Catalytic Asymmetric Synthesis of β‐Sultams as Precursors for Taurine Derivatives

Abstract

Beta-sultams, biologically interesting sulfonyl analogues of beta-lactams, have been prepared by an organocatalytic asymmetric formal [2+2]-cycloaddition approach of non-nucleophilic imines with alkyl sulfonyl chlorides. In the case of very electron poor N-tosyl imines derived from chloral or ethylglyoxylate, this reaction type was catalyzed by cinchona alkaloids providing the heterocycles in high yield, with good diastereoselectivity and up to 94% ee. Mechanistic investigations suggested that the product formation proceeded via a zwitterionic imine-catalyst adduct. The scope was significantly extended by 2-pyridylsulfonyl imines derived from non-activated aromatic aldehydes employing Yb(OTf)3 as Lewis acid cocatalyst. The synthetic value of the strained enantioenriched beta-sultams was demonstrated by smooth nucleophilic ring opening reactions with O-, N- and C-nucleophiles yielding a variety of acyclic beta-aminosulfonyl (taurine) derivatives (sulfonates, sulfonamides, sulfones) without racemization or epimerization.

Lewis Acid/Base Catalyzed [2+2]‐Cycloaddition of Sulfenes and Aldehydes: A Versatile Entry to Chiral Sulfonyl and Sulfinyl Derivatives

“…Whereas in the case of 7, both enolate C atoms are sp 2 -hybridized, the S atom in 5 and presumably also the a-C atom are pyramidalized, in analogy to the majority of sulfone carbanions bearing one alkyl group at the a-C atom as the only substituent. [20][21][22] This implies that diastereomeric zwitterionic species (5 A and 5 A') are formed, whereas in the ketene case the cinchona alkaloid is supposed to bind selectively trans to the residue R in 7 to minimize unfavorable steric interactions. [2] The absolute configuration of the b-sultone products 2 primarily depends on the reactive configuration of the zwitterion at the a-position.…”

Bispalladacycle‐Catalyzed Michael Addition of In Situ Formed Azlactones to Enones

“…Silver carboxylates or nitrate performed in general inferior in terms of the enantioselectivity (Table 3, entries 6-9), whereas with the non-coordinating BF 4 À ion a good enantioselectivity was attained ( Table 3, entry 10) at the expense of a low reactivity. A major improvement of the product yield was achieved in case of silver sulfonates or acetate by addition of catalytic or stoichiometric amounts of NaOAc (Table 3, entries [11][12][13][14][15][16]. To further accelerate the conjugate addition the model reaction was conducted at 30 8C by using 2 mol % of the precatalyst and two equivalents of enone 2 A.…”

“…[9,10] Afterwards, organocatalytic protocols have been described for other highly reactive Michael acceptors. [11][12][13][14][15] Being part of our program to study cooperative effects in asymmetric catalysis, [16] we report herein the first catalytic asymmetric conjugate additions of azlactones to enones [17][18][19] and describe the first catalytic asymmetric examples in which the azlactone substrates are formed in situ, starting either from racemic N-benzoyl a-amino acids or even from unprotected racemic amino acids.…”

Organocatalyzed Cycloadditions

“…quinine, catalyzed formal [2 + 2] cycloadditions of sulfonylchlorides 177 and highly reactive non-nucleophilic imines178, affording the b-sultams 180, Scheme 3.56 [72]. Hua and his co-workers reported a highly efficient cycloaddition of vinylarenes 181 with electron-deficient alkynes 182, affording 1,2-disubstituted-3,4-dihydronaphthalenes 183, in the presence of DMF•DMA (N,N-dimethylformamide dimethyl acetal) as organocatalyst, Scheme 3.57 [73].…”