Creative approaches towards the synthesis of 2,5-dihydro- furans, thiophenes, and pyrroles. One method does not fit all!

A single method is never sufficient, which is why there is a great need for developing many diverse and creative approaches towards every chemical substrate class. This statement is supported by the contents of this perspective in addition to providing the reader with a helpful synthetic roadmap for selecting a suitable method for the building blocks being discussed. Detailed in this review are eight different synthetic approaches that provide access to valuable 2,5-dihydro- furan, thiophene and pyrrole building blocks. Each approach is briefly presented and its limits discussed. The strengths and weaknesses of each approach are further highlighted with a graphical table summary at the end. This summary clearly drives home the point that for every chemical substrate class we need many good methods in order to provide access to every member of each class.

[1]  S. Hoff,et al.  Base induced reactions of 1‐alkoxy‐ or l‐methylthio‐l‐(α‐ or β‐hydroxyalkyl)allenes. Formation of 3‐alkoxy‐ and 3‐methylthiodihydrofurans , 2010 .

[2]  J. T. Njardarson,et al.  Lewis acid catalyzed [1,3]-sigmatropic rearrangement of vinyl aziridines. , 2008, Organic letters.

[3]  Itaru Osaka,et al.  Advances in molecular design and synthesis of regioregular polythiophenes. , 2008, Accounts of chemical research.

[4]  L. Stanley,et al.  Enantioselective copper-catalyzed 1,3-dipolar cycloadditions. , 2008, Chemical reviews.

[5]  D. Yohannes,et al.  Deconstructing cytisine: The syntheses of (+/-)-cyfusine and (+/-)-cyclopropylcyfusine, fused ring analogs of cytisine. , 2008, Bioorganic & medicinal chemistry letters.

[6]  Ge Zou,et al.  Total synthesis of (-)-salviasperanol. , 2008, Organic letters.

[7]  N. Krause,et al.  Golden opportunities in natural product synthesis: first total synthesis of (-)-isocyclocapitelline and (-)-isochrysotricine by gold-catalyzed allene cycloisomerization. , 2007, Organic & biomolecular chemistry.

[8]  H. Pellissier Asymmetric 1,3-Dipolar Cycloadditions , 2007 .

[9]  Ian C. Stewart,et al.  Highly efficient ruthenium catalysts for the formation of tetrasubstituted olefins via ring-closing metathesis. , 2007, Organic letters.

[10]  Anatoly Chlenov,et al.  Ruthenium-catalyzed ring-closing metathesis to form tetrasubstituted olefins. , 2007, Organic letters.

[11]  H. Araki,et al.  Highly selective copper-catalyzed ring expansion of vinyl thiiranes: application to synthesis of biotin and the heterocyclic core of plavix. , 2007, Journal of the American Chemical Society.

[12]  J. T. Njardarson,et al.  Copper-catalyzed rearrangement of vinyl oxiranes. , 2006, Journal of the American Chemical Society.

[13]  I. G. Collado,et al.  Synthesis and free radical scavenging activity of a novel metabolite from the fungus Colletotrichum gloeosporioides. , 2006, Bioorganic & medicinal chemistry letters.

[14]  Ningyi Chen,et al.  Reaction of alpha-(N-carbamoyl)alkylcuprates with enantioenriched propargyl electrophiles: synthesis of enantioenriched 3-pyrrolines. , 2006, The Journal of organic chemistry.

[15]  N. Morita,et al.  Gold‐Catalyzed Cycloisomerization of α‐Aminoallenes to 3‐Pyrrolines –Optimization and Mechanistic Studies , 2006 .

[16]  L. Hegedus,et al.  Gold-Catalyzed and N-Iodosuccinimide-Mediated Cyclization of γ-Substituted Allenamides , 2006 .

[17]  H. Reissig,et al.  Efficient approach to the Azaspirane core of FR 901483. , 2006, Organic letters.

