Download PDF
Synlett 2008(19): 2913-2937  
DOI: 10.1055/s-0028-1087339
ACCOUNT
© Georg Thieme Verlag Stuttgart ˙ New York

Stereoselective Synthesis of Saturated Heterocycles via Palladium-Catalyzed Alkene Carboetherification and Carboamination Reactions

John P. Wolfe*
Department of Chemistry, University of Michigan, 930 N. University Avenue, Ann Arbor, MI 48109-1055, USA
Fax: +1(734)6153790; e-Mail: jpwolfe@umich.edu;
Further Information

Publication History

Received 9 June 2008
Publication Date:
12 November 2008 (online)

    Permissions and Reprints All articles of this category

Abstract

The development of palladium-catalyzed carboetherification and carboamination reactions between aryl or alkenyl halides and alkenes bearing pendant heteroatoms is described. These transformations effect the stereoselective construction of useful heterocycles, such as tetrahydrofurans, pyrrolidines, imidazolidin-2-ones, isoxazolidines, and piperazines. The scope, limitations, and applications of these reactions are presented, and current stereochemical models are described. The mechanism of the product formation, which involves an unusual intramolecular syn-insertion of an alkene into a palladium-heteroatom bond, is also discussed in detail.

1 Introduction

2 Palladium-Catalyzed Synthesis of Tetrahydrofurans from γ-Hydroxyalkenes and Aryl or Alkenyl Halides

2.1 Mechanism of the Tetrahydrofuran Formation

3 Palladium-Catalyzed Synthesis of Pyrrolidines from γ-Aminoalkenes and Aryl or Alkenyl Halides

3.1 Tandem Palladium-Catalyzed N-Arylation-Carboamination Reactions of Primary Amines

3.2 Palladium-Catalyzed Carboamination Reactions of N-Protected γ-Aminoalkenes

3.3 Mechanism of the Palladium-Catalyzed Carboamination Reactions: Surprises and Utility

3.4 Application of the Palladium-Catalyzed Carboamination of N-Protected γ-Aminoalkenes to the Stereoselective Synthesis of (+)-Preussin and Its Analogues

