1

Cyclobutanes in Catalysis

YuLiu Du2013.6.8

2

▶ Introduction

▶ Ring Expansion through 1,2-Carbon shift

▶ Metal-Catalyzed Activation of C-C Bond

▶ Asymmetric Baeyer-Villiger Reation

▶ Conclusion

3

▶ Introduction

▶ Comparison of the strain energies and properties of small rings

27.5 26.7 25.4

Me

18.2

MeMe

7.4

Ring strain[kcal mol-1]

▶ Properties of Cyclobutane

O O

more stable

1. Less ring strain than Cyclopropanone, but still strong enough when liberated to enable and accelerates ring expansion or ring cleavage reactions.

2. More stable than Cyclopropanone.

4

▶ Ring Expansion through 1,2-Carbon shift

▶ Organocatalytic Rearrangements

O

R1 OH

n

10 mol% L*

0-23 ℃

O

R1 O

n

H

OP

OO

O

*

OR1

nO

51-98%74-98%ee

Trip

Trip

O

OP

O

OX X= H or Ag

Q. W. Zhang, C. A. Fan, H. J. Zhang, Y. Q. Tu, Y. M. Zhao, P. Gu, Z. M. Chen, Angew. Chem. Int. Ed. 2009, 48, 8572-8574.

5

▶O

R3

OH

R2 R1

20 mol% L*

40 mol%

Ph CO2H

NHBoc

O

R3O

R1R2

57-95% yield77-97% ee

N

OH

NH2

N

L*

E. Zhang, C. A. Fan, Y. Q. Tu, F. M. Zhang, Y. L. Song, J. Am. Chem. Soc. 2009, 131, 14626-14627.

R3

R4

R2

OH

R1[X] R3

R4

R2

OR1

HXR3

R4

R1

X

OR2

1,2-carbon migration in semipinacol rearrangement

R3R2

OH

R1

R4

O

R5R6NHR3

R2

OR1

H

N

R4

R6R5

R3

R1

OR2

O

R4

semipinacol-type 1,2-carbon migration and iminium catalysis in vinylogous -ketol rearrangement

X= P,NTs, NPhth, F+, Cl+, Br+, I+

6

▶ Lewis Acid Mediated Ring Opening

R2

N2R1+

O5-10 mol% Sc(OTf)3

toluene, 23℃

R1

R2

O

34-98%

R1, R2 = H, arkyl, arylO

LA

R1

R2N2

D. C. Moebius, J. S. Kingsbury, J. Am. Chem. Soc. 2009, 131, 878 -879

H

N2TMS+

O

Me

Ph

MePh

OTMS

MePh

OTMS

10 mol% Sc(hfac)3

10 mol% Sc(OTf)3 dilute HCl MePh

O

J. A. Dabrowski, D. C. Moebius, A. J. Wommack, A. F. Kornahrens, J. S. Kingsbury, Org. Lett. 2010, 12, 3598-3601

7

▶[4+2] cycloaddition reactionR1

CO2Me

CO2Me+

H R2

O2 mol% Sc(OTf)3

DCM, 23 ℃

R1, R2 = aryl, vinyl

OR1 R2

CO2Me

CO2Me

up to 93%dr 99:1

R

OMe

OMe

O

OLA

A. T. Parsons, J. S. Johnson, J. Am. Chem. Soc. 2009, 131, 14202-14203

CO2MeMeO2C

Ph

1.Co2(CO)8, DCM, r.t.

2.RCHO, Sc(OTf)3 4Å MS, DCM, r.t.

Ph

Co(CO)3(OC)3Co

OH

CO2MeCO2Me

HR

E. A. Allart, S. D. R. Christie, G. J. Pritchard, M. R. J. Elsegood, Chem. Commun. 2009, 7339-7341.

8

▶Proposed mechanism for the cycloaddition with electron rich aldehydes

Ph

Co

CO2Me

CO2Me

(CO)3O

OMe

CH2O2Me

CO2Me

O

OMe

CO2Me

O

MeO2COMe

O

MeO2CCO2Me

OMe

Ph

Co(CO)3

Ph

Co(CO)3

Ph

Co(CO)3

Ph CO2MeCO2Me

Co(CO)3(OC)3Co

Ph

Co(CO)3(OC)3Co

CO2MeCO2Me

OCO2Me

▶Proposed mechanism for the cycloaddition with electron poor aldehydes

9

▶

CO2Et

CO2EtR1O

R2

H

R3NPh

HR4R4 H

O

10 mol% Yb(OTf)3

NR3

R2

Ph

R4

CO2Et

CO2Et

42-86%

O R4

CO2Et

CO2Et

R3

R1O

R2

51-89%

10 mol% Yb(OTf)3

a) M. M. A. R. Moustafa, B. L. Pagenkopf, Org. Lett. 2010, 12,4732-4735; b) M. M. A. R. Moustafa, A. C. Stevens, B. P. Machin,B. L. Pagenkopf, Org. Lett.