[18]  R. Rossi,et al.  Synthesis and Biological Activity of Pyrrole, Pyrroline and Pyrrolidine Derivatives with Two Aryl Groups on Adjacent Positions , 2006 .

[19]  A. Fürstner,et al.  Total syntheses of amphidinolide X and Y. , 2006, Journal of the American Chemical Society.

[20]  R. Sarpong,et al.  Ga(III)-catalyzed cycloisomerization strategy for the synthesis of icetexane diterpenoids: total synthesis of (+/-)-salviasperanol. , 2006, Organic letters.

[21]  N. Morita,et al.  The First Gold-Catalyzed CS Bond Formation: Cycloisomerization of α-Thioallenes to 2,5-Dihydrothiophenes† , 2006 .

[22]  J. Bats,et al.  Gold Catalysis: Evidence for the In‐situ Reduction of Gold(III) During the Cyclization of Allenyl Carbinols , 2006 .

[23]  B. Alcaide,et al.  Efficient entry to diversely functionalized spirocyclic oxindoles from isatins through carbonyl-addition/cyclization reaction sequences. , 2006, The Journal of organic chemistry.

[24]  P. Guiry,et al.  Synthesis of Dihydrofurans Substituted in the 2‐Position , 2005 .

[25]  R. Grubbs,et al.  Prevention of undesirable isomerization during olefin metathesis. , 2005, Journal of the American Chemical Society.

[26]  Fred Wudl,et al.  Light‐Emitting Polythiophenes , 2005 .

[27]  I. Coldham,et al.  Intramolecular dipolar cycloaddition reactions of azomethine ylides. , 2005, Chemical reviews.

[28]  Phil Ho Lee,et al.  The indium-mediated selective introduction of allenyl and propargyl groups at the C4-position of 2-azetidinones and the AuCl3-catalyzed cyclization of 4-allenyl-2-azetidinones. , 2005, Angewandte Chemie.

[29]  W. Xiao,et al.  Lewis acid assisted ring-closing metathesis of chiral diallylamines: an efficient approach to enantiopure pyrrolidine derivatives. , 2005, Organic letters.

[30]  A. Fürstner,et al.  Total synthesis of amphidinolide X. , 2004, Journal of the American Chemical Society.

[31]  Yukio Shimada,et al.  Photoreactions of β-aziridinylacrylonitriles and acrylates with alkenes: formation of head-to-head adducts and application to the preparation of pyrrolizidine alkaloid , 2004 .

[32]  N. Morita,et al.  Gold Catalysis in Organic Synthesis: Efficient Cycloisomerization of α-Aminoallenes to 3-Pyrrolines , 2004 .

[33]  B. Schmidt Ruthenium-catalyzed olefin metathesis double-bond isomerization sequence. , 2004, The Journal of organic chemistry.

[34]  J. Bäckvall,et al.  Enantiocontrolled Synthesis of 3-Pyrrolines from α-Amino Allenes , 2004 .

[35]  T. Donohoe,et al.  A concise total synthesis of (+/-)-1-epiaustraline. , 2004, Organic letters.

[36]  T. Donohoe,et al.  An Efficient Synthesis of Lactacystinβ-Lactone , 2004 .

[37]  T. Donohoe,et al.  An Efficient Synthesis of Lactacystin β‐Lactone , 2004 .

[38]  H. Kotsuki,et al.  Diels-Alder reaction of thiophene: dramatic effects of high-pressure/solvent-free conditions. , 2004, Angewandte Chemie.

[39]  P. Rutledge,et al.  Total synthesis of a novel 2-thiabicyclo[3.2.0]heptan-6-one analogue of penicillin N , 2003 .

[40]  F. Felpin,et al.  Recent Advances in the Total Synthesis of Piperidine and Pyrrolidine Natural Alkaloids with Ring‐Closing Metathesis as a Key Step , 2003 .