4 Synthesis of Imidazolidin-2-ones via Palladium-Catalyzed Carboamination Reactions

5 Synthesis of Isoxazolidines via Palladium-Catalyzed Carboetherification Reactions

6 Synthesis of Piperazines via Palladium-Catalyzed Carboamination Reactions

7 Summary and Future Outlook

Key words

alkenes - catalysis - heterocycles - palladium - stereoselective synthesis

    References

  • For reviews on biologically active tetrahydrofurans and pyrrolidines, see:
  • 1a Kang EJ. Lee E. Chem. Rev.  2005,  105:  4348 
    Google Scholar
  • 1b Saleem M. Kim HJ. Ali MS. Lee YS. Nat. Prod. Rep.  2005,  22:  696 
    Google Scholar
  • 1c Bermejo A. Figadere B. Zafra-Polo M.-C. Barrachina I. Estornell E. Cortes D. Nat. Prod. Rep.  2005,  22:  269 
    Google Scholar
  • 1d Daly JW. Spande TF. Garraffo HM. J. Nat. Prod.  2005,  68:  1556 
    Google Scholar
  • 1e Hackling AE. Stark H. ChemBioChem  2002,  3:  946 
    Google Scholar
  • 1f Lewis JR. Nat. Prod. Rep.  2001,  18:  95 
    Google Scholar
  • For recent select reviews on metal-catalyzed or -mediated reactions for the synthesis of heterocycles, see:
  • 2a D’Souza DM. Mueller TJJ. Chem. Soc. Rev.  2007,  36:  1095 
    Google Scholar
  • 2b Chemler SR. Fuller PH. Chem. Soc. Rev.  2007,  36:  1153 
    Google Scholar
  • 2c Minatti A. Muniz K. Chem. Soc. Rev.  2007,  36:  1142 
    Google Scholar
  • 2d Zeni G. Larock RC. Chem. Rev.  2006,  106:  4644 
    Google Scholar
  • 2e Conreaux D. Bouyssi D. Monteiro N. Balme G. Curr. Org. Chem.  2006,  10:  1325 
    Google Scholar
  • 2f Muzart J. Tetrahedron  2005,  61:  5955 
    Google Scholar
  • 2g Wolfe JP. Thomas JS. Curr. Org. Chem.  2005,  9:  625 
    Google Scholar
  • 2h Nakamura I. Yamamoto Y. Chem. Rev.  2004,  104:  2127 
    Google Scholar
  • 2i Zeni G. Larock RC. Chem. Rev.  2004,  104:  2285 
    Google Scholar
  • 2j Deiters A. Martin SF. Chem. Rev.  2004,  104:  2199 
    Google Scholar
  • 2k Barluenga J. Santamaria J. Tomas M. Chem. Rev.  2004,  104:  2259 
    Google Scholar
  • 2l McReynolds MD. Dougherty JM. Hanson PR. Chem. Rev.  2004,  104:  2239 
    Google Scholar
  • For reviews on the synthesis of tetrahydrofurans, see:
  • 3a Wolfe JP. Hay MB. Tetrahedron  2007,  63:  261 
    Google Scholar
  • 3b Miura K. Hosomi A. Synlett  2003,  143 
    Google Scholar
  • 3c Koert U. Synthesis  1995,  115 
    Google Scholar
  • 3d Harmange J.-C. Figadere B. Tetrahedron: Asymmetry  1993,  4:  1711 
    Google Scholar
  • 3e Cardillo G. Orena M. Tetrahedron  1990,  46:  3321 
    Google Scholar
  • 3f Boivin TLB. Tetrahedron  1987,  43:  3309 
    Google Scholar
  • For reviews on the synthesis of pyrrolidines, see:
  • 4a Bellina F. Rossi R. Tetrahedron  2006,  62:  7213 
    Google Scholar
  • 4b Coldham I. Hufton R. Chem. Rev.  2005,  105:  2765 
    Google Scholar
  • 4c Pyne SG. Davis AS. Gates NJ. Hartley JP. Lindsay KB. Machan T. Tang M. Synlett  2004,  2670 
    Google Scholar
  • 4d Felpin F.-X. Lebreton J. Eur. J. Org. Chem.  2003,  3693 
    Google Scholar
  • For related transformations of γ-hydroxy- or γ-amino-substituted allenes or alkynes, see:
  • 5a Balme G. Bouyssi D. Lomberget T. Monteiro N. Synthesis  2003,  2115 
    Google Scholar
  • 5b Kang S.-K. Baik T.-G. Kulak AN. Synlett  1999,  324 
    Google Scholar
  • 5c Jacobi PA. Liu H. Org. Lett.  1999,  1:  341 
    Google Scholar
  • 5d Walkup RD. Guan L. Mosher MD. Kim SW. Kim YS. Synlett  1993,  88 
    Google Scholar
  • 5e Luo FT. Schreuder I. Wang RT. J. Org. Chem.  1992,  57:  2213 
    Google Scholar
  • 5f Luo FT. Wang RT. Tetrahedron Lett.  1992,  33:  6835 
    Google Scholar
  • 5g Arcadi A. Cacchi S. Marinelli F. Tetrahedron Lett.  1992,  33:  3915 
    Google Scholar
  • 5h Davies IW. Scopes DIC. Gallagher T. Synlett  1993,  85 
    Google Scholar
  • 5i Wolf LB. Tjen KCMF. Rutjes FPJT. Hiemstra H. Schoemaker HE. Tetrahedron Lett.  1998,  39:  5081 
    Google Scholar
  • Other metal-catalyzed or -mediated reactions of γ-hydroxy- or γ-aminoalkenes that generate heterocycles with the formation of both a carbon-heteroatom and a carbon-carbon bond have also been reported. For examples of copper-catalyzed intramolecular carboamination reactions of 2-allyl-N-(arylsulfonyl)anilines and related derivatives, see:
