Synthesis of Chiral Cyclic Nitrones by Asymmetric Addition of β‐Ketosulfones to Nitroalkenes followed by Reductive Cyclization

Abstract

The first organocatalytic addition of β-ketosulfones to nitroalkenes catalyzed by thiourea cinchona alkaloids is presented. The readily obtained addition products were selectively transformed into chiral nitrones by reduction of the nitro group and in situ cyclization (up to 99:1 e.r. and >98:2 d.r.). Moreover, the utility of this method has additionally been demonstrated by the further transformation to functionalized N-hydroxypyrrolidines that possess a quaternary center by addition of trimethylsilyl cyanide (TMSCN) to the C=N bond of the cyclic nitrones in the presence of a Lewis acid.

Advances in Synthesis of Enantioenriched Chiral Sulfones by Enantioselective Conjugate Addition Reactions

“…A novel catalyst system which consisted of chiral thiourea and N-heterocyclic carbene was used by Chi et al to synthesize enantiomeric β-sulfonyl ketones 130 through the enantioselective sulfonation of enones 125 with sulfonyl imines 124 in 2013 (Scheme 35). [54] The authors proposed a catalytic cycle in which the N-Heterocyclic carbene catalyzed the NÀ S bond cleavage of sulfonyl imide and produced a nucleophilic sulfur anion. Subsequently, sulfurous anion interacted with thiourea catalyst through the N-H hydrogen bond, and then attacked the unsaturated ketones which was activated by tertiary amines in an enantioselective manner.…”

Tunable Zinc-Mediated Reductive Cyclization of Diastereomeric 3-Nitro-4-phenacyl-2-(trihalomethyl)chromanes to Fused Pyrroline N-Oxides, Pyrrolines, and Pyrrolidines

“…One of the simplest and most efficient methods for the synthesis of 1-pyrroline N -oxides, 1-pyrrolines, and pyrrolidines is the reductive cyclization of γ-nitroketones, − mostly due to their availability. The process is usually carried out either under catalytic hydrogenation conditions or under the action of transition metals such as Zn or Fe.…”

“…When zinc is used as a reducing agent, it is possible to obtain all of the above 5-membered azaheterocycles from γ-nitroketones depending on the conditions. For the synthesis of nitrones and pyrrolines, the reductive systems such as Zn/AcOH and Zn/NH 4 Cl are often used. In order to avoid the formation of pyrrolidines, the reaction is usually carried out at temperatures not exceeding room temperature.…”

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

“…Thus, ketonitrosulfones were obtained with good enantiomeric excesses via asymmetric addition of α-nitrosulfones to enones in the presence of organocatalysts [41]. Asymmetric addition of β-ketosulfones to nitroalkenes was implemented using various organocatalysts [42]. The reaction of ketosulfones with nitroalkenes in the presence of organocatalysts shows high enantioselectivity, however, leads to a mixture of diastereomers.…”