2010, 12, 4736-4738.

▶ Transition-Metal-Catalyzed Ring Expansion

R

5 mol% PdCl2CuCl2, O2,H2O

benzene, 0℃R

OH

[Pd]O

RR= H, CN

CH2N(H)COMe 65-82%

P. Boontanonda, R. Grigg, J. Chem. Soc. Chem. Commun. 1977, 583-584.

Wacker-type reaction

10

▶ PdX2L2

R

OH

R

OH

PdX2L

OH

PdXL

R

+ L

O

R

+ HPdXL2

O

R

16-67%

G. R. Clark, S. Thiensathit, Tetrahedron Lett. 1985, 26, 2503-2506.

▶ Application in total synthesis

OMe

H

H

10 mol%PdCl2(CH3CN)2

DDQTHF, reflux

H

H

O

H

H

ventricosene70%

S. G. Sethofer, S. T. Staben, O. Y. Hung, F. D. Toste, Org. Lett. 2008, 10, 4315-4318.

11

R

Me

R

Me

H

OPd(OAc)2Ag2CO3

toluene/DMSO100℃

11 examples17 to 66% yield

▶

R

Me

=R

H

OH

Me

R

H

OH

Me

Pd

R

H

O

Me

H

Pd

R

Me

H

OPd

R

Me

H

O

A. Schweinitz, A. Chtchemelinine, A. Orellana, Org. Lett. 2011, 13, 232-235.

12

▶ Palladium(0)-Catalyzed Ring Expansion

OH

R [Pd]

Wagner-Meerwein shiftO

R

•HO

I Pd(0)

L

HO

PdLnXO O

63%

M. Yoshida, H. Nemoto, M. Ihara, Tetrahedron Lett. 1999, 40, 8583-8586.

▶ Wagner-Meerwein shift via hydropalladation reaction of electron-rich alkoxy allenes OH

•

OR1

2.5 mol% Pd2(dba)3.CHCl3

7.5 mol%(R,R)-Ligand

10% PhCO2H, 10% Et3NDCE

O

R2

R2

R2

R2

OR1

PdLn*HA

A

OH•

OR1R2

R2H PdLn

*

O

OR1R2

R2PdLn

*

PdLn*

up to 95% ee

A HA

B. M. Trost, J. Xie, J. Am. Chem. Soc. 2006, 128, 6044-6045.

Ph Ph

NH HNOO

PPh2Ph2P

13

HO

+ H+

-H2O

H

- H+

▶ TIPS: Wagner-Meerwein Rearrangement

a) Wagner, G. J. Russ. Phys. Chem. Soc. 1899, 31, 690.b) Hans Meerwein. Über den Reaktionsmechanismus der Umwandlung von Borneol in Camphen; [Dritte Mitteilung über Pinakolinumlagerungen.]. Justus Liebig’s Annalen der Chemie. 1914, 405: 129–175.

R3

R1

R2

X

R4

H

protic acid or lewis acid

R3

R1

R2

H

R4R1

R2R3

R4

H[1,2]-shift

- H R2

R1 R4

R3

Nuc R1

R2R3

R4

H

Nuc

▶ General scheme for Wagner-Meerwein Rearrangement

14

▶ Reaction involves a regioselective carbopalladation of alkynes

Pd0R1 I (R1= aryl, vinyl)

R1 Pd I

OH

R3

R2

OH

R2

R1

R3

Pd I

PdO

R2

R3 R1

O R3

R1

R2

10 mol%

23-74%Pd(OAc)2

a) R. C. Larock, C. K. Reddy, Org. Lett. 2000, 2, 3325-3327;b) R. C. Larock, C. K. Reddy, J. Org. Chem. 2002, 67, 2027-2033.

15

▶ Ruthenium-Catalyzed Ring Expansion

OH

R2

Ru(MeCN)3 PF6

(10 mol%)

R1 OH

•

+ R2

O

R2= H, Me

[Ru] O

R2O Ru

O

R2

H

R1

O

O

R2

R1

65-90%d.r.<2:1

M. Yoshida, K. Sugimoto, M. Ihara, Tetrahedron Lett. 2001, 42, 3877-3880

▶ Gold-Catalyzed Ring Expansion

OHR2

R1

2 mol % [(p-CF3C6H4)3P]AuCl2 mol% AgSbF6

OHR2

R1

[Au]

O

R1

R2

66-82%

J. P. Markham, S. T. Staben, F. D. Toste, J. Am. Chem. Soc. 2005, 127, 9708-9709.

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▶ Metal-Catalyzed Activation of C-C Bond

