A Versatile Room-Temperature Route to Di- and Trisubstituted Allenes Using Flow-Generated Diazo Compounds**

A copper-catalyzed coupling reaction between flow-generated unstabilized diazo compounds and terminal alkynes provides di- and trisubstituted allenes. This extremely mild and rapid transformation is highly tolerant of several functional groups.

[1]  Shichao Yu,et al.  Allene in katalytischer asymmetrischer Synthese und Naturstoffsynthese , 2012 .

[2]  S. Kousar,et al.  Allene formation by gold catalyzed cross-coupling of masked carbenes and vinylidenes , 2007, Proceedings of the National Academy of Sciences.

[3]  S. Ma,et al.  Electrophilic addition and cyclization reactions of allenes. , 2009, Accounts of chemical research.

[4]  Dennis G. Gillingham,et al.  Catalytic X-H insertion reactions based on carbenoids. , 2013, Chemical Society reviews.

[5]  Claudio Battilocchio,et al.  Flow chemistry as a discovery tool to access sp2–sp3 cross-coupling reactions via diazo compounds† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c4sc03072a Click here for additional data file. , 2014, Chemical science.

[6]  A. Maguire,et al.  Taming hazardous chemistry in flow: the continuous processing of diazo and diazonium compounds. , 2015, Chemistry.

[7]  Peter H Seeberger,et al.  Continuous-flow synthesis of the anti-malaria drug artemisinin. , 2012, Angewandte Chemie.

[8]  Shichao Yu,et al.  Allenes in catalytic asymmetric synthesis and natural product syntheses. , 2012, Angewandte Chemie.

[9]  S. Ma,et al.  Cadmium iodide-mediated allenylation of terminal alkynes with ketones , 2013, Nature Communications.

[10]  Steven V. Ley,et al.  Organische Synthese: Vormarsch der Maschinen , 2015 .

[11]  J. Fox,et al.  Copper-catalyzed synthesis of 2,4-disubstituted allenoates from α-diazoesters. , 2011, Organic letters.

[12]  Flavien Susanne,et al.  Continuous flow synthesis. A pharma perspective. , 2012, Journal of medicinal chemistry.

[13]  Jing-yao Liu,et al.  DFT Studies on Cu-Catalyzed Cross-Coupling of Diazo Compounds with Trimethylsilylethyne and tert-Butylethyne: Formation of Alkynes for Trimethylsilylethyne while Allenes for tert-Butylethyne , 2014 .

[14]  D. Frantz,et al.  Recent Advances in the Catalytic Syntheses of Allenes: A Critical Assessment , 2014 .

[15]  Ryan L. Hartman,et al.  Pro und kontra Strömungsreaktoren in der Synthese , 2011 .

[16]  N. Krause,et al.  Synthese und Eigenschaften allenischer Natur‐ und Wirkstoffe , 2004 .

[17]  J. Schwartz,et al.  Organometallics , 1987, Science.

[18]  P. Seeberger,et al.  Kontinuierliche Synthese des Malariawirkstoffs Artemisinin , 2012 .

[19]  Richard J Ingham,et al.  Organic synthesis: march of the machines. , 2015, Angewandte Chemie.

[20]  N. Krause,et al.  Synthesis and properties of allenic natural products and pharmaceuticals. , 2004, Angewandte Chemie.

[21]  Richard J Ingham,et al.  A Systems Approach towards an Intelligent and Self-Controlling Platform for Integrated Continuous Reaction Sequences** , 2014, Angewandte Chemie.

[22]  Ryan L. Hartman,et al.  Deciding whether to go with the flow: evaluating the merits of flow reactors for synthesis. , 2011, Angewandte Chemie.

[23]  Steven V Ley,et al.  Accelerating spirocyclic polyketide synthesis using flow chemistry. , 2014, Angewandte Chemie.

[24]  A. Hashmi,et al.  Modern Allene Chemistry , 2004 .

[25]  J. Wang,et al.  CuI-catalyzed cross-coupling of N-tosylhydrazones with terminal alkynes: synthesis of 1,3-disubstituted allenes. , 2013, The Journal of organic chemistry.

[26]  Shichao Yu,et al.  How easy are the syntheses of allenes? , 2011, Chemical communications.

[27]  J. Wang,et al.  Coupling of N-tosylhydrazones with terminal alkynes catalyzed by copper(I): synthesis of trisubstituted allenes. , 2010, Angewandte Chemie.

[28]  Steven V Ley,et al.  Flow chemistry syntheses of natural products. , 2013, Chemical Society reviews.

[29]  Timothy F Jamison,et al.  A three-minute synthesis and purification of ibuprofen: pushing the limits of continuous-flow processing. , 2015, Angewandte Chemie.

[30]  C. Hayes,et al.  Alkyl halide-free heteroatom alkylation and epoxidation facilitated by a recyclable polymer-supported oxidant for the in-flow preparation of diazo compounds. , 2015, Chemistry.

[31]  J. Wegner,et al.  Flow Chemistry – A Key Enabling Technology for (Multistep) Organic Synthesis , 2012 .

[32]  Steven V Ley,et al.  Flow chemistry meets advanced functional materials. , 2014, Chemistry.

[33]  G. C. Fu,et al.  A straightforward and mild synthesis of functionalized 3-alkynoates. , 2004, Angewandte Chemie.

[34]  F. Diederich,et al.  Allenes in molecular materials. , 2012, Angewandte Chemie.

[35]  James M. B. Evans,et al.  End-to-end continuous manufacturing of pharmaceuticals: integrated synthesis, purification, and final dosage formation. , 2013, Angewandte Chemie.

[36]  F. Diederich,et al.  Allene in molekularen Materialien , 2012 .

[37]  S. Ley,et al.  The rapid synthesis of oxazolines and their heterogeneous oxidation to oxazoles under flow conditions. , 2015, Organic & biomolecular chemistry.

[38]  Richard J Ingham,et al.  Cyclopropanation using flow-generated diazo compounds. , 2015, Organic & biomolecular chemistry.

[39]  Varinder K. Aggarwal,et al.  Science of Synthesis , 2005 .

[40]  A. D. Allen,et al.  Ketenes and other cumulenes as reactive intermediates. , 2013, Chemical reviews.

[41]  C. Wiles,et al.  Continuous flow reactors: a perspective , 2012 .

[42]  T. Wirth,et al.  Diazo compounds in continuous-flow technology. , 2015, ChemSusChem.