Tandem chain extension–Mannich reaction: an approach to β-proline derivatives

Abstract

A zinc carbenoid-initiated chain extension reaction provides access to an organometallic intermediate, which can be used to capture activated imines. Deprotection of the nitrogen and reduction provides access to racemic derivatives of β-proline. The relative stereochemistry of the β-proline can be controlled through use of different activating groups on the imine nitrogen.

Recent Developments in the Stereoselective Synthesis of Nitrogen‐Containing Heterocycles using N‐Acylimines as Reactive Substrates

“…The reactivity of N ‐acylimines toward Reformatsky reagents is known, and efficiently leads to β‐amino acid derivatives . Organozinc reagent 63 obtained by reaction of keto ester 62 with ethyl(iodomethyl)zinc (Furukawa reagent), reacts with N ‐acylimines leading to the corresponding adducts 64 in satisfactory yield and moderate diastereoselectivity (Scheme ) …”

Synthetic Approach toward Enantiopure Cyclic Sulfinamides

“…Surprisingly, the respective fairly standard conditions delivered sulfoximine 12 as the major product rather than the expected cyclopropane. The single comparable example of such atypical reactivity was reported by Zercher et al and regarded primarily as an undesirable synthetic obstacle . Meanwhile, intrigued by the chemo- and stereospecificity observed in the formation of 12 we plan to explore this valuable transformation in greater detail.…”

“…The single comparable example of such atypical reactivity was reported by Zercher et al and regarded primarily as an undesirable synthetic obstacle. 24 Meanwhile, intrigued by the chemo- and stereospecificity observed in the formation of 12 we plan to explore this valuable transformation in greater detail. Further modifications of 3g included diimide reduction 25 to 13 , which in turn was smoothly converted to the tertiary sulfinamide 14 .…”

Synthesis of Enantiopure Benzo Fused Cyclic Sulfoximines Through Stereoselective [3+2] Cycloaddition between N‐tert‐Butanesulfinyl [(2‐Pyridyl)sulfonyl]‐difluoromethyl Ketimines and Arynes

“…The sulfur−carbon bond formation is also viable, [1,14] which mainly relies on the oxidation of sulfinamides to sulfonimidoyl halides or sulfonimidates followed by substitution with carbon nucleophiles [15,16] . However, little attention has been paid on direct S ‐functionalization of sulfinamides or sulfinimines with carbon electrophiles [17–24] . Moreover, cyclic sulfoximines, as a special class of heterocyclic compounds, have attracted attention from chemists due to their potential application as three‐dimensional bioisosteres of relatively flat heterocycles [25–28] .…”