Chemodivergent Transformations of Alkynyl Imines

Anna W. Sromek; Arnold L. Rheingold; Donald J. Wink; Vladimir Gevorgyan

doi:10.1055/s-2006-949652

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Chemodivergent Transformations of Alkynyl Imines

Anna W. Sromek^a, Arnold L. Rheingold^b, Donald J. Wink^a, Vladimir Gevorgyan*^a
^a University of Illinois at Chicago, Department of Chemistry, 845 W. Taylor St., room 4500 SES, m/c 111, Chicago, IL 60607, USA
^b University of California at San Diego, Department of Chemistry and Biochemistry, 9500 Gilman Drive, m/c 0358, La Jolla, CA 92093, USA
Fax: +1(312)3550836; e-Mail: vlad@uic.edu;

Abstract

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Abstract

The investigation of cycloisomerization cascades of alkynyl imines towards pyrroles unexpectedly led to the development of chemodivergent routes towards quinolines and fused pyrrolines. It was found that, depending on the nature of the nitrogen substituent and choice of reagents, up to three different heterocyclic cores can be accessed from a common structural precursor.

Key words

alkynyl imines - cycloaddition - electrophilic cyclization - heterocycles - quinoline

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References

References and Notes

For recent examples, see:

<A NAME="RY00306ST-1A">1a</A> Pandey S. Takashima W. Kaneto K. React. Funct. Polym. 2004, 58: 103

<A NAME="RY00306ST-1B">1b</A> Georgiadis R. Peterlinz KA. Rahn JR. Peterson AW. Grassi JH. Langmuir 2000, 16: 6759

<A NAME="RY00306ST-1C">1c</A> Czerwinski W. Wrzeszcz G. Kania K. Rabek JF. Linden LA. J. Mater. Sci. 2000, 35: 2305

For recent reviews on heterocycle synthesis, see:

<A NAME="RY00306ST-2A">2a</A> Nakamura I. Yamamoto Y. Chem. Rev. 2004, 104: 2127

<A NAME="RY00306ST-2B">2b</A> Zeni G. Larock RC. Chem. Rev. 2004, 104: 2285

<A NAME="RY00306ST-2C">2c</A> Alonso F. Beletskaya IP. Yus M. Chem. Rev. 2004, 104: 3079

<A NAME="RY00306ST-2D">2d</A> Black DStC. In Science of Synthesis 5th Ed., Vol. 9: Maas G. Thieme; Stuttgart: 2000. p.543-552

<A NAME="RY00306ST-3">3</A> Kel’in AV. Sromek AW. Gevorgyan V. J. Am. Chem. Soc. 2001, 123: 2074

<A NAME="RY00306ST-4">4</A> Kel’in AV. Gevorgyan V. J. Org. Chem. 2002, 67: 95

<A NAME="RY00306ST-5">5</A> Sromek AW. Rubina M. Gevorgyan V. J. Am. Chem. Soc. 2005, 127: 10500

<A NAME="RY00306ST-6">6</A> Kim JT. Kel’in AV. Gevorgyan V. Angew. Chem. Int. Ed. 2003, 42: 98

<A NAME="RY00306ST-7">7</A> Sromek AW. Kel’in AV. Gevorgyan V. Angew. Chem. Int. Ed. 2004, 43: 2280

<A NAME="RY00306ST-8">8</A> Lin S. Sheng H. Huang Y. Synthesis 1991, 235

<A NAME="RY00306ST-9A">9a</A> Ried W. Winkler H. Chem. Ber. 1979, 112: 384

<A NAME="RY00306ST-9B">9b</A> Ried W. Weidemann P. Chem. Ber. 1971, 104: 3329

<A NAME="RY00306ST-9C">9c</A> Himbert G. Schwickerath W. Liebigs Ann. Chem. 1984, 85

<A NAME="RY00306ST-10">10</A> Strained cyclic cumulenes have been proposed as intermediates in benzannulation reactions, see: Danheiser RL. Gould AE. Fernández de la Pradilla RF. Helgason AL. J. Org. Chem. 1994, 59: 5514

For recent reports of transition-metal-catalyzed cyclization of alkynyl imines into quinolines, see:

<A NAME="RY00306ST-11A">11a</A> Movassaghi M. Hill MD. J. Am. Chem. Soc. 2006, 128: 4592

<A NAME="RY00306ST-11B">11b</A> Sangu K. Fuchibe K. Akiyama T. Org. Lett. 2004, 6: 353

CCDC-605793 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge at www.ccdc.cam.uk/conts/retrieving.html [or from the Cambridge Crystallographic Data Center, 12 Union Road, Cambridge, CB2 1EZ, UK; fax: +44(1223)336033; email: deposit@ccdc.cam.ac.uk].

