Resolution and assignment of the absolute stereochemistry of a trans-2,3-diarylpyrrolidine LTB4 inhibitor intermediate

2-Azaallyl Anions, 2-Azaallyl Cations, 2-Azaallyl Radicals, and Azomethine Ylides

“…Surprisingly, there are very few examples beyond the initial reports in which these cycloaddition reactions with semistabilized 2-azaallyl anions play a key role in the construction of more complex compounds, such as natural products, or items of commercial interest, such as drug candidates. 68 This is in stark contrast to cycloaddition reactions involving nonstabilized 2-azaallyl anions (section 2.3) and azomethine ylides (section 5). Unlike cycloaddition reactions involving heteroatom-substituted nonstabilized 2-azaallyl anions and N-metalated azomethine ylides, there are currently no enantioselective variants of cycloadditions involving semistabilized 2-azaallyl anions, which may account for the greater popularity of the former method for the construction of value-added cyclic amines.…”

“…7500–8000, and therefore contained 35–40 monomers. In 1997, researchers at Boehringer Ingelheim disclosed the use of a [3 + 2] cycloaddition between a semistabilized 2-azaallyl anion and 4-vinylanisole as a means to construct a key intermediate in the synthesis of a trans -2,3-diarylpyrrolidine LTB 4 inhibitor …”

“…As demonstrated above, semistabilized 2-azaallyl anions can react with a large variety of dipolarophiles via [3 + 2] cycloaddition reactions to afford an equally diverse collection of polysubstituted N-heterocyclic compounds. Surprisingly, there are very few examples beyond the initial reports in which these cycloaddition reactions with semistabilized 2-azaallyl anions play a key role in the construction of more complex compounds, such as natural products, or items of commercial interest, such as drug candidates . This is in stark contrast to cycloaddition reactions involving nonstabilized 2-azaallyl anions (section ) and azomethine ylides (section ).…”

“…In 1997, researchers at Boehringer Ingelheim disclosed the use of a [3 + 2] cycloaddition between a semistabilized 2-azaallyl anion and 4-vinylanisole as a means to construct a key intermediate in the synthesis of a trans-2,3-diarylpyrrolidine LTB 4 inhibitor. 68 Conjugated dienes also react with semistabilized 2-azaallyl anions via cycloaddition. For instance, the reaction of isoprene (29) with 6a gave a mixture of two constitutional isomers 30 and 31 (Scheme 10A).…”

Practical Synthesis of an Enantiomerically Pure trans-4,5-Disubstituted 2-Pyrrolidinone via Enzymatic Resolution. Preparation of the LTB4 Inhibitor BIRZ-227

“…Following reaction with a substituted chlorobenzoxazole 2 , milligram quantities were then purified using chiral HPLC to furnish material for initial biological assay. Multigram quantities of (+)- 1 were prepared through scaling up the 1,3-dipolar cycloaddition chemistry and a method of resolving racemic 3 using (−)-diacetone-2-keto- l -gulonic acid 1 …”