1 Single electron transfer reaction involving 1,3-dicarbonyl compounds and its synthetic...

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Single electron transfer reaction involving 1,3-dicarbonyl compounds

and its synthetic applications

Reporter: Jie Yu Oct. 31, 2009

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Introduction to the free-radical reaction

Intramolecular cyclization

Tandem annulations

Triple and higher cyzlizations

Asymmetric Induction

-hydroxylation with O2

Radical reactions of [60]fullerene

Oxidative addition

1,2-radical rearrangment

Synthetic applications

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In the propagation steps, the most popular way to control enantioselectivity has been the use of a chiral Lewis acid. The chiral Lewis acid can be used to bind to substrate or radical species and determine the approach of the other reacting component while accelerating the chiral pathway relative to the background reaction.

Sibi, M. P. Chem. Rev. 2003, 103, 3263

1. Introduction —Elementary Steps in Radical Reactions

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LmMn + C X + LmMn+1XC

LmMn + C X

LmMn+1

C X C + X-

X = leaving group; Lm = Ligand;M = transition metal, such as Ti(0-III) V(II), Cr(II), Co(I, II), Nb(IV), Ru(II)

1) Reductive process:

The metal acts as a reductant in this process and the carbon-centered radicals can be generated by an atom transfer or electron transfer from metal complex to the radical precursor. Such as pinacol coupling of dialdehyde using Ti(III) and Zn.

1. Introduction —Transition metal-promoted radical reaction

Iqbal, J. Chem. Rev. 1994, 94, 519

Transition metal-promoted reaction of carbon-centered radicals may be divided into two categories:

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1. Introduction —Transition metal-promoted radical reaction

C CXH

LmMn +

LmMn-1

C CXH

C CX

+ H

C ZLmMn +

LmMn-1

C + Z+

X = Hetero atom; Lm = Ligand;Z = Main group metal;M = Transition metal, such as Ti (IV), V(V), Mn(III), Fe(III), Co(III), Cu(II)

2) Oxidative process:

The reaction proceeds via an organometallic reagent which may lead to the carbon-centered radical on homolytic cleavage of carbon-metal bond.

Iqbal, J. Chem. Rev. 1994, 94, 519

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1. Introduction —Machanism of oxidation with Mn(III) involving -keto esters

-alkyl -keto ester:

-unsubstituted -keto ester:

1) A methyl group should slow down the formation of Mn(III) enolate, since it is electron donating and decreases the acidity of the -proton.

2) The methyl group should facilitate the oxidation since it will stabilize the radical.

Why?

Snider, B. B. Chem. Rev. 1996, 96, 339

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2. Intramolecular cyclization

Snider, B. B. Chem. Rev. 1996, 96, 339

different type of the dicarbonyl compounds:

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2. Intramolecular cyclization A. The formation of cycloalkanones

6-endo-cyclization (n=1) to give the product is the exclusive reaction if the proximal carbon is more highly substituted than the distal carbon

Snider, B. B. J. Org. Chem. 1988, 53, 2137

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The low yield is due to the further oxidation of the products. The cyclized radical is oxidized to a cation, which loses a proton to give alkene or reacts with solvent to give acetate.



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Snider, B. B. Tetrahedron 1995, 51, 12983


Snider, B. B. Org. Lett. 2004, 6, 1265

It can be trapped with azide and Mn(III) to give cyclic and bicyclic azides. Reduction of the azide gives bi- and tricyclic lactams.

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2. Intramolecular cyclization B. The formation of cycloalkanes


Rama Rao, A. V. Chem. Commun. 1989, 400

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2. Intramolecular cyclization B. The formation of cycloalkanes

Snider, B. B. Tetrahedron 2002, 58, 25

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Corey, E. J. J. Am. Chem. Soc. 1984, 106, 5384

Fristad, W. E. Tetrahedron Lett. 1985, 26, 3761

2. Intramolecular cyclization C. The formation of lactones & lactams

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2. Intramolecular cyclization C. The formation of lactones & lactams

Cossy, J. J. Org. Chem. 2000, 65, 7257

Cossy, J. Tetrahedron Lett. 1989, 30, 4531

Conditions: Mn(OAc)3, EtOH, K2CO3

Conditions: Mn(OAc)3, EtOH

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2. Intramolecular cyclization D. Additions to aromatic rings

CeIV = CAN; HX = MeOH

Cetterio, A. Synthesis, 1990, 142

N CO2HO

N CO2Et

CO2Et

O

Mn(OAc)3,AcOH, 80 oC

100% N CO2EtO

CO2Et

ketorolac

Muchowski, J. M. Can. J. Chem. 1992, 70, 1838

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3. Tandem annulationsA. Intramolecular

Snider, B. B. J. Am. Chem. Soc. 1990, 112, 2759Snider, B. B. J. Org. Chem. 1991, 56, 328

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3. Tandem annulationsA. Intramolecular

access to the core skeletons of Oroidin Dimers:

Chen, C. Angew. Chem. Int. Ed. 2006, 45, 4345

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3. Tandem annulationsB. Intermolecular

First Tandem Cyclization of Alkylenecyclopropanes

Huang, X. J. Org. Chem. 2004, 69, 5471

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Shi, M. J. Org. Chem. 2005, 70, 3859

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Further oxidized by a sencond equiv of CAN to the corresponding cation

Ruzziconi, R. Synth. Commun. 1988, 18, 1841Nair, V. J. Chem. Soc., Perkin Trans. 1 1995, 187

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3. Tandem annulationsC. Group-transfer reaction —— bromine atom

O

OEt

O

Br

R1R2

n

n = 1, R1 = R2 = Men = 2, R1= Et, R2 = Hn = 2, R1 = H, R2 = Etn = 2, R1 = R2 = Me

