Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• . Control experiments confirmed the necessity of both AIBN and DTBP, with higher temperatures favoring the desired cyclization over side reactions. In 2021, a novel excited-state palladium-catalyzed alkylation/annulation reaction was developed to achieve reaction of unactivated alkyl chlorides, facilitating

• enables the generation of alkyl radicals from alkyl chlorides, thus broadening the scope of substrates available for cross-coupling reactions. The substrate scope was thoroughly investigated, demonstrating broad compatibility with various N-methyl-N-phenylmethacrylamides and unactivated alkyl chlorides

• . Primary, secondary, and tertiary alkyl chlorides participated efficiently in the reaction, yielding 3,3-disubstituted oxindoles 81a–h in moderate to excellent yields of 40–92%. Notably, multichlorinated compounds, such as dichloromethane (DCM) and chloroform (CHCl₃), also served as effective alkylating

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• reduced electrophilicity of the ester carbonyl. In 2021, Dong and Xie reported the development of an azido Matteson reaction, which achieves carbene insertion into an N–B bond of aminoboranes 84 or 86 (Scheme 22) [53]. In this methodology, by controlling the carbene leaving group (alkyl chlorides/alkyl

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• hydrochlorinations, followed by metal-promoted radical hydrochlorinations, and concludes with a brief overview of recent anti-Markovnikov hydrochlorinations. Keywords: addition reactions; alkenes; alkyl chlorides; hydrochlorination; Markovnikov; Introduction The hydrochlorination of alkenes dates back to its

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• modified synthetic procedure [14]. Here, it was included the chromatographic purification of the final chloroformates, which led to removing of corresponding alkyl chlorides formed as byproducts. The aldehyde 17 was prepared by a different way, because the acid-catalyzed hydrolysis of its acetal

Mechanistic studies of the solvolysis of alkanesulfonyl and arenesulfonyl halides

• Malcolm J. D’Souza and
• Dennis N. Kevill

Beilstein J. Org. Chem. 2022, 18, 120–132, doi:10.3762/bjoc.18.13

• H2O or D2O based on very accurate specific rate measurements was possible. The ksie for the hydrolysis of alkyl chlorides is usually in the range of 1.20 to 1.25 which, at 20 °C, increases to values of 1.568 ± 0.006 and 1.564 ± 0.006 for methanesulfonyl chloride and benzenesulfonyl chloride [28]. This

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• tolerated various electron-rich and electron-poor substituents, affording exclusively benzylic C(sp3)–H gem-difluorinated products in modest to excellent (33–95%) yield of 28b–h. The functional group tolerance was demonstrated by successful reactions of alkyl chlorides, ketones and a para-substituted MIDA

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• best of our knowledge, there were no reports on using BTMS for the nucleophilic substitution of alkyl chlorides. A similar exchange reaction was reported only for 2-chloropyridines [51], and required harsh reaction conditions, such as heating at 90–100 °C for 100 h. In this study we investigated the

Disposable cartridge concept for the on-demand synthesis of turbo Grignards, Knochel–Hauser amides, and magnesium alkoxides

• Mateo Berton,
• Kevin Sheehan,
• Andrea Adamo and
• D. Tyler McQuade

Beilstein J. Org. Chem. 2020, 16, 1343–1356, doi:10.3762/bjoc.16.115

• stratified packed-bed columns containing magnesium and LiCl Objective: To generate organomagnesium–lithium chloride complexes (turbo Grignards) from alkyl chlorides using a stratified bicomponent packed-bed column composed of magnesium metal and lithium chloride. Challenges: Metal passivation by lithium

• ability to safely produce high-quality organomagnesium reagents on demand. Conclusion We have developed a new flow setup for the on-demand synthesis of highly concentrated (≈2 M) turbo Grignards from alkyl chlorides using a stratified packed-bed column of activated magnesium and lithium chloride. The

• possible to directly use the hygroscopic LiCl in a solid form. The back-pressure control allows a high-temperature oxidative addition reaction and enables the quantitative conversion of less reactive but more cost-effective alkyl chlorides. Furthermore, a low-cost pod-style synthesizer prototype has been

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• the synthesis of acyclic nucleoside phosphonates including mesylates [42], tosylates [16][43][44] and alkyl chlorides [45][46][47][48][49][50][51]. Alkylation reactions conducted with these electrophiles generally require higher temperatures. Furthermore, these reagents typically afford products in

Synthesis of 1-indanones with a broad range of biological activity

• Marika Turek,
• Dorota Szczęsna,
• Marek Koprowski and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2017, 13, 451–494, doi:10.3762/bjoc.13.48

• useless in vivo. However, considering the enormous potential of abicoviromycin, syntheses of its additional analogs are reasonable. 1.3 From alkyl chlorides Radiolabeled tracers can supply precious information about structures of biocatalytic reaction networks. The [14C]1-indanone 175 has been used in the

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

Glycosylation efficiencies on different solid supports using a hydrogenolysis-labile linker

• Mayeul Collot,
• Steffen Eller,
• Markus Weishaupt and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2013, 9, 97–105, doi:10.3762/bjoc.9.13

• resins by amide-bond formation (Scheme 4, Supporting Information File 1). In the next step, the alkyl chlorides were displaced by the cesium carboxylate of 1. Resin loadings were determined by Fmoc quantification (Table 1). Glycosylations on functionalized solid supports 30–33 were performed on the

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

• Magnus Rueping and
• Boris J. Nachtsheim

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

• environmentally and economically benign processes, the development of FC reactions using only catalytic amounts of a metal or acid catalyst would be highly desirable. In addition, the substitution of the alkyl chlorides by other, less toxic, alkylating reagents such as alcohols would be a major improvement as