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1. Construction of Diazo Compounds via Catalytic [3 + 2] Annulation of Vinyldiazoacetates and Their Synthetic Applications

   https://doi.org/10.1021/acscatal.4c01291  

   Bao, Ming; Navarrete_Carriola, Diana Victoria; Wherritt, Daniel; Doyle, Michael P (May 2024, ACS Catalysis)

   Highly selective formal [3 + 2]-cycloaddition of vinyldiazoacetates with quinone ketals and quinoneimine ketals has been accomplished at room temperature with catalytic amounts of the Brønsted acid triflimide, leading to highly functionalized diazoacetates in good yields. The vinyldiazonium ion generated by electrophilic addition to the vinylogous position of the reactant vinyldiazo compound is the key intermediate in this selective transformation. Both oximidovinyldiazoacetates and those with other vinyl substituents undergo cycloaddition reactions with quinone ketals whose products, after extended reaction times, undergo substrate-dependent 1,2-migration; catalysis by Rh2(OAc)4, HNTf2, and Sc(OTf)3 effects these 1,2-migrations to the same products. However, the products from HNTf2-catalyzed reactions between quinoneimine and oximidovinyldiazoacetates undergo Rh2(OAc)4-catalyzed 1,3-C−H insertion. 1,3-Difunctionalization products are obtained for electrophilic reactions of Eschenmoser’s salt with selected vinyldiazoacetates, but with α-dibenzylaminomethyl ether, 1,6-hydride transfer reactions are observed with oximidovinyldiazoacetates. 

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2. Diastereoselective Synthesis of (3R,5R)-γ-Hydroxypiperazic Acid

   https://doi.org/10.1055/s-0040-1719824  

   Gerrein, Taylor A.; Elbatrawi, Yassin M.; Del Valle, Juan R. (October 2021, Synlett)

   Abstract We report an asymmetric synthesis of the (3R,5R)-γ-hydroxypiperazic acid (γ-OHPiz) residue encountered in several bioactive nonribosomal peptides. Our strategy relies on a diastereoselective enolate hydroxylation reaction and electrophilic N-amination to provide the acyclic γ-OHPiz precursor. This orthogonally protected α-hydrazino acid intermediate is amenable to late-stage diazinane ring formation following incorporation into a peptide chain. We determined the N-terminal amide rotamer propensity of the γ-OHPiz residue and showed that the γ-OH substituent enhances trans-amide bias relative to piperazic acid. 

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3. Enhanced Reactivity for Aromatic Bromination via Halogen Bonding with Lactic Acid Derivatives

   https://doi.org/10.1021/acs.joc.2c00611  

   Baker, Sarah I.; Yaghoubi, Mahshid; Bidwell, Samantha L.; Pierce, Savannah L.; Hratchian, Hrant P.; Baxter, Ryan D. (June 2022, The Journal of Organic Chemistry)

   We report a new method for regioselective aromatic bromination using lactic acid derivatives as halogen bond acceptors with N-bromosuccinimide (NBS). Several structural analogues of lactic acid affect the efficiency of aromatic brominations, presumably via Lewis acid/base halogen-bonding interactions. Rate comparisons of aromatic brominations demonstrate the reactivity enhancement available via catalytic additives capable of halogen bonding. Computational results demonstrate that Lewis basic additives interact with NBS to increase the electropositive character of bromine prior to electrophilic transfer. An optimized procedure using catalytic mandelic acid under aqueous conditions at room temperature was developed to promote aromatic bromination on a variety of arene substrates with complete regioselectivity. 

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4. Study of conditions for streamlined assembly of a model bacteriochlorophyll from two dihydrodipyrrin halves

   https://doi.org/10.1039/d0nj04855k  

   Nguyen, Khiem Chau; Wang, Pengzhi; Lindsey, Jonathan S. (January 2021, New Journal of Chemistry)

   null (Ed.)

   A long-term goal is to gain synthetic access to native photosynthetic bacteriochlorophylls. A recently developed route entails Knoevenagel condensation of an AD dihydrodipyrrin ( I , bearing a carboxaldehyde attached to pyrroline ring D) and a BC dihydrodipyrrin ( II , bearing a β-ketoester attached to pyrrole ring C) to form the Z / E -enone. Acid-mediated double-ring closure of the E -enone III-E (Nazarov cyclization, electrophilic aromatic substitution, and elimination of methanol) affords the bacteriochlorophyll skeleton BC-1 containing the isocyclic ring (ring E), a trans -dialkyl group in ring D, and a gem-dimethyl group in ring B. Prior work established the synthesis and the integrity of the resulting trans -dialkyl groups and bacteriochlorin chromophore. The counterpart report here concerns an in-depth study of conditions for the double-ring closure: catalyst/solvent surveys; grid search including time courses of [ III-E ] versus [acid] concentrations emphasizing equimolar, inverse molar, and variable acid lines of inquiry; and chlorin byproduct quantitation. Key findings are that (1) the double-ring closure can be carried out in 4 h ( t 1/2 ∼ 40 min) instead of 20 h, affording ∼1/5th the chlorin byproduct (0.16%) while maintaining the yield of BC-1 (up to 77%); (2) the separate Z / E -enones of III have comparable reactivity; (3) sub-stoichiometric quantities of acid are ineffective; (4) the Knoevenagel condensation (40 mM, room temperature, piperidine/acetic acid in acetonitrile) and the acid-mediated double-ring closure (0.20 mM, 80 °C, Yb(OTf) 3 in acetonitrile) can be carried out in a two-step process; and (5) zinc insertion to form ZnBC-1 is straightforward. Together, the results enable streamlined conversion of dihydrodipyrrin reactants to the bacteriochlorophyll model compounds. 

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5. Highly Chemoselective Transamidation of Unactivated Tertiary Amides by Electrophilic N−C(O) Activation by Amide‐to‐Acyl Iodide Re‐routing

   https://doi.org/10.1002/anie.202202794  

   Zuo, Dongxu; Wang, Qun; Liu, Long; Huang, Tianzeng; Szostak, Michal; Chen, Tieqiao (April 2022, Angewandte Chemie International Edition)

   Abstract The challenging transamidation of unactivated tertiary amides has been accomplished via cooperative acid/iodide catalysis. Most crucially, the method provides a novel manifold to re‐route the reactivity of unactivated N,N‐dialkyl amides through reactive acyl iodide intermediates, thus reverting the classical order of reactivity of carboxylic acid derivatives. This method provides a direct route to amide‐to‐amide bond interconversion with excellent chemoselectivity using equivalent amounts of amines. The combination of acid and iodide has been identified as the essential factor to activate the amide C−N bond through electrophilic catalytic activation, enabling the production of new desired transamidated products with wide substrate scope of both unactivated amides and amines, including late‐stage functionalization of complex APIs (>80 examples). We anticipate that this powerful activation mode of unactivated amide bonds will find broad‐ranging applications in chemical synthesis. 

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