  • 6a Sherman ES. Fuller PH. Kasi D. Chemler SR.
    J. Org. Chem.  2007,  72:  3896 
    Google Scholar
  • 6b Sherman ES. Chemler SR. Tan TB. Gerlits O. Org. Lett.  2004,  6:  1573 
    Google Scholar
  • For Pd(II)-catalyzed aminocarbonylation reactions of alkenes bearing tethered nitrogen nucleophiles, see:
  • 6c Harayama H. Abe A. Sakado T. Kimura M. Fugami K. Tanaka S. Tamaru Y. J. Org. Chem.  1997,  62:  2113 
    Google Scholar
  • For carboamination reactions between alkenes and N-allylsulfonamides, see:
  • 6d Scarborough CC. Stahl SS. Org. Lett.  2006,  8:  3251 
    Google Scholar
  • For carboamination reactions of vinylcyclopropanes, see:
  • 6e Larock RC. Yum EK. Synlett  1990,  529 
    Google Scholar
  • For Pd(II)-catalyzed alkoxycarbonylation reactions of alkenes bearing tethered oxygen nucleophiles, see:
  • 6f Semmelhack MF. Bodurow C. J. Am. Chem. Soc.  1984,  106:  1496 
    Google Scholar
  • 6g Semmelhack MF. Zhang N. J. Org. Chem.  1989,  54:  4483 
    Google Scholar
  • 6h McCormick M. Monahan R. Soria J. Goldsmith D. Liotta D. J. Org. Chem.  1989,  54:  4485 
    Google Scholar
  • 6i Semmelhack MF. Kim C. Zhang N. Bodurow C. Sanner M. Dobler W. Meier M. Pure Appl. Chem.  1990,  62:  2035 ; and references cited therein
    Google Scholar
  • For Pd-catalyzed reactions of β-aminoalkenes with alkenyl halides which afford pyrrolidine products via formal 1,1-addition to the alkene, see:
  • 7a Harris GD. Herr RJ. Weinreb SM. J. Org. Chem.  1992,  57:  2528 
    Google Scholar
  • 7b Harris GD. Herr RJ. Weinreb SM. J. Org. Chem.  1993,  58:  5452 
    Google Scholar
  • 7c Larock RC. Yang H. Weinreb SM. Herr RJ. J. Org. Chem.  1994,  59:  4172 
    Google Scholar
  • 8 For a review on Pd(0)- and Pd(II)-catalyzed carboetherification and carboamination reactions, see: Wolfe JP. Eur. J. Org. Chem.  2007,  571 
    CrossrefGoogle Scholar
  • 9 Crabtree RH. The Organometallic Chemistry of the Transition Metals   4th ed.:  John Wiley and Sons; Hoboken NJ: 2005. 
    Google Scholar
  • 10a Yamamoto A. J. Chem. Soc., Dalton Trans.  1999,  1027 
    Google Scholar
  • 10b Beletskaya IP. Cheprakov AV. Chem. Rev.  2000,  100:  3009 
    Google Scholar
  • 11a Lin BL. Clough CR. Hillhouse GL. J. Am. Chem. Soc.  2002,  124:  2890 
    Google Scholar
  • 11b Koo K. Hillhouse GL. Organometallics  1995,  14:  4421 
    Google Scholar
  • 11c Matsunaga PT. Hillhouse GL. Rheingold AL. J. Am. Chem. Soc.  1993,  115:  2075 
    Google Scholar
  • 11d Koo K. Hillhouse GL. Organometallics  1998,  17:  2924 
    Google Scholar
  • 11e Williams BS. Goldberg KI. J. Am. Chem. Soc.  2001,  123:  2576 
    Google Scholar
  • 11f Brice JL. Harang JE. Timokhin VI. Anastasi NR. Stahl SS. J. Am. Chem. Soc.  2005,  127:  2868 
    Google Scholar
  • 11g Dick AR. Kampf JW. Sanford MS. J. Am. Chem. Soc.  2005,  127:  12790 
    Google Scholar
  • 12a Hosokawa T. Murahashi S.-I. Acc. Chem. Res.  1990,  23:  49 
    Google Scholar
  • 12b Hegedus LS. Angew. Chem., Int. Ed. Engl.  1988,  27:  1113 
    Google Scholar
  • 13a Muci AR. Buchwald SL. Top. Curr. Chem.  2002,  219:  131 
    Google Scholar
  • 13b Hartwig JF. Pure Appl. Chem.  1999,  71:  1417 
    Google Scholar
  • 14a Villanueva LA. Abboud KA. Boncella JM. Organometallics  1992,  11:  2963 
    Google Scholar
  • 14b VanderLende DD. Abboud KA. Boncella JM. Inorg. Chem.  1995,  34:  5319 
    Google Scholar
  • 14c Cowan RL. Trogler WC. J. Am. Chem. Soc.  1989,  111:  4750 
    Google Scholar
  • 14d Bryndza HE. Organometallics  1985,  4:  406 ; and references cited therein
    Google Scholar
  • 14e Bennett MA. Jin H. Li S. Rendina LM. Willis AC. J. Am. Chem. Soc.  1995,  117:  8335 
    Google Scholar
  • 14f Ritter JCM. Bergman RG. J. Am. Chem. Soc.  1997,  119:  2580 
    Google Scholar
  • 14g Casalnuovo AL. Calabrese JC. Milstein D. J. Am. Chem. Soc.  1988,  110:  6738 
    Google Scholar
  • 14h Hamed O. Thompson C. Henry PM. J. Org. Chem.  1997,  62:  7082 
    Google Scholar
  • 14i Nelson DJ. Li R. Brammer C. J. Am. Chem. Soc.  2001,  123:  1564 
    Google Scholar
  • For recent studies on alkene insertion into late transition metal-oxygen or -nitrogen bonds, see:
  • 15a

