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

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

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 

1b Saleem M. Kim HJ. Ali MS. Lee YS. Nat. Prod. Rep.  2005,  22:  696 

1c Bermejo A. Figadere B. Zafra-Polo M.-C. Barrachina I. Estornell E. Cortes D. Nat. Prod. Rep.  2005,  22:  269 

1d Daly JW. Spande TF. Garraffo HM. J. Nat. Prod.  2005,  68:  1556 

1e Hackling AE. Stark H. ChemBioChem  2002,  3:  946 

1f Lewis JR. Nat. Prod. Rep.  2001,  18:  95 

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 

2b Chemler SR. Fuller PH. Chem. Soc. Rev.  2007,  36:  1153 

2c Minatti A. Muniz K. Chem. Soc. Rev.  2007,  36:  1142 

2d Zeni G. Larock RC. Chem. Rev.  2006,  106:  4644 

2e Conreaux D. Bouyssi D. Monteiro N. Balme G. Curr. Org. Chem.  2006,  10:  1325 

2f Muzart J. Tetrahedron  2005,  61:  5955 

2g Wolfe JP. Thomas JS. Curr. Org. Chem.  2005,  9:  625 

2h Nakamura I. Yamamoto Y. Chem. Rev.  2004,  104:  2127 

2i Zeni G. Larock RC. Chem. Rev.  2004,  104:  2285 

2j Deiters A. Martin SF. Chem. Rev.  2004,  104:  2199 

2k Barluenga J. Santamaria J. Tomas M. Chem. Rev.  2004,  104:  2259 

2l McReynolds MD. Dougherty JM. Hanson PR. Chem. Rev.  2004,  104:  2239 

For reviews on the synthesis of tetrahydrofurans, see:

3a Wolfe JP. Hay MB. Tetrahedron  2007,  63:  261 

3b Miura K. Hosomi A. Synlett  2003,  143 

3c Koert U. Synthesis  1995,  115 

3d Harmange J.-C. Figadere B. Tetrahedron: Asymmetry  1993,  4:  1711 

3e Cardillo G. Orena M. Tetrahedron  1990,  46:  3321 

3f Boivin TLB. Tetrahedron  1987,  43:  3309 

For reviews on the synthesis of pyrrolidines, see:

4a Bellina F. Rossi R. Tetrahedron  2006,  62:  7213 

4b Coldham I. Hufton R. Chem. Rev.  2005,  105:  2765 

4c Pyne SG. Davis AS. Gates NJ. Hartley JP. Lindsay KB. Machan T. Tang M. Synlett  2004,  2670 

4d Felpin F.-X. Lebreton J. Eur. J. Org. Chem.  2003,  3693 

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 

5b Kang S.-K. Baik T.-G. Kulak AN. Synlett  1999,  324 

5c Jacobi PA. Liu H. Org. Lett.  1999,  1:  341 

5d Walkup RD. Guan L. Mosher MD. Kim SW. Kim YS. Synlett  1993,  88 

5e Luo FT. Schreuder I. Wang RT. J. Org. Chem.  1992,  57:  2213 

5f Luo FT. Wang RT. Tetrahedron Lett.  1992,  33:  6835 

5g Arcadi A. Cacchi S. Marinelli F. Tetrahedron Lett.  1992,  33:  3915 

5h Davies IW. Scopes DIC. Gallagher T. Synlett  1993,  85 

5i Wolf LB. Tjen KCMF. Rutjes FPJT. Hiemstra H. Schoemaker HE. Tetrahedron Lett.  1998,  39:  5081 

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 

6b Sherman ES. Chemler SR. Tan TB. Gerlits O. Org. Lett.  2004,  6:  1573 

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 

For carboamination reactions between alkenes and N-allylsulfonamides, see:

6d Scarborough CC. Stahl SS. Org. Lett.  2006,  8:  3251 

For carboamination reactions of vinylcyclopropanes, see:

6e Larock RC. Yum EK. Synlett  1990,  529 

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 

6g Semmelhack MF. Zhang N. J. Org. Chem.  1989,  54:  4483 

6h McCormick M. Monahan R. Soria J. Goldsmith D. Liotta D. J. Org. Chem.  1989,  54:  4485 

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

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 

7b Harris GD. Herr RJ. Weinreb SM. J. Org. Chem.  1993,  58:  5452 

7c Larock RC. Yang H. Weinreb SM. Herr RJ. J. Org. Chem.  1994,  59:  4172 

8 For a review on Pd(0)- and Pd(II)-catalyzed carboetherification and carboamination reactions, see: Wolfe JP. Eur. J. Org. Chem.  2007,  571 

9 Crabtree RH. The Organometallic Chemistry of the Transition Metals   4th ed.:  John Wiley and Sons; Hoboken NJ: 2005. 

10a Yamamoto A. J. Chem. Soc., Dalton Trans.  1999,  1027 

10b Beletskaya IP. Cheprakov AV. Chem. Rev.  2000,  100:  3009 

11a Lin BL. Clough CR. Hillhouse GL. J. Am. Chem. Soc.  2002,  124:  2890 

11b Koo K. Hillhouse GL. Organometallics  1995,  14:  4421 

11c Matsunaga PT. Hillhouse GL. Rheingold AL. J. Am. Chem. Soc.  1993,  115:  2075 