▶ Insertion into the Acyl-Carbon Bond of Cyclobutanones

H

HPh

O 5 mol% [RhCl(cod)]210 mol% dppe

50 atm H2toluene, 140℃

H

HPh

[Rh]

O

Me

OH

Ph

87%

M. Murakami, H. Amii, Y. Ito, Nature, 1994, 370, 540-541.

O

Bn Bn

5 mol% [Rh(cod)(dppb)]BF4

xylene, reflux

[Rh]Bn

Bn

CO

BnBn

99%

The wider P-Rh-P angle with dppb may cause larger steric repulsions to favor a four-membered rhodacycle rather than a five-membered one.

a) M. Murakami, T. Itahashi, H. Amii, K. Takahashi, Y. Ito, J. Am. Chem. Soc. 1998, 120, 9949-9950;

b) M. Murakami, H. Amii, K. Shigeto, Y. Ito, J. Am. Chem. Soc. 1996, 118, 8285-8290.

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▶ O HO 5 mol% [Rh(cod)2]BF412 mol% PCyPh2

CO, xylene, 100℃

[Rh] OH

OO

O

[Rh]

O

O

86%

a

Rhodacyclopentanone can be intercepted by an adjacent phenolic hydroxyl group.

CO atmosphere is performed to suppress the concurrent decarbonylation of a.

M. Murakami, T. Tsuruta, Y. Ito, Angew. Chem. Int. Ed. 2000, 39, 2484-2486.

O

5 mol% [Rh(nhd)dppp]PF6

BHT, xylene, 135℃

Rh

O RhO

O

M. Murakami, T. Itahashi, Y. Ito, J. Am. Chem. Soc. 2002, 124, 13976-13977

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▶ β-Carbon Elimination from tert-CyclobutanolatesO

HO R

[M] R

[M] OR'

- R'OH

[M]O R -carbon elimination

[M]

R

Ofurther

reactions

▶ Intermolecular 1,2-addition of aryl rhodium species

O

R

5 mol% [Rh(acac)(C2H4)2]10 mol% PtBu3

CsCO3, dioxane, 100℃

R O

Ar+ ArB(OH)2

39-95%

T. Matsuda, M. Makino, M. Murakami, Org. Lett. 2004, 6, 1257-1259.

19

▶ Proposed mechanism

[Rh] Ar

O

Ar

O [Rh]

Ar

O H

H+

Ar[Rh]

O

H

Ar

O

[Rh]HAr

O

[Rh]

OH

Ar

[Rh]

ArB(OH)2

O

Ar

20

▶ Intramolecular 1,2-addition

B(pin)

RO

5 mol% [RhCl(CH2=CH2)2]210 mol% dppb

0.5 equiv K3PO4dioxane-H2O(20:1), 100℃, 6h

R

RhO

transmetalation

addition

R

ORh

-carbonelimination

RRh

O

RMe

O

*

81-96%79-95% ee

O

O

O

O

PPh2

PPh2

B(Pin)=O

BO

T. Matsuda, M. Shigeno, M. Makino, M. Murakami, Org. Lett. 2006, 8, 3379-3381.

OH

RO

R

ORh OO ORh O O

Rh

O O

R

R Me7mol% [Rh(OH)(cod)]2

16 mol% (R)-Tol-BINAP

toluene, 23℃ 68-92%77-95% ee

P(p-Tol)2

P(p-Tol)2

enantioselective carbon elimination

T. Matsuda, M. Shigeno, M. Murakami, J. Am. Chem. Soc. 2007, 129, 12086-12087.

21

Ni0

O

R1 R2

+

R3

R3

O

R1 R2

R3

R3

Ni0

ONiII

R3 R3

R1

R2

NiII

R3

R3

O

R1

R2

O

R3

R3R1

R2

47-97%

▶ Formation of Nickel Cyclobutanolates by Cycloaddtion

M. Murakami, S. Ashida, T. Matsuda, J. Am. Chem. Soc. 2005, 127, 6932-6933.

22

O

R1 R2

+

E E

R' R' 10 mol% Ni(cod)220 mol% PnBu3

toluene, 100℃

O

R2

R1

R'R'

E E

E

E

R'

R'

Ni

R1 R2

ONi

E

E

R'

R'R1 R2

O NiO

R'

R'

E

E

R2

R1

68-91%

▶ [4+2+2] Cycloaddtion with diynes

M. Murakami, S. Ashida, T. Matsuda, J. Am. Chem. Soc. 2006, 128, 2166-2167.

23

R1

O

R2

R3

10 mol% Ni(cod)220 mol% PCy3

toluene, 100℃

R1 O

R2

R3

[Ni]

R1

O

R2

R3

[Ni] R1

R2

O[Ni]

