Relative and Absolute Stereochemistry of Secondary/Secondary Diols:  Low-Temperature ¹H NMR of Their bis-MPA Esters

Abstract

Comparison of the room- and low-temperature 1H NMR spectra of the bis-(R)- or bis-(S)-MPA ester derivative of an open chain sec,sec-1,2-diol allows the easy determination of its relative stereochemistry and in some cases absolute configuration. If the diol is anti, its absolute configuration can be directly deduced from the signs of DeltadeltaT1T2 for substituents R1/R2, but if the relative stereochemistry of the diol is syn, the assignment of its absolute configuration requires the preparation of two derivatives (both the bis-(R)- and bis-(S)-MPA esters), comparison of their room-temperature 1H NMR spectra, and calculation of the DeltadeltaRS signs for the methines Halpha(R1) and Halpha(R2) and R1/R2 protons. The reliability of these correlations is validated with 17 diols of known absolute configuration used as model compounds.

Asteriscane-Type Sesquiterpenoids from the Soft Coral Sinularia capillosa

“…The absolute configuration of 1 was determined using the modified Mosher's method. 20 First, reduction of 1 by NaBH 4 yielded 1a ( Figure 2). The NOE interaction between H-6 (δ H 3.49,dd,J = 2.5,10.5 Hz) and H [3][4][5][6][7][8][9][10][11][12][13][14][15]d,J = 6.8 Hz) in association with the absence of NOE interaction between H 3 -14 (δ H 1.36, s) and H-6 indicated H-6 of 1a had the same orientation as that of H 3 -15 and was on the opposite face compared to H 3 -14.…”

“…The absolute configuration of 10 was determined by the modified Mosher's method. 20 Analysis of the Δδ RS (δ R − δ S ) values ( Figure 3) resulted in a 10S assignment. Thus, the other stereogenic centers in 10 were assigned as 2R, 3R, 6S, and 7R.…”

Assignment of absolute configuration using chiral reagents and NMR spectroscopy

“…In addition, lowering the temperature of 1,2-diol derivatives with only one MPA enantiomer results in characteristic changes in the Dd T1T2 values that can be used to confirm the configurational assignment. 72 The absolute configuration of 1,2-primary,secondary diols can also be assigned on the basis of bis-9-AMA esters. One strategy is to prepare derivatives with (R)-(2)-and (S)-(1)-9-AMA and use the perturbation of the pro-(R) and pro-(S) positions of the methylene group of the primary diol moiety.…”

“…148 With NTCA, an a-hydroxyamide is formed in the derivatization reaction. The derivative has an eclipsed conformation because of an intramolecular hydrogen bond (72) 151 associate through specific hydrogen bonding interactions with primary amines. Shielding from the aryl ring of these reagents causes predictable changes in the spectrum of the amine that correlate with absolute configuration.…”

Synthesis and determination of the absolute configuration of (−)-(5R,6Z)-dendrolasin-5-acetate from the nudibranch Hypselodoris jacksoni

“…6). The H-6 protons in ( R,R )- 11 and ( R,S )- 11 resonated at δ H 5.04 and at δ H 5.13, respectively, in agreement with H-6 of the ( R,R )-isomer positioned in the shielding cone of the aryl ring of the MPA moiety [25]. The diastereotopic H-4 signals in ( R,S )- 11 at δ H 2.51 and 2.58 were shielded compared to those in ( R,R )- 11 (δ H 2.64, 2.74).…”