    See also ref. 11f

    Google Scholar
  • 15b Hayashi T. Yamasaki K. Mimura M. Uozumi Y.
    J. Am. Chem. Soc.  2004,  126:  3036 
    Google Scholar
  • 15c Zhao P. Krug C. Hartwig JF. J. Am. Chem. Soc.  2005,  127:  12066 
    Google Scholar
  • 15d Trend RM. Ramtohul YK. Stoltz BM. J. Am. Chem. Soc.  2005,  127:  17778 
    Google Scholar
  • 15e Zhao P. Incarvito CD. Hartwig JF. J. Am. Chem. Soc.  2006,  128:  9642 
    Google Scholar
  • 16 Milstein D. Stille JK. J. Am. Chem. Soc.  1979,  101:  4981 
    CrossrefGoogle Scholar
  • 17 Larock RC. Leung W.-Y. Stoltz-Dunn S. Tetrahedron Lett.  1989,  30:  6629 
    CrossrefGoogle Scholar
  • 18 Fournet G. Balme G. Gore J. Tetrahedron  1990,  46:  7763 
    CrossrefGoogle Scholar
  • 19 Trost BM. Pfrengle W. Urabe H. Dumas J. J. Am. Chem. Soc.  1992,  114:  1923 
    CrossrefGoogle Scholar
  • 20a Wolfe JP. Rossi MA. J. Am. Chem. Soc.  2004,  126:  1620 
    Google Scholar
  • 20b Hay MB. Hardin AR. Wolfe JP. J. Org. Chem.  2005,  70:  3099 
    Google Scholar
  • 22a Widenhoefer RA. Zhong HA. Buchwald SL. J. Am. Chem. Soc.  1997,  119:  6787 
    Google Scholar
  • 22b Widenhoefer RA. Buchwald SL. J. Am. Chem. Soc.  1998,  120:  6504 
    Google Scholar
  • 22c Mann G. Hartwig JF. J. Am. Chem. Soc.  1996,  118:  13109 
    Google Scholar
  • 24a Hay MB. Wolfe JP. J. Am. Chem. Soc.  2005,  127:  16468 
    Google Scholar
  • 24b Hay MB. Wolfe JP. Tetrahedron Lett.  2006,  47:  2793 
    Google Scholar
  • 25 Yeh has recently described related carboetherification reactions of dienes, see: Yeh M.-CP. Tsao W.-C. Tu L.-H. Organometallics  2005,  24:  5909 
    CrossrefGoogle Scholar
  • The insertion of alkenes into palladium-carbon bonds is not reversible in systems where the alkylpalladium intermediate generated by carbopalladation contains syn-β-hydrogen atoms, as β-hydride elimination is generally faster than β-aryl or β-alkyl elimination. For rare examples of β-aryl and β-alkyl elimination from Pd(II) complexes that lack β-hydrogen atoms, see:
  • 26a Campora J. Gutierrez-Puebla E. Lopez JA. Monge A. Palma P. del Rio D. Carmona E. Angew. Chem. Int. Ed.  2001,  40:  3641 
    Google Scholar
  • 26b Catellani M. Frignani F. Rangoni A. Angew. Chem., Int. Ed. Engl.  1997,  36:  119 
    Google Scholar
  • 26c Catellani M. Fagnola MC. Angew. Chem., Int. Ed. Engl.  1994,  33:  2421 
    Google Scholar
  • 26d Matsumura S. Maeda Y. Nishimura T. Uemura S. J. Am. Chem. Soc.  2003,  125:  8862 
    Google Scholar
  • 26e Wang X. Stankovich SZ. Widenhoefer RA. Organometallics  2002,  21:  901 ; and references cited therein
    Google Scholar
  • 27 For an example of stereochemical inversion in an isolated palladium complex that proceeds through a similar mechanism, see: Burke BJ. Overman LE. J. Am. Chem. Soc.  2004,  126:  16820 
    CrossrefGoogle Scholar
  • For related examples of stereospecific deuterium migration via reversible β-hydride/deuteride elimination processes, see:
  • 29a Qian H. Widenhoefer RA. J. Am. Chem. Soc.  2003,  125:  2056 
    Google Scholar
  • 29b

