13002-65-8Relevant academic research and scientific papers
Rh-Catalyzed Coupling of Aldehydes with Allylboronates Enables Facile Access to Ketones
Zhang, Kezhuo,Huang, Jiaxin,Zhao, Wanxiang
supporting information, (2022/02/21)
We present herein a novel strategy for the preparation of ketones from aldehydes and allylic boronic esters. This reaction involves the allylation of aldehydes with allylic boronic esters and the Rh-catalyzed chain-walking of homoallylic alcohols. The key to this successful development is the protodeboronation of alkenyl borylether intermediate via a tetravalent borate anion species in the presence of KHF2 and MeOH. This approach features mild reaction conditions, broad substrate scope, and excellent functional group tolerance. Mechanistic studies also supported that the tandem allylation and chain-walking process were involved.
Stereoconvergent and -divergent synthesis of tetrasubstituted alkenes by nickel-catalyzed cross-couplings
Zell, Daniel,Kingston, Cian,Jermaks, Janis,Smith, Sleight R.,Seeger, Natalie,Wassmer, Jana,Sirois, Lauren E.,Han, Chong,Zhang, Haiming,Sigman, Matthew S.,Gosselin, Francis
supporting information, p. 19078 - 19090 (2021/11/22)
We report the development of a method to diastereoselectively access tetrasubstituted alkenes via nickel-catalyzed Suzuki-Miyaura cross-couplings of enol tosylates and boronic acid esters. Either diastereomeric product was selectively accessed from a mixture of enol tosylate starting material diastereomers in a convergent reaction by judicious choice of the ligand and reaction conditions. A similar protocol also enabled a divergent synthesis of each product isomer from diastereomerically pure enol tosylates. Notably, high-throughput optimization of the monophosphine ligands was guided by chemical space analysis of the kraken library to ensure a diverse selection of ligands was examined. Stereoelectronic analysis of the results provided insight into the requirements for reactive and selective ligands in this transformation. The synthetic utility of the optimized catalytic system was then probed in the stereoselective synthesis of various tetrasubstituted alkenes, with yields up to 94% and diastereomeric ratios up to 99:1 Z/E and 93:7 E/Z observed. Moreover, a detailed computational analysis and experimental mechanistic studies provided key insights into the nature of the underlying isomerization process impacting selectivity in the cross-coupling.
Pd-catalyzed cross-coupling of highly sterically congested enol carbamates with grignard reagents via c-o bond activation
Chen, Zicong,So, Chau Ming
, p. 3879 - 3883 (2020/06/08)
The palladium-catalyzed cross-coupling reaction of enol carbamates to construct highly sterically congested alkenyl compounds is presented for the first time. This protocol demonstrates the potential of using thermally stable and highly atom-economic enol electrophiles as building blocks in bulky alkene synthesis. This reaction accommodates a broad substrate scope with excellent Z/E isomer ratios, which also provides a new synthetic pathway for accessing Tamoxifen.
Iterative synthesis of alkenes by insertion of lithiated epoxides into boronic esters
Bojaryn, Kevin,Fritsch, Stefan,Hirschhaüser, Christoph
supporting information, p. 2218 - 2222 (2019/04/10)
The insertion of lithiated epoxides into boronic esters followed by thermal syn-elimination provides a stereospecific entry to alkenes. This process avoids transition metals and is amenable to iteration to provide higher substitution patterns.
An atom efficient synthesis of tamoxifen
Heijnen, Dorus,Van Zuijlen, Milan,Tosi, Filippo,Feringa, Ben L.
supporting information, p. 2315 - 2320 (2019/03/06)
The direct carbolithiation of diphenylacetylenes and their cross-coupling procedure taking advantage of the intermediate alkenyllithium reagents are presented. By employing our recently discovered highly active palladium nanoparticle based catalyst, we were able to couple an alkenyllithium reagent with a high (Z/E) selectivity (10:1) and good yield to give the breast cancer drug tamoxifen in just 2 steps from commercially available starting materials and with excellent atom economy and reaction mass efficiency.
