Scribd
Upload
16 views18 pages

GSK Classes 10-12

Uploaded by

kishor
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
16 views18 pages

GSK Classes 10-12

Uploaded by

kishor
Copyright
© © All Rights Reserved
We take content rights seriously. If you suspect this is your content, claim it here.
Available Formats
Download as PDF, TXT or read online on Scribd
You are on page 1/ 18

Asymmetric Allylic Substitution Reactions

• In 1973, Trost and Fullerton reported a new palladium-mediated synthetic reaction termed
allylic alkylation (Trost, B. M.; Fullerton, T. J. J. Am. Chem. Soc. 1973, 95, 292)

• Within a few months, this group reported a stoichiometric asymmetric variant employing
chelating chiral bisphosphine ligands (Trost, B. M.; Dietsche, T. J. J. Am. Chem. Soc. 1973, 95,
8200)

• Four years later, their catalytic version of this reaction set off a storm of work that continues
to this day (Trost, B. M.; Strege, P. E. J. Am. Chem. Soc. 1977, 99, 1649)

• Asymmetric Allylic Alkylation (AAA), generally >90% ee


Tsuji–Trost reaction
or
Trost allylic alkylation
or
Allylic alkylation

Review: Trost, B. M.; VanVranken D. L., Chem. Rev. 1996, 96, 395
Book: Trost, B. M.; Lee, C. In Catalytic Asymmetric Synthesis; Oijima, I., Ed.; Wiley-VCH:
Weinheim, Germany, 2000; Chapter 8E.
1962: Smidt’s palladium-catalysed oxidation of alkenes to carbonyl groups
Angewandte Chemie, 1962,74, 93
Asymmetric Allylic Substitution

Phosphinooxazoline (PHOX) ligands


η2 π-allyl-Pd(0) Π complex

η2 π-allyl-Pd(0) Π complex

η3 π-allyl-Pd(II) complex

Trost, B. M.; Lee, C. In Catalytic Asymmetric Synthesis; Oijima, I., Ed.; Wiley-VCH: Weinheim,
Germany, 2000; Chapter 8E.
Asymmetric Allylic Substitution
inversion inversion

retension

Nature of the nucleophines decide the stereoselectivity of the product

Soft nucleophiles invert the stereochemistry of the π-allyl complex (a net retention of stereochemistry)
Hard nucleophiles retain the stereochemistry of the π-allyl complex (a net inversion of stereochemistry)

Soft nucleophiles: conjugate acids with pKa is less than 25


Hard nucleophiles: conjugate acids with pKa is more than 25

Trost, B. M.; Lee, C. In Catalytic Asymmetric Synthesis; Oijima, I., Ed.; Wiley-VCH: Weinheim,
Germany, 2000; Chapter 8E.
Asymmetric Allylic Substitution
Application

Trost, B. M.; Lee, C. In Catalytic Asymmetric Synthesis; Oijima, I., Ed.; Wiley-VCH: Weinheim,
Germany, 2000; Chapter 8E.
Catalytic Asymmetric C-C bond formation
Asymmetric Cycloaddition Reactions
(Diels-Alder Reaction)

Asymmetric Aldol Reactions

Asymmetric Michael Additions

Asymmetric Cross-Coupling reactions

Asymmetric Nazarov Cyclization

Asymmetric Pd-Catalyzed Cyclization

Asymmetric Kharasch Reaction


(C-O bond formation)
Asymmetric Catalytic Diels-Alder Reaction

Acyloxyborane
from sulfonamide

CH2Cl2

H. Yamamoto, Synlett, 1990, 194


Asymmetric Catalytic Diels-Alder Reaction

Oh et al. Tetrahedron Lett. 1995, 36, 221


Intramolecular Diels-Alder Reaction

Type I: Tether is attached at 4- position of diene

Fused products usually


have 3 or 4 atom tethers

Bridged products rarely observed


(tether must be >9 atoms)

Type II: Tether is attached at 3- position of diene

A combination of steric and electronic factors determine IMDA stereochemistry


Intramolecular Diels-Alder Reaction

Brønsted acid-assisted
chiral Lewis acid (BLA)

With E- diene, anti TS is sterically favored.


Syn TS experiences nonbonding
Yamamoto, H. J. Am. Chem. Soc. 1996, 118 , 3049 interactions between C4-C7.
Enantioselective Aldol Reactions

Catalytic Enantioselective Mukaiyama-Aldol Additions of Enolsilanes


to (Benzyloxy)acetaldehyde
C2-Symmetric Copper(II) Complexes as Chiral Lewis Acids

bis(oxazoline) ligands (BOX ligands); PyBOX; diPh-PyBox


1984: Brunner (BOX ligands); 1989 (Pfaltz; semicorrin);
Nishiyama (1989; PyBOX)
1990: BOX ligands used by Masamune
1994: Prof. V.K. Singh (diPh-PyBox; 1994)

D.A. Evans, et al, J. Am. Chem. Soc., 1999, 121, 669


The trigonal bipyramidal complex square pyramidal copper geometry
was considered unlikely

square pyramidal copper geometry

D.A. Evans et al, J. Am. Chem. Soc., 1999, 121, 669


Enantioselective Michael Addition

D. A. Evans et al, J. Am. Chem. Soc., 2001, 123, 4480


Asymmetric Cross-Coupling reactions
Asymmetric synthesis of 1,1'-binaphthyls via asymmetric cross-coupling

nickel bromide and


(5)-l-[(R)-2-(diphenylphosphino)ferrocenyl]ethyl methyl ether
up to 95% ee
Tamio Hayashi et al. J. Am. Chem. Soc. 1988, 110, 8153

Asymmetric Grignard cross-coupling reaction

(R)-N,N-Dimethyl-1-[(S)-2-
(diphenylphosphino)ferrocenyl]ethylamine

66% ee (34% overall yield in five steps)


(R)-a-curcumene
Kumada et al. Tetrahedron Lett., 1979, 23, 2155
Catalytic Asymmetric Nazarov Reactions

Up to 88% ee

Stereochemical model for the interaction of py-box


complexes with divinyl keto-esters

Varinder K. Aggarwal et al. Org. Lett. 2003, 5, 5075

You might also like