Determining the Solution State Orientation of a Ti Enolate via Stable Isotope Labeling, NMR Spectroscopy, and Modeling Studies

Abstract

Our group has used Ti-promoted aldol additions with an oxazolidineselone as the chiral auxiliary with much success. In these reactions, the Se atom in the auxiliary both promotes stereospecific addition as well as reports on, through the use of 77Se NMR spectroscopy, the ratio of diastereomers produced and the geometry of intermediates as the reaction proceeds. Through stable isotope labeling and NMR spectroscopy, we are able to experimentally observe a Ti enolate in solution and gain insight into its structure and reactivity. Results from molecular modeling calculations are also presented for comparison with NMR data.

Use of chiral auxiliaries in the asymmetric synthesis of biologically active compounds: A review

“…Boron enolates, including various oxazolidinone derivatives, were examined crystallographically, spectroscopically, and computationally . However, there is limited experimental evidence to confirm the mechanism of reactions involving simple boron enolates and oxazolidinone‐based compounds …”

Current Progress in the Acetate/Methyl Ketone Aldol Reaction

“…Replacing the carbonyl oxygen with a selenium atom gives an oxazolidineselone (83) with aldehydes [73]. The selenium atom is useful not only to guide the stereochemical outcome of the reaction [74] but also to easily determine crude diastereomeric ratios through 77 Se NMR as well as serve act as a chiral interrogation tool. The selenium atom is useful not only to guide the stereochemical outcome of the reaction [74] but also to easily determine crude diastereomeric ratios through 77 Se NMR as well as serve act as a chiral interrogation tool.…”

“…The selenium atom is useful not only to guide the stereochemical outcome of the reaction [74] but also to easily determine crude diastereomeric ratios through 77 Se NMR as well as serve act as a chiral interrogation tool. Our group has also used the oxazolidineselone auxiliary along with 77 Se enrichment to provide useful details in the orientation of a titanium enolate at -60 o C (87a,b) [74]. Our group has also used the oxazolidineselone auxiliary along with 77 Se enrichment to provide useful details in the orientation of a titanium enolate at -60 o C (87a,b) [74].…”

Evans Enolates: Solution Structures of Lithiated Oxazolidinone-Derived Enolates

“…6,7 Presumably the absence of crystal structures stems from limiting physical properties rather than a lack of interest; we have joined the ranks of those who have failed to grow diffractable crystals. Spectroscopic determination of the structures of enolates in solution is inherently difficult owing to the absence of usable O–M scalar coupling, and we have found only a single spectroscopic study of a boron-based Evans enolate.…”