and [2,3] Pathways

18E. Tayama, K. Takedachi, H. Iwamoto, E. Hasegawa, Tetrahedron 2010, 66, 9389.

Competition Between [1,2] and [2,3] Pathways

19

E. Tayama, K. Takedachi, H. Iwamoto, E. Hasegawa, Tetrahedron 2010, 66, 9389.G. Ghigo, S. Cagnina, A. Maranzana, G. Tonachini, J. Org. Chem. 2010, 75, 3608.Kürti, L.; Czakó, B. Strategic Applications of Named Reactions in Organic Synthesis; Hayhurst, J.; Marr, D., Eds.; Elsevier

Academic Press, 2005; p. 422.

[1,2] Stevens rearrangement

Favored in nonpolar organic solvents (ether, hexanes)and high temperatures

Sommelet-Hauser rearrangement

Favored in polar solvents(NH3, DMSO, HMPA)And low temperatures

Formation of intermediate SHI is significantly less endoergic (35 kcal mol-1) according to M05-2x DFT calculations

Base-Mediated Formation of Ylides: Some Drawbacks

20F. E. Ray, J. L. Farmer, J. Org. Chem. 1943, 08, 391.E. Vedejs, D. A. Engler, M. J. Mullins, The Journal of Organic Chemistry 1977, 42, 3109.

S R X+

X = Cl, BrR = alkyl, aryl, vinyl, carbonyl

S R

X

S R

S R + MeX

Base

O

OEtF3CO2SO

X O

OEtX

X = NR2, SRR = alkyl

OTf

Dealkylation

Base-Mediated Formation of Ylides: Some Drawbacks

21L. P. A. Fery, L. van Hove, Bull. Soc. Chim. Belg. 1960, 69, 79.C. L. Bumgardner, H.-B. Hsu, F. Afghahi, W. L. Roberts, S. T. Purrington, J. Org. Chem. 1979, 44, 2348.

O N

Ph

NaNH2 (2 equiv)

NH3, 29hO N

Ph

H2O/H+

HO N

Ph73%

NO

H

HPh

Br

Hoffmann Elimination

Regioselectivity of Ylide Generation

N CD3

X

NaNH2

NH3N CD3 N

CD3

N

CD3

N

CD3

58% 11%

Fluoride-Mediated Fromation of Ylides

22E. Vedejs, G. R. Martinez, J. Am. Chem. Soc. 1979, 101, 6452.

Ph S CO2Et

SiMe3

CsF

MeCNPh S CO2Et Ph S CO2Et

PhS CO2Et

PhCO2Et

SMe

81% 9%

Br

Direct Formation of Ylides from Diazo Compounds Under Metal Catalysis

23M. P. Doyle, W. H. Tamblyn, V. Bagheri, J. Org. Chem. 1981, 46, 5094.J. A. Vanecko, H. Wan, F. G. West, Tetrahedron 2006, 62, 1043.

X

N2

O

OEt

XO

OEtRh2(OAc)4

XO

OEt

X = SMe: 91% yieldX = NMe2: 60% yield

Asymmetric Versions: C to C Chirality Transfer

24S. Hanessian, M. Mauduit, Angew. Chem., Int. Ed. 2001, 40, 3810.

Asymmetric Versions: C to C Chirality Transfer

25S. Hanessian, M. Mauduit, Angew. Chem., Int. Ed. 2001, 40, 3810.

Asymmetric Versions: C to C Chirality Transfer

26S. Hanessian, M. Mauduit, Angew. Chem., Int. Ed. 2001, 40, 3810.

Asymmetric Versions: C to C Chirality Transfer

27S. Hanessian, M. Mauduit, Angew. Chem., Int. Ed. 2001, 40, 3810.

Asymmetric Versions: C to C Chirality Transfer

28S. Hanessian, C. Talbot, P. Saravanan, Synthesis 2006, 723.

Asymmetric Versions: C to C Chirality Transfer

29S. Hanessian, C. Talbot, P. Saravanan, Synthesis 2006, 723.

Asymmetric Versions: C to C Chirality Transfer

30S. Hanessian, C. Talbot, P. Saravanan, Synthesis 2006, 723.

Asymmetric Versions: C to C Chirality Transfer

31S. Hanessian, C. Talbot, P. Saravanan, Synthesis 2006, 723.

Asymmetric Versions: N to C Chirality Transfer

32K. W. Glaeske, F. G. West, Org. Lett. 1999, 1, 31.

Asymmetric Versions: N to C Chirality Transfer

33K. W. Glaeske, F. G. West, Org. Lett. 1999, 1, 31.

Asymmetric Versions: N to C Chirality Transfer

34E. Tayama, S. Nanbara, T. Nakai, Chem. Lett. 2006, 35, 478.

Asymmetric Versions: C to C Chirality Transfer

35I. G. Stara, I. Stary, M. Tichy, J. Zavada, V. Hanus, J. Am. Chem. Soc. 1994, 116, 5084.

Y X

Base Y Y+

(S) (R, 3R) (R, 3S)

1a-c 2a-c 3a-c

Asymmetric Versions: C to C Chirality Transfer

36I. G. Stara, I. Stary, M. Tichy, J. Zavada, V. Hanus, J. Am. Chem. Soc. 1994, 116, 5084.

Y X

Base Y Y+

(S) (R, 3R) (R, 3S)

1a-c 2a-c 3a-c

Strictly Enantioselective Stevens Rearrangement

37M.-H. GonAalves-Farbos, L. Vial, J. m. Lacour, Chem. Commun. 2008, 829.

Br

Br

N

Br

K2CO3

MeCN, 90 C

NH

71%

DCM/Acetone

(1.2 equiv)N

-5

70%

Strictly Enantioselective Stevens Rearrangement

38M.-H. GonAalves-Farbos, L. Vial, J. m. Lacour, Chem. Commun. 2008, 829.

P

N

N

NNP P

P

NMe2

NMe2

Me2N

NMe2

NMe2

NMe2

NMe2

P4-t-BuSchwesinger base

Me2N NMe2

Strictly Enantioselective Stevens Rearrangement

39M.-H. GonAalves-Farbos, L. Vial, J. m. Lacour, Chem. Commun. 2008, 829.