Photoredox-Catalyzed C-H Arylation of Internal Alkenes to Tetrasubstituted Alkenes: Synthesis of Tamoxifen
Wang, Quannan,Yang, Xiaoge,Wu, Ping,Yu, Zhengkun
supporting information, p. 6248 - 6251 (2017/11/24)
Visible-light-induced direct C-H arylation of S,S-functionalized internal alkenes, that is, α-oxo ketene dithioacetals and analogues, has been efficiently realized with aryldiazonium salts (ArN2BF4) as coupling partners and Ru(bpy)s
Photochemical Activation of Tertiary Amines for Applications in Studying Cell Physiology
Asad, Naeem,Deodato, Davide,Lan, Xin,Widegren, Magnus B.,Phillips, David Lee,Du, Lili,Dore, Timothy M.
supporting information, p. 12591 - 12600 (2017/09/23)
Representative tertiary amines were linked to the 8-cyano-7-hydroxyquinolinyl (CyHQ) photoremovable protecting group (PPG) to create photoactivatable forms suitable for use in studying cell physiology. The photoactivation of tamoxifen and 4-hydroxytamoxifen, which can be used to activate Cre recombinase and CRISPR-Cas9 gene editing, demonstrated that highly efficient release of bioactive molecules could be achieved through one- and two-photon excitation (1PE and 2PE). CyHQ-protected anilines underwent a photoaza-Claisen rearrangement instead of releasing amines. Time-resolved spectroscopic studies revealed that photorelease of the tertiary amines was extremely fast, occurring from a singlet excited state of CyHQ on the 70 ps time scale.
Divergent Synthetic Access to E- and Z-Stereodefined All-Carbon-Substituted Olefin Scaffolds: Application to Parallel Synthesis of (E)- and (Z)-Tamoxifens
Ashida, Yuichiro,Honda, Atsushi,Sato, Yuka,Nakatsuji, Hidefumi,Tanabe, Yoo
, p. 73 - 89 (2017/02/10)
A highly substrate-general synthesis of all-carbon-substituted E- and Z-stereodefined olefins is performed. The method comprises two sets of parallel and stereocomplementary preparations of (E)- and (Z)-α,β-unsaturated esters involving two robust and distinctive reactions: 1) stereocomplementary enol tosylations using readily available TsCl/diamine/(LiCl) base reagents, and 2) stereoretentive Negishi cross-coupling using the catalysts [Pd(dppe)Cl2] (for E) and [Pd(dppb)Cl2] (for Z). The present parallel approach is categorized as both type I (convergent approach: 16 examples, 56–87 % yield) and type II (divergent approach: 18 examples, 70–95 % yield). The obtained (E)- and (Z)-α,β-unsaturated ester scaffolds are successfully transformed into various E- and Z-stereodefined known and novel olefins (8×2 derivatization arrays). As a demonstration, application to the parallel synthesis of both (E)- and (Z)-tamoxifens, a representative motif of all-carbon-substituted olefins, is accomplished in a total of eight steps with an overall yield of 58 % (average 93 %) and 57 % (average 93 %), respectively.
Transition-Metal-Free α-Arylation of Enolizable Aryl Ketones and Mechanistic Evidence for a Radical Process
Pichette Drapeau, Martin,Fabre, Indira,Grimaud, Laurence,Ciofini, Ilaria,Ollevier, Thierry,Taillefer, Marc
, p. 10587 - 10591 (2015/09/02)
The α-arylation of enolizable aryl ketones can be carried out with aryl halides under transition-metal-free conditions using KOtBu in DMF. The α-aryl ketones thus obtained can be used for step- and cost-economic syntheses of fused heterocycles and Tamoxifen. Mechanistic studies demonstrate the synergetic role of base and solvent for the initiation of the radical process.
Nickel-catalyzed three-component domino reactions of aryl grignard reagents, alkynes, and aryl halides producing tetrasubstituted alkenes
Xue, Fei,Zhao, Jin,Hor, T. S. Andy,Hayashi, Tamio
supporting information, p. 3189 - 3192 (2015/03/30)
Three-component reaction of aryl Grignard reagents, alkynes, and aryl halides in the presence of 1 mol % of NiCl2 proceeded sequentially through carbomagnesiation of the alkyne followed by cross-coupling of the resulting alkenyl Grignard reagent with aryl halide to give tetrasubstituted alkenes in high yields.
