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NMR spectroscopy provides several tools in the field of the identification and quantification of chiral compounds, based on the use of suitable chiral auxiliaries which have the role of converting enantiomeric mixtures into their diastereoisomeric derivatives or solvates, the NMR resonances of which are distinguishable in principle. In this survey particular attention is focused on the literature regarding the use of NMR spectroscopy for the identification and quantification of chiral drugs and metabolites.

A pathway for the formation of 3-butadienyl-1-tosylpyrroles from 3-acyl derivatives via secondary and tertiary 3-hydroxyalkyl-1-tosylpyrroles has been developed. The dehydration of the alcohols intermediates is the crucial step: conditions for high chemo- and diastereocontrol are described. © 2014 HeteroCorporation.

A theoretical investigation on the regio- and stereoselective outcomes of the hydroformylation reaction with an unmodified rhodium catalyst (H—Rh(CO)3) was carried out at the B3LYP/SBK(d) level on related chiral olefins, namely (1-vinyloxy-ethyl)-benzene (1) and (1-methyl-but-3-enyl)-benzene (2). A thorough and computationally expensive examination of the various possible H—Rh(CO)3-olefin complex intermediates was performed, in order to determine, interpret, and eventually predict, the regio- and stereoselectivity of the aforementioned reactions, whose products are a mixture of the linear aldehyde and of two diastereomers of the branched aldehyde. Regio- and diastereoselectivity of the reaction have been experimentally determined via hydroformylation runs at 20° and 100° C for 1 and at 20° C for 2. The theoretical results obtained are in good agreement with the experimental ones, which put forward a high chiral discrimination for chiral vinyl ether substrates in contrast to the lack of regio- and diastereo-selectivity observed in the hydroformylation of 2. For the hydroformylation of 1, a regioselectivity ratio (B:L) of 72:28 and a diastereoselectivity ratio (b:b’) of 97:3 have been computed which compare well to the corresponding experimental results (85:15 and 88:12). Therefore, theoretical calculations can give reliable estimates of regio- and diastereoselectivity provided a careful and accurate surface scan is performed for the alkyl-rhodium intermediates and the reaction is carried out at room temperature and, hence, in the absence of branched to linear alkyl isomerization.

The rhodium catalyzed hydroformylation of beta-isophorone (1a) should afford, as only oxo-product, the aldehyde 4-formyl-3,5,5- trimethylcyclohexan-1-one (2a), an important intermediate for the preparation of delta-Damascone, a floral woody fragrance used for soaps, shampoos, foam baths, etc. Surprisingly, under the reaction conditions adopted by us, we obtained two isomeric aldehydes, namely the expected 2a, formed in a small amount, and the (3,3-dimethyl-5-oxo-cyclohexyl)acetaldehyde (5a), that resulted to be the preponderant oxo-product. The chemoselectivity of the reaction was strongly affected by the substrate isomerization to beta-isophorone (3a) and by the extensive formation of the corresponding saturated ketone 4a, so lowering the efficiency of the whole process. However, by perfoming the hydroformylation on a beta-isophorone derivative without the possibility of conjugation of the two double bonds, namely the ketal 7,9,9-trimethyl-1,4-dioxa-spiro[4.5]dec-7-ene (1b), the chemoselectivity of the reaction strongly increased and the amount of the hydrogenation product was rather low. In any case the predominant oxo-product was the acetaldehyde derivative 5b, while the aldehyde 2b, deriving from the attack of the formyl group on the less substituted carbon atom of the olefinic double bond, was produced in a very small amount.

The formation of 1-acetyl-6-methyl-8-hydroxy-5,6,7,8-tetrahydroindolizine (3) from 3-methyl-4-(3-acetylpyrrol-1-yl)butanal (2), coming from the rhodium catalyzed hydroformylation of 2-methyl-3-(3-acetylpyrrol-1-yl)prop-1-ene (1), is reported. Evidences for both the complete diastereoselective cyclization of 2 and configuration determination in 3 via 1H, 13C and IR spectra are reported.

6-Methyl-5,6-dihydroindolizine and 3- or 2-ethyl derivatives were obtained via a one-pot hydroformylation/cyclization/dehydration sequence starting from 1-(2-methyl-2-propenyl)pyrroles. 7-Phenyl-5,6-dihydroindolizine and 5-methyl-5,6-dihydroidolizine were similarly synthesized. An easily occurring electrophilic aromatic substitution by the carbon atom of the carbonyl group on the alpha position of the pyrrole ring with the formation of the six-membered ring, is the key step of the process.

A comparison between experimental and theoretical data on regioselectivity concerning the hydroformylation of several vinyl substrates (propene, 2-methylpropene, 1-hexene, 3,3-dimethylbutene, fluoroethene, 3,3,3-trifluoropropene, vinylmethylether, allylmethylether, styrene) with unmodified rhodium catalysts is reported. Various H-Rh(CO)3-olefin complexes are examined at the B3P86/3-21G or /6-31G* level (ECP & LANL2DZ for Rh) and compared to the adducts with modified catalysts, such as H-RhPH3(CO)2. The computed geometries are in satisfactory agreement with the X-ray ones. The activation energies for the alkyl rhodium intermediate formation, computed at either level along the pathways to branched or linear aldehydes, allow one to predict the regioselectivity ratios, since they are in very good agreement with the experimental ones evaluated for the isomeric aldehydes.