Construction of CF₂ moieties in FDA-approved drugs (2016–2025): industrial routes, mechanisms, and scale-up considerations

• Wenyan Yao,
• Huanhuan Zhang,
• Xiaolong Yang and
• Feng Liu

Beilstein J. Org. Chem. 2026, 22, 1122–1150, doi:10.3762/bjoc.22.91

• primary alcohol steps. Routes b–d (reported in 2022) [9] all employed building block 23 to introduce the CF2 group, with route d being the industrial route. Using 23 and tert-butylsulfinamide (77), the chiral nitrogen center was constructed under Ti(OEt)4 catalysis under different conditions: using

• . First, compound 84 formed an imine with (S)-tert-butylsulfinamide quantitatively in the presence of copper sulfate, which was then added to 85, followed by reduction with magnesium turnings to introduce the CF2 group. The addition step was clean, with no minor isomer detected, but required −78 °C and

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• -II) afforded the corresponding 17-spirolactams 123a,b in 71–73% yield (Scheme 34). Notably, when (S)-(+)-tert-butylsulfinamide was used in the initial step of the reaction sequence, the allylation of the resulting imine proceeded diastereoselectively, yielding the 17-allyl-17-sulfinamido compound as

• potentially favourable profile for prostate cancer therapy. Spirolactam steroids Steroidal spirolactams were obtained by Fousteris et al. in a five-step reaction sequence from 3β-benzyloxy-12β-hydroxydehydroepiandrosterone (118) [59]. The protected DHEA derivative was initially condensed with (R)-(+)-tert

• -butylsulfinamide, leading to the formation of the imine 119. Subsequent reaction with allylmagnesium bromide yielded a mixture of 17-allyl 17-sulfonamido derivatives 120a,b in a 2.5:1 diastereomeric ratio (17S:17R), which were isolated and treated separately. Acid treatment of the sulfinamides 120a,b resulted in

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

•  5). Product (RS)-14b (85:15 dr), i.e., a mixture of two enantiomerically pure diastereomers, was obtained from (RS)-tert-butylsulfinamide upon allylation with tert-butyl α-(bromomethyl)acrylate followed by 1,4-addition with Et2Zn. It was then converted into the known β2-amino acid 17 by TFA-promoted

• informative. As discussed previously (Scheme 4), application of the developed protocol for 1,4-addition to 10 only yields N-benzyl-N-tert-butylsulfinamide following β-elimination. By contrast, in the presence of benzaldehyde, 1,4-addition–aldol condensation is predominant, yielding 26 in 56% yield as a 49:25

• of primary amines and tert-butylsulfinamide (preparation of compounds 5–7 and 8a–c). In a round-bottomed flask under argon, n-BuLi (1.0 equiv, soln. in heptane) was added dropwise to a THF (0.2 mol·L−1) solution of the appropriate primary amine or tert-butylsulfinamide (1.0 equiv) at −55 °C. The

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

• -benzyl-6,7-dimethoxy-N-methyl-1,2,3,4-tetrahydroisoquinoline (164), (−)-O,O-dimethylcoclaurine (165) and (+)-O-methylarmapavine (166) alkaloids via chiral tert-butylsulfinamide through a haloamide cyclization. The strategy was based on the addition of organomagnesium bromide or chloride to chiral N

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• provided the desired 5-hydroxypentanenitrile and THF in the ratio 5:2 (monitored by 1H NMR spectroscopy, see Supporting Information File 1). Next, 4-cyanobutan-1-ol was oxidized in a Swern oxidation and the resulting aldehyde was condensed with tert-butylsulfinamide (S)-1, according to GP-2. The reaction

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• supported by the IR spectrum. Only one S=O vibration can be identified at 1098 cm−1, in a similar position as the S=O vibrations in DMSO (1050 cm−1) or tert-butylsulfinamide (1032 cm−1) [43]. The strong band at about 1330 cm−1, typical for the asymmetric S=O stretch in sulfonamides and sulfones, is absent

Thermal rearrangement of tert-butylsulfinamide

• Veera Reddy Arava,
• Laxminarasimhulu Gorentla and
• Pramod Kumar Dubey

Beilstein J. Org. Chem. 2011, 7, 9–12, doi:10.3762/bjoc.7.2

• above room temperature, and in chlorinated solvents they undergo rearrangement to form the more stable N-(tert-butylthio)-tert-butylsulfonamide. Keywords: chlorinated solvents; N-(tert-butylthio)-tert-butylsulfonamide; tert-butylsulfinamide; thermal rearrangement; Introduction Over the past decade, an

• ever increasing number of methods based upon the chiral amine reagent tert-butylsulfinamide (1) (Figure 1) has become one of the most extensively used synthetic approaches for both the production and discovery of drug candidates [1]. In particular, the tert-butylsulfinyl group showed high levels of

• room temperature and in chlorinated solvents. Experimental See Supporting Information File 1 for full experimental data. tert-Butylsulfinamide. N-(tert-butylthio)-tert-butylsulfonamide. ORTEP diagram of 3. Synthesis of acid amide. Chemical synthesis of 3. Synthesis of tert-butylsulfanyl chloride