Current Literature Jingbo Xiao June 5th, 2004

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Stereospecific and Stereodivergent Construction ofQuaternary Carbon Centers through Switchable

Directed/Nondirected Allylic Substitution

Bernhard Breit*, Peter Demel, Christopher Studte

Institut für Organische Chemie und Biochemie Albert-Ludwigs-UniversitätFreiburg, Germany

Angewandte Chemie International Edition,2004 Early View Communication

Current Literature Jingbo Xiao June 5th, 2004

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Quaternary Carbon Centers1. Ionic constructions which may involve the participation of the tertiary carbon atom as a

nucleophilic or as an electrophilic reaction partner

NH

NO

NH

NO1. LDA (2 eq.)

2. BrCH2CO2Me

CO2Me Cl (n-BuC )3Al+

71% n-Bu

2. Oxidative and reductive coupling reactions

HO

OH

VOCl375%

HO

O

3. Rearrangement reactions

R1 OHR2X R4

R3-X- R1 O

R2R3 R4 O

O

2300CO

O

4. Cycloaddition reactionsTetrahedron, 1980, 36, 419

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Asymmetric Creation of Quaternary Carbon Centers

1. Enantioselective Creation (one chiral center was generated in product)

A. Enantiodifferentiating Reactions (0 to 1)1. Chemical Methods2. Biological Methods

B. Diastereodifferentiating Reactions (2 to 1)1. Use of Chiral Nucleofuges2. Intramolecular Chiral transfer Reactions3. Miscellaneous Reactions

2. Diastereoselective Creation (two chiral centers were generated in product)

A. Enantiodifferentiating Reactions (0 to 2)

B. Diastereodifferentiating Reactions (1 to 2)1. Alkylation of Chiral Enamines2. Alkylation of Chiral Enolates and relater Carbanions3. D-A Cycloadditions4. Micellaneous Reactions

Chem. Rev., 1993, 93, 2037

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Intramolecular 1, 3-Chiral transfer Reactions

[2, 3]-Sigmatropic Rearrangement

O R2G

R1 [2,3]-wittig R1 R2

HO G

1 3

Chem. Rev., 1986, 86, 885[3, 3]-Sigmatropic Rearrangement

TBDMSO OBnOH

triethyl orthoacetatepropion acid, 135 oC

TBDMSO OBn1

OEtO

3

Carb. Res., 2000, 328, 37SN2’ Reaction

Ii-Bu

1. t-BuLi2. ZnBr23. CuCN.2LiCl

4.Me

Bu

OCOC6F5

i-Bu

Bu1

3

Org. Lett., 2003, 5, 2111

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SN2’ Intramolecular 1, 3-Chiral transfer Reactions

Advantage:

1. Allows the introduction of variable nucleophiles, such as alkyl, alkenyl and aryl groupsinto an existing carbon skeleton.

2. The reactions generally proceed by anti attack of the nucleophile with respect to theleaving group.

Disadvantage:

1. Simultaneous control of the chemo-, regio- and stereo-chemistry is normally difficult.

2. The stereochemistry of the product was determined by the stereochemistry of the startingmaterial.

3. Usually, excess of organometallic reagent is required to push the reaction to complete.

Current Literature Jingbo Xiao June 5th, 2004

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Reagent-directing leaving groups -syn attack

Carbamates as the leaving groups

OCONHPhD

LiCuMe2

D

J. Org. Chem., 1983, 48, 715

Benzothiazole as the leaving group

R1 R2

S S

NLiCuR2

R1 R2

R

J. Org. Chem., 1990, 55, 2295

o-DPPB as the leaving group (DPPB = diphenylphosphanylbenzoate)

O(o-DPPB) 1. eq. CuBr.SMe21.1 eq. MeMgIEt2O, rt, 2h

PPh2

O ODPPB

Adv. Synth. Catal., 2001, 343, 5

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Switchable Directed/Nondirected Leaving Group

ACEI, 2004, Early View Communication

Current Literature Jingbo Xiao June 5th, 2004

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o-DPPB-directed Allylic Substitution

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Directed/Nondirected Allylic Substitution

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Application of Switchable Directed/Nondirected Substitution in Six-membered-ring System

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Conclusion

1. The o-DPPB/o-DPPB oxide system can be used as a switchabledirecting/nondirecting leaving group in a copper-mediated allylicsubstitution reactions.

2. Both enantiomers of the substitution product are readily availablefrom one enantiomer of the substrate.

3. The chemo-, regio- and stereoselectivity are quite good.

4. Large excess of organometallic reagents is NOT necessary.

5. The switchable leaving groups are reusable.