MTPA vs MPA in the Determination of the Absolute Configuration of Chiral Alcohols by ¹H NMR

Abstract

Molecular mechanics, semiempirical (AM1), and aromatic shielding effect calculations and DNMR experiments show that MTPA esters are constituted by three main conformers in close populations due to restricted rotation around the Cα−CO and Cα−Ph bonds. The small predominance of one conformer and the simultaneous operation of aromatic shielding and deshielding effects on the alcohol part, due to the orientation of the Ph ring, explains the small Δδ RS values observed. A graphical description of the aromatic magnetic field distribution in the conformers of MTPA and MPA esters and its use to correlate the average chemical shifts with the absolute stereochemistry is presented. Comparison of MTPA with MPA (two conformers) as reagents for determination by NMR of absolute stereochemistry indicates that MTPA esters are intrinsically limited by the greater complexity of their conformational composition, yield very small Δδ RS values, and are consequently less reliable for configurations assignment of chiral alcohols than MPA or other arylmethoxyacetic acid reagents such as (R)- and (S)-α-methoxy-α-(9-anthryl)acetic acids.

Utilização de RMN de ¹H na determinação da configuração absoluta de álcoois

“…É um dos reagentes auxiliares mais populares para reconhecimento da estereoquímica absoluta de álcoois secundários e aminas primári-as, ambos α-substituídos 7,9 . Os ésteres de MTPA, de acordo com cálculos semiempíricos, são constituídos de três confôrmeros principais 10,11 de baixa energia em equilíbrio e com populações similares dos confôrmeros sp 1 , sp 2 e ap 1 independentemente da estrutura do álcool que são gerados pelas rotações em torno das ligações Cα-C=O e Cα-Ph.…”

Siamenols A-D, Four New Coumarins from Mammea siamensis

“…Signals at d H 3.80 (1H, hept, Jϭ6. 7 Hz, H-2ٞ), 1.14 (3H, d, Jϭ6. 7 Hz, H-3ٞ) and 1.20 (3H, d, Jϭ6.…”

“…7 Hz, H-2ٞ), 1.14 (3H, d, Jϭ6. 7 Hz, H-3ٞ) and 1.20 (3H, d, Jϭ6. 7 Hz, H-4ٞ) was assignable to be an isopropyl group.…”

“…7 Hz, H-3ٞ) and 1.20 (3H, d, Jϭ6. 7 Hz, H-4ٞ) was assignable to be an isopropyl group. The remaining signals of two methyl groups on a carbinol carbon side chain at d H 1.25 (H-2Љ) and 1.51 (H-3Љ) and the ABX-type aliphatic protons at d H 3.13 (1H, dd, Jϭ15.4, 9.9 Hz, H-3a), 3.27 (1H, dd, Jϭ15.…”

“…7) Due to the small quantities of all isolated siamenols A-D (1-4), only siamenol C (3) was studied for its absolute stereochemistry by converting it to the corresponding methoxyphenylacetate ester. Siamenol C (3) was esterified with (R)-(Ϫ)-and (S)-(ϩ)-a-methoxyphenylacetic acid (MPA), DCC and DMAP in CH 2 Cl 2 to give 1Ј-O-ester of (R)-(Ϫ)-MPA ester 3a and 1Ј-O-ester of (S)-(ϩ)-MPA ester 3b.…”