Enesulfonamides as Nucleophiles in Catalytic Asymmetric Reactions

Abstract

Enamines and metalated enamines are useful as nucleophiles in synthesis because of the resonance-donating property of the nitrogen atom, which is greater than that of oxygen atoms, thus they are more reactive than the enols and enolates. [1] Asymmetric reactions of enamines and metalated enamines have been reported. Yamada et al. first reported the chiral nonracemic enamines 1 which were derived from ketones and secondary amines [2] and subsequently several chiral enamines such as 2, based on this concept, have been developed and successfully employed. [3] Recently the research group of Ellman reported the first use of metalated enamines 3 derived from chiral N-sulfinylimines in addition reactions to aldehydes.[4] Since in this case primary sulfinamide-derived Nsulfinylimines were employed, the products were b-hydroxy-N-sulfinylketimines which could be reduced stereoselectively to afford either the syn-or anti-1,3-amino alcohols.Although high diastereoselectivity was observed in many of the above cases, stoichiometric amounts of the chiral component (as well as stoichiometric amounts of a strong base to prepare the metalloenamines) were necessary. Recently we reported the development of highly diastereoand enantioselective addition reactions of enecarbamates to ethyl glyoxylate.[5] These reactions proceeded smoothly with high selectivity in the presence of a catalytic amount of a chiral Lewis acid, and was marked by a stereospecific conversion of a-substituted ketone-derived enecarbamates into 1,3-imino alcohols. Despite the importance of enecarbamates, direct methods of synthesizing enecarbamates from the corresponding ketones have not been developed to the same extent as other types of enamines or imines.[6] Herein we report the first asymmetric nucleophilic addition reactions of a wide range of readily prepared enesulfonamides.[7] The enesulfonamides could be rapidly and efficiently synthesized from the corresponding ketones and underwent smooth reactions with a range of electrophiles such as ethyl glyoxylate, azodicarboxylate, and phenylglyoxal in stereoselective fashion. The product sulfonylimines could be readily reduced to the corresponding sulfonamides, which are important functional groups in medicinal chemistry. [8] Enesulfonamides were synthesized from the corresponding ketones via the N-sulfonylimine intermediates (Scheme 1).[9] Separation of the geometric isomers was achieved by column chromatography on silica gel or recrystallization. [10] In contrast to the enecarbamates, which were synthesized from the corresponding nitriles or a,b-unsaturated carboxylic acids, [6] a wide range of enesulfonamides could be synthesized directly from the corresponding ketones and sulfonamides by modification of a previously reported method. [9] The reaction of enesulfonamides with ethyl glyoxylate, which was freshly distilled from a commercially available solution of the polymer in toluene, was performed in the presence of the complex formed between Cu I and diimine ligand 5. Our investigation began with a survey of...

Discovery and Synthesis of Hydronaphthoquinones as Novel Proteasome Inhibitors

“…29 The sulfonamide building blocks that were not commercially available were synthesized according to a reported protocol. 30 The sulfonamide building blocks either commercially available or in-house synthesized were then regioselectively coupled to naphthoquinone intermediates 8a–c according to a procedure that has been widely used in the formation of sulfonimide building blocks 31 using titanium(IV) chloride and triethylamine with conventional heating. We modified the conditions of this reaction (i.e.…”

Synthesis of Some C2‐Symmetric Bidentate Ligands and Their Complexes Derived from Feist's Acid

“…IR Spectra: in KBr; FT-IR-800 spectrophotometer; n in cm À1 . 1 H-, 13 C-, and 31 P-NMR spectra: Geol 400 spectrometer at 400 MHz ( 1 H), 100.6 MHz ( 13 C), and 121.5 MHz ( 31 P); in CDCl 3 or (D 6 )DMSO; d in ppm rel. to Me 4 Si as internal standard, J in Hz; d in ppm (for 31 P-NMR rel.…”

“…H). 13 C-NMR (CDCl 3 ): 22.8 (2 CH 2 P); 27.2 (2 HÀC); 34.5 (C¼CH 2 ); 60.9 (C¼CH 2 ); 129.1 (each 4 C(3), C(4), C(5) of Ph); 132.9 (4 C(2) and 4 C(6) of Ph); 139.2 (4 C(1) of Ph). 31 This crude product was dissolved in anh.…”

“…H-NMR (CDCl 3 ): 1.32 (t, J ¼ 7.4, MeCH 2 O); 2.15 (s, MeÀC(4)); 2.32 (s, MeÀC(6)); 4.28 (q, J ¼ 7.3, MeCH 2 O); 5.94 (s, HÀC(3)) 13. C-NMR (CDCl 3 ): 14.2 (MeCH 2 O); 19.6 (MeÀC(6)); 21.2 (MeÀC(4)); 61.7 (MeCH 2 O); 111.9 (C(5)); 113.2 (C(3)); 154.4 (C(4)); 160.7 (C(2)); 164.6, 165.5 (COOEt, C(6)).…”

Copper‐Catalyzed Chloroamination of Alkynes: Highly Regio‐ and Stereoselective Synthesis of (E)‐β‐Chloro‐Enesulfonamides

“…However, the application of heteroatom-halogen bonds in the addition reactions of alkynes is very limited, [6] and the addition reactions to alkynes with nitrogen-halogen bonds still remains a challenge. [8] In general, enesulfonamides are synthesized from the corresponding ketones via the N-sulfonyl-A C H T U N G T R E N N U N G imine intermediates. [8] In general, enesulfonamides are synthesized from the corresponding ketones via the N-sulfonyl-A C H T U N G T R E N N U N G imine intermediates.…”