Chiral Derivatizing Agents for Absolute Stereochemistry Determination (Moshers Method)

H3C Ph H OH

1-phenylethanol: R or S?

Ph
H3C Ph OH

OCH3 CF3

Ph H3C Ph H O

OCH3 CF3

Cl O

(R )

(R,S R S)

Ph

Ph H3C

OCH3 CF3

Ph Ph H3C H O

OCH3 CF3

OH H

Cl O

(S)

(S,S)

indistinguishable by NMR

(R)-MTPA-Cl

distinguishable by NMR

MTPA Esters as NMR-Distinguishable Chiral Derivatives

Ph R2

OCH3
(S)

Preferred conformation:

R1 H

O O

CF3
electronegative group out of carbonyl LUMO axis

minimizes steric interactions

(Works best for secondary alcohols.)

MTPA Esters as NMR-Distinguishable g Chiral Derivatives

through-space electron withdrawing gg group p deshields R2 (shifts downfield)

Ph O
(S)

R2 R1
face of phenyl group shields R1 (shifts upfield)

OCH3 CF3

(S)-MTPA ester group alters chemical shifts of R1, R2 in a predictable way.

MTPA Esters as NMR-Distinguishable g Chiral Derivatives

Ph R2 R1 H O
(S)

OCH3 CF3 R1

R2

H3CO O
(R )

Ph CF3

(R) )-MTPA MTPA ester group has opposite effect on chemical shift shift. So, if we define = S R, < 0, must be R1. If a nucleus shows > 0, , must be R2.

MTPA Esters as NMR-Distinguishable Chiral Derivatives

H3C Ph H OH

= S R > 0.
-CH3 must be on OCH3 (back)side.

Ph H3C Ph H O

OCH3 CF3

(S ester)

H3C Ph H

H3CO O

Ph CF3

(R ester)

Troy Ryba

MTPA Esters as NMR-Distinguishable Chiral Derivatives

H3C Ph H OH

Ph H3C Ph O

OCH3 CF3

H < 0. 0

(R,S)

Ph Ph H O

OCH3 CF3 H3C Ph H

H3CO O

Ph CF3

CH3 O

(R,R R R)

MTPA Esters as NMR-Distinguishable Chi l Derivatives Chiral D i ti

+0 19 +0.19

= S R
+0.47, +0.40
H H

+0.32
H H H

OCH3 OH

-0.06 H
H

+0.13
Ph OCH3 CF3

-0.06 0 06

-0.03 H -0.05

H H O H H

(S ester)

-0.07 0 07

ottelione A (?)

Hollie Lewis

Other Chiral Derivatives and C Complexing l i Agents A t

(There are lots.)

+
3 3

+
3