α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• levels of chiral induction, paving the way to enantioenriched β2-amino acids and β2,2-amino acids. Keywords: β-amino acids; tandem reactions; radical–polar crossover; tert-butanesulfinamide; zinc radical transfer; Introduction Dialkylzinc reagents react in aerobic medium with a range of α,β-unsaturated

• -butanesulfinamide (4) and the requisite α-(bromomethyl)acrylates gave satisfactory yields as well. Finally, N-benzyl-N-(tert-butanesulfinyl) α-(aminomethyl)acrylate 10 was prepared by allylation of lithiated N-benzyl tert-butanesulfinamide 9 (Scheme 3). 1,4-Addition reactions Having the requisite α-(aminomethyl

• was poorly efficient with tosylamine, leading to product 7 in low 20% yield [25]. With the aim to develop asymmetric variants, we also considered the synthesis of N-(tert-butanesulfinyl) α-(aminomethyl)acrylates 8a–c. For this purpose, the application of the same protocol with (±)-tert

N-Sulfinylpyrrolidine-containing ureas and thioureas as bifunctional organocatalysts

• Viera Poláčková,
• Dominika Krištofíková,
• Boglárka Némethová,
• Renata Górová,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2021, 17, 2629–2641, doi:10.3762/bjoc.17.176

• with bis(trichloromethyl)carbonate (BTC) afforded the crude product 3b, which was sufficiently pure for use in the next reaction step without further purification (Scheme 1). The next steps of the catalyst synthesis were the attachment of tert-butanesulfinamide 4 to iso(thio)cyanates 3a and 3b with

• pre-catalysts (S,R)-5a and (S,S)-5a A stirred solution of (R)-tert-butanesulfinamide or (S)-tert-butanesulfinamide (0.09 g, 0.75 mmol) in THF (5 mL) was cooled to 0 °C under argon atmosphere. Butyllithium in hexane (0.35 g, 0.82 mmol) was added dropwise, and the solution was stirred for 15 min. The

• , 2973, 1653, 1159, 1237, 1058 cm−1; HRMS (m/z): [M + Na]+ calcd for C15H29N3O3S2, 386.1543; found, 386.1543; [M + H]+ calcd, 364.1729; found, 364.1722. General procedure for the preparation of N-sulfinylurea pre-catalysts (S,R)-5b and ((S,S)-5b) A stirred solution of (R)-tert-butanesulfinamide or (S

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• imines derived from tert-butanesulfinamide. These imines are versatile chiral auxiliaries and have been extensively used as eletrophiles in a wide range of reactions. The electron-withdrawing sulfinyl group facilitates the nucleophilic addition of organometallic compounds to the iminic carbon with high

• -containing heterocycles; N-tert-butanesulfinyl imines; Intoduction Chiral imines derived from tert-butanesulfinamide have been extensively used as electrophiles in a wide range of reactions. The presence of the chiral electron-withdrawing sulfinyl group facilitates the nucleophilic addition of

• organometallic compounds to the iminic carbon [1][2][3]. The ready availability of both enantiomers of tert-butanesulfinamide in large-scale processes, the easy deprotection of the amine under mild acidic conditions, and a practical procedure for recycling the chiral auxiliary [4][5] have contributed to the

A novel and practical asymmetric synthesis of dapoxetine hydrochloride

• Yijun Zhu,
• Zhenren Liu,
• Hongyan Li,
• Deyong Ye and
• Weicheng Zhou

Beilstein J. Org. Chem. 2015, 11, 2641–2645, doi:10.3762/bjoc.11.283

• ., Shanghai 201203, China 10.3762/bjoc.11.283 Abstract A novel and practical asymmetric synthesis of dapoxetine hydrochloride by using the chiral auxiliary (S)-tert-butanesulfinamide was explored. The synthesis was concise, mild, and easy to perform. The overall yield and stereoselectivity were excellent

• . Keywords: asymmetric synthesis; dapoxetine hydrochloride; stereoselectivity; (S)-tert-butanesulfinamide; Introduction Premature ejaculation (PE) is the most frequent form of ejaculatory dysfunction with a distribution of 39% of the general male population [1][2]. Dapoxetine hydrochloride (1, (S)-(+)-N,N

• acetate aldol reaction [10]. However, these methods are undermined by poor yield, low enantioselectivity, and complex synthetic procedure. Chiral tert-butanesulfinamide, developed by García Ruano and Ellman, has been proven to be a broadly useful reagent for the preparation of chiral amines via the chiral

An investigation of the observed, but counter-intuitive, stereoselectivity noted during chiral amine synthesis via N-chiral-ketimines

• Thomas C. Nugent,
• Richard Vaughan Williams,
• Andrei Dragan,
• Alejandro Alvarado Méndez and
• Andrei V. Iosub

Beilstein J. Org. Chem. 2013, 9, 2103–2112, doi:10.3762/bjoc.9.247

• Scheme 2. (Note: For similar discussions regarding the discrepancy of cis/trans chiral sulfinimine ratios and their corresponding amine product diastereomeric excesses, albeit using hydride reagents for the reduction, see the use of the (S)- and (R)-(+)-tert-butanesulfinamide (t-BuS(O)NH2) auxiliary

A novel asymmetric synthesis of cinacalcet hydrochloride

• Veera R. Arava,
• Laxminarasimhulu Gorentla and
• Pramod K. Dubey

Beilstein J. Org. Chem. 2012, 8, 1366–1373, doi:10.3762/bjoc.8.158

• )-tert-butanesulfinamide and regioselective N-alkylation of the naphthyl ethyl sulfinamide intermediate is described. Keywords: asymmetric synthesis; (R)-tert-butanesulfinamide; cinacalcet hydrochloride; naphthyl ethyl sulfinamide; regioselective N-alkylation; Introduction Cinacalcet hydrochloride

• ][16][17][18][19][20]. In our quest to utilize the chiral tert-butanesulfinamides in asymmetric syntheses of chiral amine APIs in an industrial setting [21][22][23], we report a novel asymmetric synthesis of 1 (Scheme 1) based on (R)-tert-butanesulfinamide (2), which was developed and extensively

• procedures for 1 (Scheme 7). Finally, hydrolysis of 7 dissolved in MTBE with conc. HCl at ambient temperature liberated the pure 1 (Scheme 8). Conclusion In summary, a novel stereoselective and short synthesis of (R)-cinacalcet hydrochloride by the application of (R)-tert-butanesulfinamide and regioselective