    See also ref. 15b

    Google Scholar
  • 29c

    See also ref. 15d

    Google Scholar
  • 30a Ney JE. Wolfe JP. Angew. Chem. Int. Ed.  2004,  43:  3605 
    Google Scholar
  • 30b Ney JE. Hay MB. Yang Q. Wolfe JP. Adv. Synth. Catal.  2005,  347:  1614 
    Google Scholar
  • 32a Lira R. Wolfe JP. J. Am. Chem. Soc.  2004,  126:  13906 
    Google Scholar
  • 32b Yang Q. Ney JE. Wolfe JP. Org. Lett.  2005,  7:  2575 
    Google Scholar
  • 33a Saito S. Hatanaka K. Yamamoto H. Org. Lett.  2000,  2:  1891 
    Google Scholar
  • 33b Overman LE. Owen CE. Pavan MM. Richards CJ. Org. Lett.  2003,  5:  1809 
    Google Scholar
  • 33c Taniyama D. Hasegawa M. Tomioka K. Tetrahedron: Asymmetry  1999,  10:  221 
    Google Scholar
  • 34a Bordwell FG. Algrim DJ. J. Am. Chem. Soc.  1988,  110:  2964 
    Google Scholar
  • 34b Bordwell FG. Ji G.-Z. J. Am. Chem. Soc.  1991,  113:  8398 
    Google Scholar
  • 34c Zhang X.-M. Bordwell FG. J. Org. Chem.  1994,  59:  6456 
    Google Scholar
  • 35a Bertrand MB. Wolfe JP. Tetrahedron  2005,  61:  6447 
    Google Scholar
  • 35b Bertrand MB. Leathen ML. Wolfe JP. Org. Lett.  2007,  9:  457 
    Google Scholar
  • 36 Tom NJ. Simon WM. Frost HN. Ewing M. Tetrahedron Lett.  2004,  45:  905 
    CrossrefGoogle Scholar
  • 38 Bertrand MB. Wolfe JP. Org. Lett.  2007,  9:  3073 
    CrossrefGoogle Scholar
  • For Pd-catalyzed reactions of aryl bromides with norbornene and related bicyclo[2.2.n]alkenes which afford benzocyclobutene products, see:
  • 39a Catellani M. Chiusoli GP. Ricotti S. J. Organomet. Chem.  1985,  296:  C11 
    Google Scholar
  • 39b Catellani M. Chiusoli GP. Ricotti S. Sabini F. Gazz. Chim. Ital.  1985,  115:  685 
    Google Scholar
  • 39c Catellani M. Ferioli L. Synthesis  1996,  769 
    Google Scholar
  • 40 Ney JE. Wolfe JP. J. Am. Chem. Soc.  2005,  127:  8644 
    CrossrefGoogle Scholar
  • For a discussion of the kinetic and thermodynamic effects in palladium amido complex formation, see:
  • 41a Meyers C. Maes BUW. Loones KTJ. Bal G. Lemiere GLF. Dommisse RA. J. Org. Chem.  2004,  69:  6010 
    Google Scholar
  • 41b Driver MS. Hartwig JF. Organometallics  1997,  16:  5706 
    Google Scholar
  • 42 When NaOt-Bu was employed as the base with N-Boc- or N-acyl-protected substrates, the amido complex could also be generated via the reaction of 58 with the deprotonated carbamate or amide. In addition, the amido complex could also be generated through the reaction of the amine, carbamate, or amide with an LnPd(Ar)(Ot-Bu) complex, see: Shekhar S. Hartwig JF. Organometallics  2007,  26:  340 
    CrossrefGoogle Scholar
  • β-Heteroatom elimination from Pd complexes has been previously observed. Thus, it is likely that the syn-oxypalladation and syn-aminopalladation reactions described in this article are reversible, see:
  • 43a Hacksell U. Daves GD. Organometallics  1983,  2:  772 
    Google Scholar
  • 43b Zhu G. Lu X. Organometallics  1995,  14:  4899 
    Google Scholar
  • 43c Zhao H. Ariafard A. Lin Z. Organometallics  2006,  25:  812 ; and references cited therein
    Google Scholar
  • For early examples, see:
  • 44a Kasahara A. Izumi T. Takeda T. Imamura H. Bull. Chem. Soc. Jpn.  1974,  47:  183 
    Google Scholar
  • 44b Andersson C.-M. Larsson J. Hallberg A. J. Org. Chem.  1990,  55:  5757 
    Google Scholar
  • For a recent review, see:
  • 44c Oestreich M. Eur. J. Org. Chem.  2005,  783 
    Google Scholar
  • For recent reviews, see:
  • 45a Campeau L.-C. Fagnou K. Chem. Commun.  2006,  1253 
    Google Scholar
  • 45b Catellani M. Synlett  2003,  298 
    Google Scholar
  • 46a Zhang L. Zetterberg K. Organometallics  1991,  10:  3806 
    Google Scholar
  • 46b Oestreich M. Dennison PR. Kodanko JJ. Overman LE. Angew. Chem. Int. Ed.  2001,  40:  1439 
    Google Scholar
  • 46c Clique B. Fabritius C.-H. Couturier C. Monteiro N. Balme G. Chem. Commun.  2003,  272 
    Google Scholar
  • 47 Lee C.-W. Oh KS. Kim KS. Ahn KH. Org. Lett.  2000,  2:  1213 
    Google Scholar
  • 48a Gillie A. Stille JK. J. Am. Chem. Soc.  1980,  102:  4933 
    Google Scholar
  • 48b Driver MS. Hartwig JF. J. Am. Chem. Soc.  1997,  119:  8232 
    Google Scholar
  • 48c Driver MS. Hartwig JF. J. Am. Chem. Soc.  1996,  118:  7217 
    Google Scholar
  • 48d Culkin DA. Hartwig JF. Organometallics  2004,  23:  3398 ; and references cited therein
    Google Scholar
  • 48e van Leeuwen PWNM. Kamer PCJ. Reek JNH. Dierkes P. Chem. Rev.  2000,  100:  2741 
    Google Scholar
  • 48f Christmann U. Vilar R. Angew. Chem. Int. Ed.  2005,  44:  366 
    Google Scholar
  • 48g Brown JM. Cooley NA. Chem. Rev.  1988,  88:  1031 
    Google Scholar
  • 49a Jensen DR. Schultz MJ. Mueller JA. Sigman MS. Angew. Chem. Int. Ed.  2003,  42:  3810 
    Google Scholar
  • 49b Steinhoff BA. Stahl SS. Org. Lett.  2002,  4:  4179 ; and references cited therein
    Google Scholar
  • Ligand substitution reactions of d8-Pd(II) complexes generally occur via an associative mechanism, see:
  • 50a