[41]  S. Nguyen,et al.  Catalytic, three-component assembly reaction for the synthesis of pyrrolidines. , 2003, Organic letters.

[42]  W. H. Pearson,et al.  Cycloadditions of nonstabilized 2-azaallyllithiums (2-azaallyl anions) and azomethine ylides with alkenes: [3+2] Approaches to pyrrolidines and application to alkaloid total synthesis , 2003 .

[43]  T. Donohoe,et al.  Flexibility in the partial reduction of 2,5-disubstituted pyrroles: application to the synthesis of DMDP. , 2003, Organic letters.

[44]  B. Schmidt An Olefin Metathesis/Double Bond Isomerization Sequence Catalyzed by an In Situ Generated Ruthenium Hydride Species , 2003 .

[45]  N. Sergeeva,et al.  Carbonyl-yne reactions of 3,3,3-trifluoropyruvates , 2003 .

[46]  S. Ma,et al.  Efficient preparation of highly optically active (S)-(-)-2,3-allenols and (R)-(+)-2,3-allenyl acetates by a clean novozym-435-catalyzed enzymatic separation of racemic 2,3-allenols. , 2002, Chemistry.

[47]  M. Snapper,et al.  New tandem catalysis: preparation of cyclic enol ethers through a ruthenium-catalyzed ring-closing metathesis-olefin isomerization sequence. , 2002, Journal of the American Chemical Society.

[48]  T. Donohoe,et al.  Preparation of (+)-nemorensic acid and approaches to nemorensine using the partial reduction of electron deficient furans , 2002 .

[49]  W. Shipe,et al.  A convergent synthesis of the tricyclic architecture of the guanacastepenes featuring a selective ring fragmentation. , 2002, Organic letters.

[50]  S. Nolan,et al.  Efficiency of a ruthenium catalyst in metathesis reactions of sulfur-containing compounds. , 2002, Organic letters.

[51]  S. Diver,et al.  Ethylene metathesis of sulfur-containing alkynes , 2002 .

[52]  Q. Yao Synthesis of cyclic sulfones by ring-closing metathesis. , 2002, Organic letters.

[53]  R. Dieter,et al.  Synthesis of 3-Pyrrolines, Annulated 3-Pyrrolines, and Pyrroles from α-Amino Allenes , 2001 .

[54]  James D White,et al.  Asymmetric synthesis of (+)-loline, a pyrrolizidine alkaloid from rye grass and tall fescue , 2001 .

[55]  N. Krause,et al.  Gold(III) Chloride Catalyzed Cyclization of α-Hydroxyallenes to 2,5-Dihydrofurans , 2001 .

[56]  Jae Chol Lee,et al.  Total synthesis of tropoloisoquinolines: imerubrine, isoimerubrine, and grandirubrine. , 2001, Journal of the American Chemical Society.

[57]  T. Donohoe,et al.  The synthesis of (+)-nemorensic acid , 2000 .

[58]  D. Mitchell,et al.  Synthesis of the necine base (−)-supinidine from (S)-glutamic acid , 2000 .

[59]  D. O'Hagan Pyrrole, pyrrolidine, pyridine, piperidine and tropane alkaloids (1998 to 1999) , 2000 .

[60]  R. Grubbs,et al.  Synthesis and activity of a new generation of ruthenium-based olefin metathesis catalysts coordinated with 1,3-dimesityl-4,5-dihydroimidazol-2-ylidene ligands. , 1999, Organic letters.

[61]  J. P. Harrity,et al.  A Recyclable Ru-Based Metathesis Catalyst , 1999 .

[62]  R. Schrock,et al.  Mo-Catalyzed Asymmetric Synthesis of Dihydrofurans. Catalytic Kinetic Resolution and Enantioselective Desymmetrization through Ring-Closing Metathesis , 1998 .

[63]  C. Mukai,et al.  Stereoselective Total Synthesis of (+/-)-Swainsonine Based on Endo Mode Cyclization. , 1998, The Journal of organic chemistry.

