18880-00-7Relevant articles and documents
Stereochemistry of solvation of benzylic lithium compounds: Structure and dynamic behavior
Fraenkel, Gideon,Duncan, Joseph H.,Martin, Kevin,Wang, Jinhai
, p. 10538 - 10544 (1999)
Several sec-benzylic lithium compounds, both externally coordinated, [α-(trimethylsilyl)benzyl]-lithium·PMDTA (12) and p-tert-butyl-α-(dimethylethylsilyl)benzyllithium·TMEDA (13), and internally coordinated, [α-[[[cis-2,5-bis(methoxymethyl)-1-pyrrolidinyl]methyl]dimethylsilyl]-p- tert-butylbenzyl]lithium (14) and [α-[[[(S)-2-(methoxymethyl)-1-pyrrolidinyl]methyl]dimethylsilyl]benzyl] lithium (15), have been prepared. Ring 13C NMR shifts indicate that 12-15 have partially delocalized structures. Externally solvated allylic lithium compounds are found to be delocalized, and only some internally coordinated species are partially delocalized. Compound 15 exists as > 95% of one stereoisomer of the two invertomers at Cα. This is in accord with a published ee of > 98% in products of the reactions of 15 with aldehydes. All four compounds show evidence of one-bond 13C-6Li spin coupling, ca. 3 Hz, which indicates a small detectable C-Li covalence. Averaging of the 13C-6Li coupling of 12 with increasing temperature provides the dynamics of intermolecular C-Li bond exchange, with ΔH?ex = 9 ± 0.5 kcal mol-1. Carbon-13 NMR line shape changes due to geminal methyls, and ligand carbons gave similar rates of inversion at Cα in 13 (externally solvated) and 14 (internally solvated), ΔH?inv ≈ 4.9 ± 0.5 kcal mol-1. By contrast, barriers to rotation around the ring-Cα bonds vary widely, depending on the mode of lithium coordination, ΔH?rot ≈ 8 ± 0.5 to 19 ± 1.0 kcal mol-1. Some mechanisms for these processes are proposed.
Readily Reconfigurable Continuous-Stirred Tank Photochemical Reactor Platform
Blacker, A. John,Francis, Daniel,Kapur, Nikil,Marsden, Stephen P.
supporting information, (2022/01/12)
A new modular photochemical continuous stirred-tank reactor (CSTR) design is described, based upon the development of light-source units that can be fitted to the previously described fReactor CSTR platform. In addition to use in homogeneous photochemical reactions (e.g., photoredox-catalyzed hydroamination), these units are especially well suited to handling multiphasic mixtures, exemplified here in solid-liquid (Wohl-Ziegler bromination) and gas-liquid (photocatalytic oxidative decarboxylation) reactions. The use of slurries as input feeds allows for the intensification of photochemical brominations, while the modular nature of the system facilitates the simple integration of downstream reaction steps, exemplified here in a continuous synthesis of an intermediate for the antihypertensive drug valsartan.
Photochemical benzylic bromination in continuous flow using BrCCl3 and its application to telescoped p-methoxybenzyl protection
Otake, Yuma,Williams, Jason D.,Rincón, Juan A.,De Frutos, Oscar,Mateos, Carlos,Kappe, C. Oliver
supporting information, p. 1384 - 1388 (2019/02/14)
BrCCl3 represents a rarely used benzylic brominating reagent with complementary reactivity to other reagents. Its reactivity has been revisited in continuous flow, revealing compatibility with electron-rich aromatic substrates. This has brought about the development of a p-methoxybenzyl bromide generator for PMB protection, which was successfully demonstrated on a pharmaceutically relevant intermediate on 11 g scale, giving 91% yield and a PMB-Br space-time-yield of 1.27 kg L?1 h?1
Systematic Evaluation of Sulfoxides as Catalysts in Nucleophilic Substitutions of Alcohols
Motsch, Sebastian,Schütz, Christian,Huy, Peter H.
supporting information, p. 4541 - 4547 (2018/09/13)
Herein, a method for the nucleophilic substitution (SN) of benzyl alcohols yielding chloro alkanes is introduced that relies on aromatic sulfoxides as Lewis base catalysts (down to 1.5 mol-%) and benzoyl chloride (BzCl) as reagent. A systematic screening of various sulfoxides and other sulfinyl containing Lewis bases afforded (2-methoxyphenyl)methyl sulfoxide as optimal catalyst. In contrast to reported formamide catalysts, sulfoxides also enable the application of plain acetyl chloride (AcCl) as reagent. In addition, it was demonstrated that weakly electrophilic carboxylic acid chlorides like BzCl promote Pummerer rearrangement of sulfoxides already at room temperature. This side-reaction also provided the explanation, why sulfoxide catalyzed SN-reactions of alcohols do not allow the effective production of aliphatic and electron deficient chloro alkanes. Comparison experiments provided further insight into the reaction mechanism.
