2-Cyano-2-indolylpropanoic acid as a chiral derivatizing agent for the absolute configuration assignment of secondary alcohols and primary amines by 1 H NMR and VCD

Vibrational Circular Dichroism Absolute Configuration of Natural Products From 2015 to 2019

“…Levorotatory flustramine B, occurring in the bryozoa Flustra foliacea (L.), was synthesized and its AC was determined by VCD and VCDEC as (3a S ,8a R )-( 273 ) (Figure 78) through the AC of oxazolidinone and amide intermediates. 130 Similar studies of indolyl derivatives were developed for the AC assignment of secondary alcohols in the ester series 131 and primary amines in the amide series. 132…”

“…Exceptions to such calculations are those limited cases for which VCDEC was employed. 33,40,73,74,88,91,112,130 -132 A relevant aspect of the calculation task is the selection of the level of theory that has to be used to provide a good spectra comparison and consequently a confident AC assignment, which implies balancing spectra similarity and invested computer resources for the calculations. This situation is not very relevant when a single stereogenic center is present in the molecule under study since the AC is correctly defined in most cases, although with different levels of confidence.…”

“…128 Reactions of glutaraldehyde with the 4 stereoisomers of commercial sphingosine generated the respective tricyclic products 269-272 ( Figure 77 129 Levorotatory flustramine B, occurring in the bryozoa Flustra foliacea (L.), was synthesized and its AC was determined by VCD and VCDEC as (3aS,8aR)-(273) (Figure 78) through the AC of oxazolidinone and amide intermediates. 130 Similar studies of indolyl derivatives were developed for the AC assignment of secondary alcohols in the ester series 131 and primary amines in the amide series. 132 The AC of a levorotatory alkaloid, found in Galanthus woronowii and G. nivalis, was established using several solution-state techniques like NMR, VCD, and ROA as (−)-(4aS, 6R,8aS)-galantamine (274) (Figure 78).…”

The Assignment of the Absolute Configuration of β-Chiral Primary Alcohols with Axially Chiral Trifluoromethylbenzimidazolylbenzoic Acid

“…Purified by CC (gradient hexane/ EtOAc 1:2 → EtOAc), 12 mg (40%) yield, a light yellow oil: 1 H NMR (500 MHz, CDCl 3 ) δ 8.13 (dd, J = 7.8, 1.7 Hz, 1H), 7.96 (dt, J = 8.2, 0.9 Hz, 1H), 7.76 (td, J = 7.7, 1.6 Hz, 1H), 7.68 (td, J = 7.7, 1.3 Hz, 1H), 7.46 (dd, J = 7.9, 1.0 Hz, 1H), 7.41 (ddd, J = 8.2, 7.2, 1.2 Hz, 1H), 7.36−7.33 (m, 1H), 7.31−7.24 (m, 3H), 7.06 (dd, J = 7.6, 1.9 Hz, 2H), 6.95 (dt, J = 8.2, 0.9 Hz, 1H), 4.82 (t, J = 5.5 Hz, 1H), 4.48 (dd, J = 11.1, 8. 6.96 (dt, J = 8.2, 0.9 Hz, 1H), 4.09 (dd, J = 10.9, 6.5 Hz, 1H), 3.99 (dd, J = 10.9, 7.9 Hz, 1H), 3.90 (s, 3H), 2.73−2.61 (m, 1H), 1.08 (d, J = 7.0 Hz, 3H); 13…”

“…The most common NMR technique involves the transformation of the analyte into two diastereomers using a suitable chiral derivatizing agent (CDA). − The NMR spectra of these two diastereomers are measured and compared. The difference in the chemical shifts (Δδ RS ) of given signals and the knowledge of preferred conformations allow for the assignment of the given substituents in space to determine the absolute configuration …”