O

n

CO2Et

Br

R1

R2

Mg(ClO4)2, ligand,Et3B/O2, -78 oC

solvent

up to 94% ee

N

O

N

O

t-But-Bu ligand

O

OEt

O

Br

[Yb(OTf)3] (1.0 equiv)ligand (1.1 equiv)Et3B/O2, -78 oC

CO2Et

HCH3

O

Br

+

O

OEt

O

CH2Cl2

N

N

OO

N

Ph

Ph ligand

yield: 60%ee: 66% yield: 23%

Yang, D. Angew. Chem. Int. Ed. 2002, 41, 3014

Yang, D. J. Am. Chem. Soc. 2001, 123, 8612

The addition of molecular sieves led to reversed enantiofacial selectivity of the cyclization

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3. Tandem annulationsC. Group-transfer reaction —— chlorine atom

Yang, D. Org. Lett. 2006, 8, 5757

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O

OEt

O

SePh

Mg(ClO4)2, ligandtoluene, Et3B/O2

-78 oC, 4 A MS

OCO2Et

SePh N

O

N

O

t-But-Bu ligandup to 97% ee

Transition-state:

Yang, D. Angew. Chem. Int. Ed. 2006, 45, 255

3. Tandem annulationsC. Group-transfer reaction —— PhSe-group

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4. Triple and higher cyzlizations

Snider, B. B. J. Am. Chem. Soc. 1990, 112, 2759

Gonzalez, M. A. J. Org. Chem. 2007, 72, 7462

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5. Asymmetric Induction


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5. Asymmetric Induction

Snider, B. B. Tetrahedron Lett. 1992, 33, 5921.Snider, B. B. J. Org. Chem. 1993, 58, 7640

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CH2

Ph

Ph OO

Me

OH

RPh

Ph

MeCOCH2R+O2, Mn(OAc)n

n= 2 or 3

R = -COR', -CONR'R'', -CO2R', -SOR', -SO2R', -PO(OMe)2

Kurosawa, K. Bull. Chem.Soc. Jpn. 1991, 64, 3557Kurosawa, K. Bull. Chem.Soc. Jpn. 1992, 65, 1371Kurosawa, K. J. Org. Chem. 1993, 58, 4448

Ruveda, E. A. Tetrahedron 1990, 46, 4149

6. -hydroxylation with O2

Christoffers, J. J. Org. Chem. 1999, 64, 7668

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6. -hydroxylation with O2

use dioxygen as oxidant; the cerium salt can be considered as the optimal catalyst since it is non-toxic and inexpensive.

Christoffers, J. Eur. J. Org. Chem. 2003, 425Christoffers, J. Eur. J. Org. Chem. 2006, 2601Christoffers, J. Adv. Synth. Catal. 2004, 346, 143

O

CO2Me

MeO

O

CO2Me

MeO

OHCeCl3, iPrOH1 atm O2, 17h

80%

O

CO2Me

MeO

OH

(-)-kjellmanianone

29%, 99% ee

(a) Candida antarctica lipase B, toluene/phosphate buffer, 35-40 oC, 48 h

lipase, (a)

Christoffers, J. Chem. Eur. J. 2004, 10, 1042

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7. Radical reactions of [60]fullerene

Wang, G. W. Org. Biomol. Chem., 2006, 4, 2595

Wang, G. W. Org. Biomol. Chem., 2005, 3, 794

mechanism:

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OR

R'OO

OR'''

R''O

R

OR''

R'''

OR'OMn(OAc)3 (2.5 equiv)NaOAc(3 equiv), HOAc,Ar atm, 80 oC, 5 - 23 h

+41% - 73% yield

8. Oxidative addition

Perumal, P. T. J. Heterocyclic Chem. 2007, 44, 827

Wang, G. W. J. Org. Chem. 2008, 73, 7088

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9. 1,2-radical rearrangment

Nishino, H. J. Org. Chem. 2009, 74, 3978

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10. Synthetic applications

Helichrysum dendroideum

3, 4 was isolated from the leaves of Helichrysum dendroideum


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CH2

O

CO2Et

H

H

CH2

OEtO2C 1 2 (35%)

Mn(OAc)3, Cu(OAc)2

MeOH, 25 oC, 3h

CH2

CO2Et

O

CH2

CO2Et

O

Mn(III)

CH2

O

CO2Et

O

CO2Et

CH2

O

CO2Et

CH2

Cu(II)

Key step:

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Tripterygium wilfordii Hook F

OCH3

R

O

O

O

Ph

H

OCH3

R

O

O

O

Ph

H

OCH3

R

O

O

O

Ph

Ln(OTf)3 (1 equiv.)Mn(OAc)3, CF3CH2OH,

- 5 oC+

R = CHMe2

yield: 77%dr: 38 :1

major

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(a) Mn(OAc)3•2H2O(2.2equiv),Yb(OTf)3•H2O (1.0 equiv), CF3CH2OH, -5 oC, 77%; (b) KHMDS, THF, -78oC to -30 oC, then PhNTf2, 95%; (c) DIBAL-H (2.2 equiv), CH2Cl2, -78 to -30 oC, 20 h, 63%; (d) CO, Bu3N, Pd(Ph3P)4, LiCl, CH3CN, 65 oC, 12 h, 93%; (e) BBr3, CH2Cl2, -78 oC to rt, 98%;


OCH3

O

O

O

Ph

H

OCH3

O

O

O

Ph

H

OCH3

O

O

38 : 1 dr by 1H NMR

> 99% ee by HPLC

H

OH

O

O

(a) (b) - (d)

(e)

(+)-triptophenolide

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