A base-assisted formal [1,3]-H shift in alkynyl imines 1 into allenyl imines has been proposed as the first step of the cycloisomerization cascade towards pyrroles 2; see ref. 3 for a detailed discussion.

For selected examples of metal-catalyzed [2+2]-cyclo-additions, see:

<A NAME="RY00306ST-14A">14a</A> Mango FD. Schachtschneider JH. J. Am. Chem. Soc. 1971, 93: 1123

<A NAME="RY00306ST-14B">14b</A> Fraser AR. Bird PH. Bezman SA. Shapley JR. White R. Osborn JA. J. Am. Chem. Soc. 1973, 95: 597

<A NAME="RY00306ST-14C">14c</A> Baik T.-G. Luis AL. Wang LC. Krische MJ. J. Am. Chem. Soc. 2001, 123: 6716

For the thermal cyclization of allenyl thioimine into bicyclic pyrroline derivatives, see:

<A NAME="RY00306ST-15A">15a</A> Brandsma L. Nedolya NA. Heerma V. Van der Kerk ASHTM. Lutz ETHG. de Lang R.-J. Afonin AV. Trofimov BA. Chem. Heterocycl. Compd. (Engl. Transl.) 1997, 33: 493

<A NAME="RY00306ST-15B">15b</A> Brandsma L. Nedolya NA. Verkruijsse HD. Owen NL. Li D. Trofimov BA. Tetrahedron Lett. 1997, 38: 6905

<A NAME="RY00306ST-15C">15c</A> Trofimov BA. Nedolya NA. Brandsma L. Frolov YuL. Larionova EYu. Toryashinova DD. Kobychev VB. Vitkovskaya NM. Sulfur Lett. 1999, 22: 249

Quinolines 3; General Procedure. A 3-mL Wheaton microreactor equipped with a Teflon spin vane and Mininert valve under an argon atmosphere was employed. CuI (23 mg, 0.12 mmol), anhyd DMA (1.80 mL), Et₃N·HCl (55 mg, 0.40 mmol), and alkynyl imine 1 (88 mg, 0.40 mmol) were added successively. The microreactor was then placed in an aluminum block, which was preheated to 110 °C. The mixture was stirred at 110 °C with protection from light for 24 h. The progress of the reaction was monitored by GC-MS. When the reaction was complete the mixture was cooled to r.t. and poured into H₂O (15 mL). After shaking with hexanes-Et₂O (1:1, 5 mL) a three-layer system usually formed. The lower(aqueous) phase and upper(organic) phase were thoroughly separated from the middle layer, which contained an emulsion of Cu⁺ complexes. The emulsion and water phases were separately extracted with hexanes-Et₂O (1:1; 3 × 2 mL and 1 × 2 mL, respectively). The combined extracts were dried over anhyd Na₂CO₃, the solvent was evaporated under reduced pressure, and the residue was purified over a short column of silica gel(benzene) to afford 2-phenyl-4-methylquinoline 3 in 93% isolated yield.
Fused Pyrrolines 4; General Procedure. A 3-mL Wheaton microreactor equipped with a Teflon spin vane and Mininert valve under an argon atmosphere was employed. CuI (23 mg, 0.12 mmol), anhyd DMA (1.80 mL), and imine 1 (0.40 mmol) were added successively. After the CuI had dissolved, anhyd Et₃N (0.25 mL) was added, and the microreactor was placed in an aluminum heating block, preheated to 110 °C. The mixture was stirred at 110 °C with protection from light. The reaction was monitored by GC-MS. When the reaction was complete, the mixture was cooled to r.t., and poured into H₂O (15 mL). After shaking with hexanes (5 mL) a three-layer system usually formed. The lower(aqueous) phase and upper(organic) phase were thoroughly separated from the middle layer, which contained an emulsion of Cu⁺ complexes. The emulsion and water phases were separately extracted with hexanes (3 × 2 mL and 1 × 2 mL, respectively). The combined hexanes extracts were dried over anhyd Na₂CO₃, the solvent was evaporated under reduced pressure, and the residue was purified over a short column of silica gel (hexanes or hexanes-EtOAc) to afford the pure fused pyrroline 4.