[64]  F. Lefebvre,et al.  Metathetical cyclization of dienes containing P, O, S or Si heteroatoms by a cyclometallated aryloxy-carbene of tungsten. Inhibition effects and steric constraints: A review , 1998 .

[65]  M. Kurosu,et al.  Total Synthesis of (±)-Batrachotoxinin A , 1998 .

[66]  K. Gothelf,et al.  Asymmetric 1,3-Dipolar Cycloaddition Reactions. , 1998, Chemical reviews.

[67]  M. Node,et al.  New asymmetric transformation of optically active allene-1,3-dicarboxylate and its application to the formal asymmetric synthesis of (–)-epibatidine , 1998 .

[68]  M. Elliott Saturated oxygen heterocycles , 2010 .

[69]  T. Thiemann,et al.  Lewis Acid Catalysis in the Oxidative Cycloaddition of Thiophenes(1). , 1997, The Journal of organic chemistry.

[70]  A. Padwa Tandem Processes of Metallo Carbenoids for the Synthesis of Azapolycycles , 1997 .

[71]  C. Kappe,et al.  Synthetic applications of furan Diels-Alder chemistry , 1997 .

[72]  R. Bradbury,et al.  β-Lactam-based azomethine ylide reactivity. Expedient synthesis of carbapenams and carbapenems , 1997 .

[73]  S. Blechert,et al.  A Flexible Synthesis of Azasugars and Homoazasugars via Olefin Metathesis , 1997 .

[74]  M. Trudell,et al.  A Short and Efficient Total Synthesis of (+/-)-Epibatidine. , 1996, The Journal of organic chemistry.

[75]  A. Padwa,et al.  Cascade Processes of Metallo Carbenoids. , 1996, Chemical reviews.

[76]  J. Cha,et al.  4 + 3 CYCLOADDITIONS OF CYCLIC OXYALLYLS AND CYCLIC 1,3-DIENES , 1995 .

[77]  G. Pandey,et al.  A short and new synthesis of optically pure (+)-retronecine , 1994 .

[78]  S. Nguyen,et al.  Catalytic ring-closing metathesis of functionalized dienes by a ruthenium carbene complex , 1993 .

[79]  J. Harmange,et al.  Synthetic routes to 2,5-disubstituted tetrahydrofurans , 1993 .

[80]  Z. Marcinow,et al.  The Birch Reduction of Aromatic Compounds , 1993 .

[81]  M. Leconte,et al.  Metathesis of sulfur-containing olefins with a metallacyclic aryloxo(chloro)neopentylidenetungsten complex , 1993 .

[82]  A. Padwa,et al.  Application of Intramolecular Carbenoid Reactions in Organic Synthesis , 1992 .

[83]  R. Grubbs,et al.  The synthesis of nitrogen heterocycles via catalytic ring-closing metathesis of dienes , 1992 .

[84]  A. Padwa Generation and Utilization of Carbonyl Ylides via the Tandem Cyclization-Cycloaddition Method , 2010 .

[85]  J. A. Marshall,et al.  Synthesis of enantioenriched .alpha.-hydroxy-.alpha.-allenylacetic acids by [2,3] Wittig rearrangement of .alpha.-(propargyloxy)acetates , 1991 .

[86]  G. Bazan,et al.  Living ring-opening metathesis polymerization of 2,3-difunctionalized 7-oxanorbornenes and 7-oxanorbornadienes by Mo(CHCMe2R)(NC6H3-iso-Pr2-2,6)(O-tert-Bu)2 and Mo(CHCMe2R)(NC6H3-iso-Pr2-2,6)(OCMe2CF3)2 , 1991 .

[87]  A. Padwa,et al.  Ylide formation from the reaction of carbenes and carbenoids with heteroatom lone pairs , 1991 .

[88]  D. A. Whiting,et al.  Synthetic studies on O-heterocycles via cycloadditions. Part 2. Adducts from styrene oxides , 1990 .