R3

R1

R2

[Ni]

R3

O

-[Ni]

40-91%

▶ Intramolecular Nickel-Catalyzed cycloaddition

M. Murakami, S. Ashida, Chem. Commun. 2006, 4599-4601.

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▶ b-Carbon Elimination from tert-Cyclobutanols

R2

H

OH

R1

5 mol% Pd(OAc)210 mol% L*, ArBr

CsCO3, toluene80℃

R1

O[Pd]

Ar

HR2

R1

OAr

HR2

74-99%36-95% ee

Fe PPh2

N

H Me

T. Nishimura, S. Matsumura, Y. Maeda, S. Uemura, J. Am. Chem. Soc. 2003, 125, 8862-8869

▶ b-Carbon Elimination from iminyl Palladium(II) complexes

NOBz

R1 R2

2.5 mol% Pd2(dba)37.5 mol% rac-binap

K2CO3, THF, reflux

N[Pd]

R1 R2

-Celimination

R1 R2

CN [Pd]

R1 R2

CN [Pd] [Pd]NC

R1 R2

reductiveelimination

R1, R2 = H

NC

R1 R2

R1

CN-H

elimination

R2=H

a) T. Nishimura, S. Uemura, J. Am. Chem. Soc. 2000, 122, 12049-12050; b) T. Nishimura, Y. Nishiguchi, Y. Maeda, S. Uemura, J. Org. Chem. 2004, 69, 5342-5347;c) T. Nishimura, T. Yoshinaka, Y. Nishiguchi, Y. Maeda, S. Uemura, Org. Lett. 2005, 7, 2425-2427.

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▶ Asymmetric Baeyer-Villiger Reation

▶ Enzymatic BV reaction

O

O2 +BVMO

cat. NADPH

EDTA

light

decomposition

phosphite

PTDH

phosphate

O +

O

+ H2O

55% (81% ee) 45% (99% ee)

D. E. Torres Pazmino, R. Snajdrova, B. J. Baas, M. Ghobrial, M. D. Mihovilovic, M. Fraaije, Angew. Chem. Int. Ed. 2008, 47, 2275-2278.

BVMO: Baeyer-Villiger monooxygenases

26

O

R

20 mol% Me2AlCl, 20 mol% L1*cumene hydroperoxide

5 mol% L2*, H2O2.CO(NH2)2

84-96%, 34-84% ee

43-68%, 81-87% ee

5 mol% (PhCN)2PdCl2, 10 mol% AgSbF6

5 mol% L3*,H2O2.CO(NH2)2

65-94%, 60-83% ee

O

O

R*

▶ [4+2+2] Cycloaddtion with diynes

Ph

Ph

OH

OH

N

OPh

N

PhO

Zr

Y

Y

Y=PhO

L1vanol

N

PPh2

iPr

L2 L3

a) C. Bolm, J.-C. Frison, Y. Zhang,W. D. Wulff, Synlett 2004, 1619-1621;b) K.Ito, A. Ishii, T. Kuroda, T. Katsuki, Synlett 2003, 643-646;c) A. V. Malkov, F. Friscourt, M. Bell, M. E. Swarbick, P. Kočovský, J. Org. Chem. 2008, 73, 3996-4003.

27

O

R

10 mol% L*, 25 mol% AcONa

H2O2(1.5 equiv) O

O

R*

R= aryl 17-67%61-74% ee

N

N

N

HNN

MeO

O

Et

NEt

N

NMe O

O

▶ Organocatalytic BV Reactions

Y. Imada, H. Iida, S. Murahashi, T. Naota, Angew. Chem. Int. Ed. 2005, 44, 1704-1706.

O

R1 R2

+H2O2O

PO

O O*

H

H OO

H

O

R1R2

OP

O

O O*

H

O

O

R1

R2*

-H2OO

PO

O O

*H

H O

O

R1R2

H

O

O

OP

O

OH

X

X

X= pyren-1-yl

a) S. Xu, Z. Wang, X. Zhang, X. Zhang, K. Ding, Angew. Chem. Int. Ed. 2008, 47, 2840-2843;b) S. Xu, Z. Wang, Y. Li, X. Zhang, H. Wang, K. Ding, Chem. Eur. J. 2010, 16, 3021-3035.

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▶ Conclusion

▶ In this presentation, recent advance uses of four-membered rings as potent substrates in catalysis have been delighted.

▶ Transition-metal catalysts, mainly rhodium and palladium complexes, have been successfully used for insertions into the acyl-carbon bond of cyclobutanones and for b-carbon eliminations of tert-cyclobutanols.

▶ These methods provide access to synthetically versatile building blocks and are complementary to traditional approaches. This kind of reaction methods of cyclobutanones will be applied more in natural products synthesis, and will gain a good advance.