    See also ref. 29a

    Google Scholar
  • 50b Shultz LH. Tempel DJ. Brookhart M. J. Am. Chem. Soc.  2001,  123:  11539 ; and references cited therein. For rare exceptions, see:
    Google Scholar
  • 50c Bartolome C. Espinet P. Martin-Alvarez JM. Villafane F. Eur. J. Inorg. Chem.  2004,  2326 
    Google Scholar
  • 50d Louie J. Hartwig JF. J. Am. Chem. Soc.  1995,  117:  11598 
    Google Scholar
  • 51 For the isolation of this compound, see: Schwartz RE. Liesch J. Hensens O. Zitano L. Honeycutt S. Garrity G. Fromtling RA. Onishi J. Monaghan R. J. Antibiot.  1988,  41:  1774 
    Google Scholar
  • 52a Johnson JH. Phillipson DW. Kahle AD.
    J. Antibiot.  1989,  42:  1184 
    Google Scholar
  • 52b Kasahara K. Yoshida M. Eishima J. Takesako K. Beppu T. Horinouchi S. J. Antibiot.  1997,  50:  267 
    Google Scholar
  • 52c Achenbach TV. Slater PE. Brummerhop H. Bach T. Müller R. Antimicrob. Agents Chemother.  2000,  44:  2794 
    Google Scholar
  • 52d Kinzy TG. Harger JW. Carr-Schmid A. Kwon J. Shastry M. Justice M. Dinman JD. Virology  2002,  300:  60 
    Google Scholar
  • 53 For a recent review, see: Basler B. Brandes S. Spiegel A. Bach T. Top. Curr. Chem.  2005,  243:  1 
    Google Scholar
  • Three strategies allow the installation of the aryl moiety within 1-3 steps of the final target. Davis generated the C-2 benzyl group in the final step by the reaction of lithium diphenylcuprate with a pyrrolidinylmethyl iodide (40% yield, single diastereomer; 10 steps total, 9% overall yield), see:
  • 54a Davis FA. Deng J. Tetrahedron  2004,  60:  5111 
    Google Scholar
  • Davis has also installed the benzyl moiety through the Horner-Wadsworth-Emmons reaction of a 3-oxopyrrolidin-2-ylphosphonate followed by a two-step reduction sequence (43% yield over 3 steps; 10 steps total, 25% overall yield), see:
  • 54b Davis FA. Zhang J. Qiu H. Wu Y. Org. Lett.  2008,  10:  1433 
    Google Scholar
  • Bach employed the Paternò-Büchi reaction of benzaldehyde with a dihydropyrrole (4:1 dr, 53% yield after separation of the diastereomers) followed by a two-step deprotection sequence to generate the benzyl substituent (39% yield over 3 steps; 9 steps total, 11% overall yield), see:
  • 54c Bach T. Brummerhop H. Angew. Chem. Int. Ed.  1998,  37:  3400 
    Google Scholar
  • This model is also consistent with the stereochemical outcome of reactions involving analogous γ-(arylamino)-alkenes. For further discussion of A(¹,³)-strain in transformations involving N-substituted amines, see:
  • 55a Hoffmann RW. Chem. Rev.  1989,  89:  1841 
    Google Scholar
  • 55b Hart DJ. J. Am. Chem. Soc.  1980,  102:  397 
    Google Scholar
  • 55c Williams RM. Sinclair PJ. Zhai D. Chen D. J. Am. Chem. Soc.  1988,  110:  1547 
    Google Scholar
  • 55d Kano S. Yokomatsu T. Iwasawa H. Shibuya S. Heterocycles  1987,  26:  2805 
    Google Scholar
  • 56 Bertrand MB. Wolfe JP. Org. Lett.  2006,  8:  2353 
    Google Scholar
  • 57a Fritz JA. Nakhla JS. Wolfe JP. Org. Lett.  2006,  8:  2531 
    Google Scholar
  • 57b Fritz JA. Wolfe JP. Tetrahedron  2008,  64:  6838 
    Google Scholar
  • 58 Kazmierski WM. Furfine E. Gray-Nunez Y. Spaltenstein A. Wright L. Bioorg. Med. Chem. Lett.  2004,  14:  5685 
    CrossrefPubMedGoogle Scholar
  • 59 Heidempergher F. Pillan A. Pinciroli V. Vaghi F. Arrigoni C. Bolis G. Caccia C. Dho L. McArthur R. Varasi M. J. Med. Chem.  1997,  40:  3369 
    CrossrefGoogle Scholar
  • 60 Shue H.-J. Chen X. Schwerdt JH. Paliwal S. Blythin DJ. Lin L. Gu D. Wang C. Reichard GA. Wang H. Piwinski JJ. Duffy RA. Lachowicz JE. Coffin VL. Nomeir AA. Morgan CA. Varty GB. Shih N.-Y. Bioorg. Med. Chem. Lett.  2006,  16:  1065 
    CrossrefGoogle Scholar
  • 61a Davies SG. Evans GB. Mortlock AA. Tetrahedron: Asymmetry  1994,  5:  585 
    Google Scholar
  • 61b Kubota H. Kubo A. Takahashi M. Shimizu R. Da-te T. Okamura K. Nunami K.-i. J. Org. Chem.  1995,  60:  6776 
    Google Scholar
  • 61c Parisi M. Solo A. Wulff WD. Guzei IA. Rheingold AL. Organometallics  1998,  17:  3696 
    Google Scholar
  • 61d Kise N. Ueda T. Kumada K. Terao Y. Ueda N. J. Org. Chem.  2000,  65:  464 
    Google Scholar
  • 62a Guillena G. Nájera C. J. Org. Chem.  2000,  65:  7310 
    Google Scholar
  • 62b Cardillo G. Orena M. Penna M. Sandri S. Tomasini C. Tetrahedron  1991,  47:  2263 
    Google Scholar
  • 62c Trost BM. Fandrick DR. J. Am. Chem. Soc.  2003,  125:  11836 
    Google Scholar
  • For a review, see:
  • 63a Sartori G. Maggi R. In Science of Synthesis   Vol. 18:  Ley SV. Knight JG. Thieme; Stuttgart: 2005.  p.665 
    Google Scholar
  • For other recent approaches to the synthesis of cyclic ureas, see:
  • 63b Kim M. Mulcahy JV. Espino CG. DuBois J. Org. Lett.  2006,  8:  1073 
    Google Scholar
  • 63c Streuff J. H övelmann CH. Nieger M. Muñiz K. J. Am. Chem. Soc.  2005,  127:  14586 
    Google Scholar
  • 63d Zabawa TP. Kasi D. Chemler SR. J. Am. Chem. Soc.  2005,  127:  11250 
    Google Scholar
  • 63e Kim MS. Kim Y.-W. Hahm HS. Jang JW. Lee WK. Ha H.-J. Chem. Commun.  2005,  3062 ; and references cited therein
    Google Scholar
  • 63f Bar GLJ. Lloyd-Jones GC. Booker-Milburn KI. J. Am. Chem. Soc.  2005,  127:  7308 
    Google Scholar
  • For syntheses of cyclic ureas from acyclic N-allylureas that form both a carbon-carbon and a carbon-nitrogen bond, see:
  • 64a