[89]  L. S. Liebeskind,et al.  Palladium Mediated Formation of Δ1- and Δ2-Carbapenems by Cyclofunctionalization of 4-Allenylazetidinones and 4-(2-Propynyl)azetidinones. , 1988 .

[90]  A. Schultz,et al.  2,4-Cyclohexadien-1-ones in organic synthesis. Further studies of molecular rearrangements occurring from products in intramolecular azide-olefin cycloadditions , 1987 .

[91]  M. Drew,et al.  High-pressure synthesis, structures, and conformational properties of some derivatives of 7-azabicyclo[2.2.1] heptane. X-Ray determination of endo-10-benzoyl-4-phenyl-4,10-diazatricyclo[5.2.1.0]dec-8-ene-3,5-dione and exo-10-acetyl-4-phenyl-4,10-diazatricyclo[5.2.1.0]decane-3,5-dione , 1985 .

[92]  Y. Morizawa,et al.  Pd(O) promoted transformation of N-tosyl-2-(1,3-butadienyl)-aziridine into N-tosyl-2-vinyl-3-pyrroline , 1985 .

[93]  A. Bridges,et al.  A simple, versatile preparation of highly substituted 2,5-dihydro-oxoles , 1984 .

[94]  W. Eberbach,et al.  Zur Reaktivität geometrisch fixierter Vinylaziridine: Synthese und Thermolyse einiger 3,4-Epiminocyclohexene , 1983 .

[95]  R. Huisgen,et al.  New thiocarbonyl ylides from thiobenzophenone , 1983 .

[96]  S. Hall,et al.  An efficient stereospecific total synthesis of (.+-.)-anisomycin and related new synthetic antibiotics , 1982 .

[97]  R. Huisgen,et al.  Three-component reactions of diazomalonic ester, benzaldehyde, and electrophilic olefins , 1982 .

[98]  S. Weinreb,et al.  Synthesis of indolizidine alkaloids via the intramolecular imino Diels-Alder reaction , 1981 .

[99]  W. Eberbach,et al.  Carbonyl‐Ylide als Cycloadditionspartner: Intramolekularer Transfer einer ADM‐Einheit , 1981 .

[100]  P. Beaulieu,et al.  The synthesis of 2,5-dihydrofurans from α-allenic alcohols , 1980 .

[101]  K. Lempert,et al.  Allenes and Acetylenes. XVIII. Synthesis of 3-Pyrrolines by Silver(I)-catalyzed Cyclization of Allenic Amines. , 1979 .

[102]  R. Noyori,et al.  Carbon-carbon bond formation promoted by transition metal carbonyls. 17. Reactions of polybromo ketones with 1,3-dienes in the presence of iron carbonyls. New 3 + 4 .fwdarw. 7 cyclocoupling reaction forming 4-cycloheptenones , 1978 .

[103]  R. Huisgen Elektrocyclische Ringöffnungen von Ethylenoxiden , 1977 .

[104]  A. Padwa Intramolekulare 1,3‐dipolare Cycloadditionsreaktionen , 1976 .

[105]  K. Schaumburg,et al.  Diels-Alder Reactions of Thiophene Oxides Generated in situ. , 1976 .

[106]  J. Mcintosh,et al.  Dihydrothiophenes. II. Preparation and properties of some alkylated 2,5-dihydrothiophenes , 1974 .

[107]  F. Toda,et al.  Reactions of 1,1,4,4-tetraphenyl-3-bromobuta-1,2-diene-4-ol with mercuric acetate , 1969 .

[108]  E. Schweizer,et al.  Reactions of phosphorus compounds. XIV. General synthesis of 2,5-dihydrofurans , 1968 .

[109]  Edward E. Scheweizer Reactions of Phosphorus Compounds. III. A New General Ring Synthesis from Vinyltriphenylphosphonium Bromide , 1964 .