In here we present the deoxygenation of the chalcogen oxides EO
(E = S, Se) with R-P(PMe
), so-called phospha-Wittig reagents. The reaction of DABSO (DABCO·2SO
) with R-P(PMe
) (R = Mes*, 2,4,6-
Bu
...-C
H
;
Ter, 2,6-(2,4,6-Me
-C
H
)
-C
H
) resulted in the formation of thiadiphosphiranes (RP)
S (1:R), while selenadiphosphiranes (RP)
Se (2:R) were afforded with SeO
, both accompanied by the formation of OPMe
. Utilizing the sterically more encumbered
Ter-P(PMe
) (
Ter = 2,6-(2,6-iPr
-C
H
)
-C
H
) a different selectivity was observed and (
TerP)
Se (2:DipTer) along with Se(μ-P
Ter)
(3:DipTer) were isolated as the Se-containing species in the reaction with SeO
. Interestingly, the reaction with DABSO (or with equimolar ratios of SeO
at elevated temperatures) gave rise to the formation of the OPMe
-stabilized dioxophosphorane (phosphinidene dioxide)
TerP(O)
-OPMe
(4:DipTer) as the main product. This contrasting reactivity can be rationalized by two potential pathways in the reaction with EO
: (i) a Wittig-type pathway and (ii) a pathway involving oxygenation of the phospha-Wittig reagents and release of SO. Thus, phospha-Wittig reagents are shown to be useful synthetic tools for the metal-free deoxygenation of EO
(E = S, Se).
The commercially available and experimentally convenient (bp 65 °C) difluoromethyltrimethylsilane (TMSCHF
) is proposed as a valuable difluoromethylating transfer reagent for delivering the CHF
...moiety to various heteroatom-based electrophiles. Upon activation with an alkoxide, a conceptually intuitive nucleophilic displacement directly furnishes in high yields the bench-stable analogues.
A practical continuous flow protocol has been developed using readily accessible N-(tert-butylsulfinyl)-bromoimine and Grignard reagents, providing various functionalized piperidines (34 examples) in ...superior results (typically >80% yield and with >90:10 dr) within minutes. The high-performance scale-up is smoothly carried out, and efficient synthesis of the drug precursor further showcases its utility. This flow process offers rapid and scalable access to enantioenriched α-substituted piperidines.
The use of mixed aliphatic organozinc reagents in the multicomponent Mannich reaction is described. A large variety of primary, secondary, and tertiary organozinc reagents, secondary amines and ...aromatic or aliphatic aldehydes could be used for the straightforward preparation of densely substituted amines. The three-component reaction could additionally be performed starting from alkyl halides under reductive (Barbier-type) conditions.
We recently developed 'cellular' reagents-lyophilized bacteria overexpressing proteins of interest-that can replace commercial pure enzymes in typical diagnostic and molecular biology reactions. To ...make cellular reagent technology widely accessible and amenable to local production with minimal instrumentation, we now report a significantly simplified method for preparing cellular reagents that requires only a common bacterial incubator to grow and subsequently dry enzyme-expressing bacteria at 37°C with the aid of inexpensive chemical desiccants. We demonstrate application of such dried cellular reagents in common molecular and synthetic biology processes, such as PCR, qPCR, reverse transcription, isothermal amplification, and Golden Gate DNA assembly, in building easy-to-use testing kits, and in rapid reagent production for meeting extraordinary diagnostic demands such as those being faced in the ongoing SARS-CoV-2 pandemic. Furthermore, we demonstrate feasibility of local production by successfully implementing this minimized procedure and preparing cellular reagents in several countries, including the United Kingdom, Cameroon, and Ghana. Our results demonstrate possibilities for readily scalable local and distributed reagent production, and further instantiate the opportunities available via synthetic biology in general.
Selectively fluorinated molecules are important as materials, pharmaceuticals, and agrochemicals, but their synthesis by simple, mild, laboratory methods is challenging. We report a straightforward ...method for the cross-coupling of aryl and vinyl iodides with a difluoromethyl group generated from readily available reagents to form difluoromethylarenes and difluoromethyl-substituted alkenes. The reaction of electron-neutral, electron-rich, and sterically hindered aryl and vinyl iodides with the combination of CuI, CsF and TMSCF2H leads to the formation of difluoromethyl-substituted products in high yield with good functional group compatibility. This transformation is surprising, in part, because of the prior observation of the instability of CuCF2H.
The difluoromethyl group plays an important role in modern medicinal and agrochemistry. While several difluoromethylation reagents have been reported, these typically rely on difluoromethyl carbenes ...or anions, or target specific processes. Here, we describe a conceptually unique and general process for O-H, N-H and C-H difluoromethylation that involves the formation of a transient dithiole followed by facile desulfurative fluorination using silver(I) fluoride. We also introduce the 5,6-dimethoxy-1,3-benzodithiole (DMBDT) function, which undergoes sufficiently rapid desulfurative fluorination to additionally support
F-difluoromethylation. This new process is compatible with the wide range of functional groups typically encountered in medicinal chemistry campaigns, and the use of Ag
F is demonstrated in the production of
F-labeled derivatives of testosterone, perphenazine, and melatonin, 58.0±2.2, 20.4±0.3 and 32.2±3.6 MBq μmol
, respectively. We expect that the DMBDT group and this
F/
F-difluoromethylation process will inspire and support new efforts in medicinal chemistry, agrochemistry and radiotracer production.
We report herein a facile strategy to synthesize trifluoromethylated γ-lactams through trifluoromethylcarbonylation of
-cyano alkenes using readily available CF
SO
Na as the CF
radical source. A ...range of trifluoromethyl-containing γ-lactams was obtained in good yields. This transition-metal-free protocol is demonstrated with mild conditions, broad substrate scope, good functional group tolerance, convenient reagents, and an easy-to-handle operating system.
Herein, a donor–acceptor–donor (D-A-D) structured small molecule (DPP-TPA) is designed and synthesized for photoacoustic imaging (PAI) guided photodynamic/photothermal synergistic therapy. In the ...diketopyrrolopyrrole (DPP) molecule, a thiophene group is contained to increase the intersystem crossing (ISC) ability through the heavy atom effect. Simultaneously, triphenylamine (TPA) is introduced for bathochromic shift absorption as well as charge transport capacity enhancement. After formation of nanoparticles (NPs, ∼76 nm) by reprecipitation, the absorption of DPP-TPA NPs further displays obvious bathochromic-shift with the maximum absorption peak at 660 nm. What’s more, the NPs architecture enhances the D-A-D structure, which greatly increases the charge transport capacity and impels the charge to generate heat by light. DPP-TPA NPs present high photothermal conversion efficiency (η = 34.5%) and excellent singlet oxygen (1O2) generation (ΦΔ = 33.6%) under 660 nm laser irradiation. PAI, with high spatial resolution and deep biotissue penetration, indicates DPP-TPA NPs can rapidly target the tumor sites within 2 h by the enhanced permeability and retention (EPR) effect. Importantly, DPP-TPA NPs could effectively hinder the tumor growth by photodynamic/photothermal synergistic therapy in vivo even at a low dosage (0.2 mg/kg) upon laser irradiation (660 nm 1.0 W/cm2). This study illuminates the photothermal conversion mechanism of small organic NPs and demonstrates the promising application of DPP-TPA NPs in PAI guided phototherapy.
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