    See also Ref. 6c.

    Google Scholar
  • 64b Tamaru Y. Hojo M. Higashimura H. Yoshida Z.-i. J. Am. Chem. Soc.  1988,  110:  3994 
    Google Scholar
  • 64c Danishefsky S. Taniyama E. Webb RR. Tetrahedron Lett.  1983,  24:  11 
    Google Scholar
  • 65a Ishiyama H. Tsuda M. Endo T. Kobayashi J. Molecules  2005,  10:  312 
    Google Scholar
  • 65b Minter AR. Brennan BB. Mapp AK. J. Am. Chem. Soc.  2004,  126:  10504 
    Google Scholar
  • 65c Palmer GC. Ordy MJ. Simmons RD. Strand JC. Radov LA. Mullen GB. Kinsolving CR. St. Georgiev V. Mitchell JT. Allen SD. Antimicrob. Agents Chemother.  1989,  33:  895 
    Google Scholar
  • 66 For a review on the use of isoxazolidines as intermediates in complex molecule syntheses, see: Frederickson M. Tetrahedron  1997,  53:  403 
    CrossrefGoogle Scholar
  • 67a Lait SM. Rankic DA. Keay BA. Chem. Rev.  2007,  107:  767 
    Google Scholar
  • 67b Revuelta J. Cicchi S. Brandi A. Tetrahedron Lett.  2004,  45:  8375 
    Google Scholar
  • 67c LeBel NA. Balasubramanian N. J. Am. Chem. Soc.  1989,  111:  3363 
    Google Scholar
  • 67d Iida H. Kasahara K. Kibayashi C. J. Am. Chem. Soc.  1986,  108:  4647 
    Google Scholar
  • For reviews on 1,3-dipolar cycloaddition reactions of nitrones, see:
  • 68a Confalone PN. Huie EM. Org. React.  1988,  36:  1 
    Google Scholar
  • 68b Gothelf KV. Jorgensen KA. Chem. Commun.  2000,  1449 
    Google Scholar
  • 68c Kanemasa S. Synlett  2002,  1371 
    Google Scholar
  • 69 Murahashi S.-I. Mitsui H. Shiota T. Tsuda T. Watanabe S. J. Org. Chem.  1990,  55:  1736 
    CrossrefGoogle Scholar
  • 70 Biloski AJ. Ganem B. Synthesis  1983,  537 
    Article in Thieme ConnectGoogle Scholar
  • 71 Hay MB. Wolfe JP. Angew. Chem. Int. Ed.  2007,  46:  6492 
    CrossrefGoogle Scholar
  • 72 For related studies, see: Jiang D. Peng J. Chen Y. Tetrahedron  2008,  64:  1641 
    CrossrefGoogle Scholar
  • For Pd-catalyzed carboamination reactions of O-butenyl-hydroxylamine derivatives with aryl bromides that afford isoxazolidine products, see:
  • 73a Peng J. Jiang D. Lin W. Chen Y. Org. Biomol. Chem.  2007,  5:  1391 
    Google Scholar
  • 73b Peng J. Lin W. Yuan S. Chen Y. J. Org. Chem.  2007,  72:  3145 
    Google Scholar
  • 73c Dongol KG. Tay BY. Tetrahedron Lett.  2006,  47:  927 
    Google Scholar
  • 74 For Pd-catalyzed carboetherification reactions of β,γ-unsaturated oximes with aryl bromides which afford isoxazoline products, see: Jiang D. Peng J. Chen Y. Org. Lett.  2008,  10:  1695 
    CrossrefGoogle Scholar
  • 75 Iida H. Watanabe Y. Kibayashi C. J. Chem. Soc., Perkin Trans. 1  1985,  261 
    CrossrefGoogle Scholar
