Efficient Synthesis of Cyclic Sulfoximines from N‐Propargylsulfinamides through Sulfur–Carbon Bond Formation

Abstract

Cyclic sulfoximines were readily synthesized by the cyclization of N‐propargylsulfinamides without using expensive and toxic metal catalysts. This cyclization proceeded without loss of optical purity of chiral sulfinamides through the unusual sulfur–carbon bond formation promoted by an inexpensive inorganic base. This stereospecific cyclization offers a general approach to the asymmetric synthesis of chiral cyclic sulfoximines as an emerging heterocycle in medicinal chemistry.

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] .…”

“…In 2014, we reported an unprecedented one‐step method for the synthesis of enantiomerically pure benzo fused cyclic sulfoximines through stereoselective [3+2] cycloaddition between N ‐ tert ‐butanesulfinyl imines and in‐situ generated arynes by using (phenylsulfonyl)difluoromethyl group (PhSO 2 CF 2 ) as a facilitating group ( Scheme 1 ,a ), [21] which not only represents the first efficient method for the construction of sulfoximine moiety through direct sulfur−carbon bond formation between a sulfur‐nucleophile and a carbon electrophile, [19–24] but also stands for an efficient protocol providing access to the optically active cyclic sulfoximines [21–24] . Moreover, the so‐obtained PhSO 2 CF 2 ‐substituted cyclic sulfoximines can be easily transformed into the HCF 2 ‐substituted cyclic sulfoximines through reductive desulfonylation or into the cyclic sulfinamides through stereoselective de‐ tert ‐butylation and formal nucleophilic substitution of the PhSO 2 CF 2 group [21] .…”

Increasing Complexity: A Practical Synthetic Approach to Three‐Dimensional, Cyclic Sulfoximines and First Insights into Their in Vitro Properties

“…Recently, Bolm and co‐workers reported an approach, with broad functional‐group tolerance, to five‐ and six‐membered cyclic sulfoximines 3 by intramolecular imidation of azido‐containing sulfoxides with a commercially available iron(II) phthalocyanine as catalyst . Moreover, Maruoka and co‐workers have outlined a procedure for the synthesis of unsaturated five‐membered cyclic sulfoximines from N ‐propargylsulfinamides through sulfur–carbon bond formation …”

“…[11] Moreover,M aruoka andc o-workersh ave outlined ap rocedure for the synthesis of unsaturated five-membered cyclic sulfoximinesf rom N-propargylsulfinamides through sulfur-carbon bond formation. [12] The development of significantly improved methodologies for the synthesis of sulfoximines 2 has been an important trigger for the increased interesti nt his functional group by the drug-discovery community in recenty ears. [2d] Ar ecent example is ao ne-pot procedure that allows the direct conversion of thioethers to NH-sulfoximines 2 (R 3 = H), first reportedb yB ull, Luisi, andc o-workers.…”

Synthesis of Isothiazoles through N-Propargylsulfinylamide: TFA-Promoted Sulfinyl Group-Involved Intramolecular Cyclization

“…Since tert -butanesulfinamide was first discovered by the Ellman group in 1997 for easy access to chiral amines, this reagent has received much research attention from the chemical community because it is stable, readily available, and usually brings high diastereoselectivity in the asymmetric synthesis (Scheme a). − In addition to excellent chiral induction ability, this chiral tert -butanesulfinyl group can be easily and conveniently removed with the use of trifluoroacetic acid (TFA) or HCl/methanol (Scheme b). In the past two decades, a set of reagents based on the N - tert -butanesulfinyl scaffold fused to nitrogen-containing heterocycles were developed for simplifying stereocontrolled access to organic compounds .…”