  • 76 Nilsson JW. Thorstensson F. Kvarnström I. Oprea T. Samuelsson B. Nilsson I. J. Comb. Chem.  2001,  3:  546 
    CrossrefGoogle Scholar
  • 77a Chu-Moyer MY. Ballinger WE. Beebe DA. Berger R. Coutcher JB. Day WW. Li J. Mylari BL. Oates PJ. Weekly RM. J. Med. Chem.  2002,  45:  511 
    Google Scholar
  • 77b Zheng G. Dwoskin LP. Deaciuc AG. Zhu J. Jones MD. Crooks PA. Bioorg. Med. Chem.  2005,  13:  3899 
    Google Scholar
  • 78a Schanen V. Cherrier M.-P. de Melo SJ. Quirion J.-C. Husson H.-P. Synthesis  1996,  833 
    Google Scholar
  • 78b Mickelson JW. Belonga KL. Jacobsen EJ. J. Org. Chem.  1995,  60:  4177 
    Google Scholar
  • 78c Mickelson JW. Jacobsen EJ. Tetrahedron: Asymmetry  1995,  6:  19 
    Google Scholar
  • 78d Cochran BM. Michael FE. Org. Lett.  2008,  10:  329 
    Google Scholar
  • 79 Jung ME. Piizzi G. Chem. Rev.  2005,  105:  1735 
    CrossrefPubMedGoogle Scholar
  • 80 Ma D. Zhang Y. Yao J. Wu S. Tao F. J. Am. Chem. Soc.  1998,  120:  12459 
    CrossrefGoogle Scholar
  • 81 DEPBT = 3-(diethoxyphosphoryloxy)-1,2,3-benzotriazin-4(3H)-one. The use of other reagents (e.g., DCC/HOBt or CDI) resulted in partial epimerization to afford products with ca. 85-90% ee, see: Li H. Jiang X. Ye Y.-h. Fan C. Romoff T. Goodman M. Org. Lett.  1999,  1:  91 
    CrossrefPubMedGoogle Scholar
  • 83 Nakhla JS. Wolfe JP. Org. Lett.  2007,  9:  3279 
    CrossrefGoogle Scholar
21

Rossi, M. A.; Wolfe, J. P. unpublished results.

23

Definitions of ligands (see also Figure  [³] ):
Dpe-phos = bis[2-(diphenylphosphino)phenyl] ether; Xantphos = 9,9-dimethyl-4,5-bis(diphenylphosphino)-xanthene; NiXantphos = 4,6-bis(diphenylphosphino)-phenoxazine; dppe = 1,2-bis(diphenylphosphino)ethane;
dppp = 1,3-bis(diphenylphosphino)propane; dppb = 1,4-bis-(diphenylphosphino)butane.

28

A small amount of a regioisomer analogous to 18 was also formed in this reaction.

31

Lira, R.; Wolfe, J. P. unpublished results.

37

We have recently developed conditions to effect the Pd-catalyzed carboamination of N-Boc- and N-acyl-protected substrates bearing 1,1- and 1,2-disubstituted alkenes: Bertrand, M. B.; Neukom, J. D.; Wolfe, J. P. J. Org. Chem. 2008, in press; DOI: 10.1021/jo801631v.

82

Surprisingly, the stereochemical outcome of the piperazine-forming reactions is opposite to that predicted by the allylic strain model, similar to that shown in Scheme  [¹¹] . Our current working hypothesis suggests that the piperazine-forming reactions proceed through a transition state in which the N-aryl group is rotated to minimize allylic strain interactions, and the structure around the cyclizing nitrogen atom is pyramidal. Investigations into this hypothesis are currently underway.