11d Koo K. Hillhouse GL. Organometallics  1998,  17:  2924 

11e Williams BS. Goldberg KI. J. Am. Chem. Soc.  2001,  123:  2576 

11f Brice JL. Harang JE. Timokhin VI. Anastasi NR. Stahl SS. J. Am. Chem. Soc.  2005,  127:  2868 

11g Dick AR. Kampf JW. Sanford MS. J. Am. Chem. Soc.  2005,  127:  12790 

12a Hosokawa T. Murahashi S.-I. Acc. Chem. Res.  1990,  23:  49 

12b Hegedus LS. Angew. Chem., Int. Ed. Engl.  1988,  27:  1113 

13a Muci AR. Buchwald SL. Top. Curr. Chem.  2002,  219:  131 

13b Hartwig JF. Pure Appl. Chem.  1999,  71:  1417 

14a Villanueva LA. Abboud KA. Boncella JM. Organometallics  1992,  11:  2963 

14b VanderLende DD. Abboud KA. Boncella JM. Inorg. Chem.  1995,  34:  5319 

14c Cowan RL. Trogler WC. J. Am. Chem. Soc.  1989,  111:  4750 

14d Bryndza HE. Organometallics  1985,  4:  406 ; and references cited therein

14e Bennett MA. Jin H. Li S. Rendina LM. Willis AC. J. Am. Chem. Soc.  1995,  117:  8335 

14f Ritter JCM. Bergman RG. J. Am. Chem. Soc.  1997,  119:  2580 

14g Casalnuovo AL. Calabrese JC. Milstein D. J. Am. Chem. Soc.  1988,  110:  6738 

14h Hamed O. Thompson C. Henry PM. J. Org. Chem.  1997,  62:  7082 

14i Nelson DJ. Li R. Brammer C. J. Am. Chem. Soc.  2001,  123:  1564 

For recent studies on alkene insertion into late transition metal-oxygen or -nitrogen bonds, see:

15a

See also ref. 11f

15b Hayashi T. Yamasaki K. Mimura M. Uozumi Y.
J. Am. Chem. Soc.  2004,  126:  3036 

15c Zhao P. Krug C. Hartwig JF. J. Am. Chem. Soc.  2005,  127:  12066 

15d Trend RM. Ramtohul YK. Stoltz BM. J. Am. Chem. Soc.  2005,  127:  17778 

15e Zhao P. Incarvito CD. Hartwig JF. J. Am. Chem. Soc.  2006,  128:  9642 

16 Milstein D. Stille JK. J. Am. Chem. Soc.  1979,  101:  4981 

17 Larock RC. Leung W.-Y. Stoltz-Dunn S. Tetrahedron Lett.  1989,  30:  6629 

18 Fournet G. Balme G. Gore J. Tetrahedron  1990,  46:  7763 

19 Trost BM. Pfrengle W. Urabe H. Dumas J. J. Am. Chem. Soc.  1992,  114:  1923 

20a Wolfe JP. Rossi MA. J. Am. Chem. Soc.  2004,  126:  1620 

20b Hay MB. Hardin AR. Wolfe JP. J. Org. Chem.  2005,  70:  3099 

21

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

22a Widenhoefer RA. Zhong HA. Buchwald SL. J. Am. Chem. Soc.  1997,  119:  6787 

22b Widenhoefer RA. Buchwald SL. J. Am. Chem. Soc.  1998,  120:  6504 

22c Mann G. Hartwig JF. J. Am. Chem. Soc.  1996,  118:  13109 

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.

24a Hay MB. Wolfe JP. J. Am. Chem. Soc.  2005,  127:  16468 

24b Hay MB. Wolfe JP. Tetrahedron Lett.  2006,  47:  2793 

25 Yeh has recently described related carboetherification reactions of dienes, see: Yeh M.-CP. Tsao W.-C. Tu L.-H. Organometallics  2005,  24:  5909 

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 

26b Catellani M. Frignani F. Rangoni A. Angew. Chem., Int. Ed. Engl.  1997,  36:  119 

26c Catellani M. Fagnola MC. Angew. Chem., Int. Ed. Engl.  1994,  33:  2421 

26d Matsumura S. Maeda Y. Nishimura T. Uemura S. J. Am. Chem. Soc.  2003,  125:  8862 

26e Wang X. Stankovich SZ. Widenhoefer RA. Organometallics  2002,  21:  901 ; and references cited therein

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 

28

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

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 

29b

See also ref. 15b

29c

See also ref. 15d

30a Ney JE. Wolfe JP. Angew. Chem. Int. Ed.  2004,  43:  3605 

30b Ney JE. Hay MB. Yang Q. Wolfe JP. Adv. Synth. Catal.  2005,  347:  1614 

31

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

32a Lira R. Wolfe JP. J. Am. Chem. Soc.  2004,  126:  13906 

32b Yang Q. Ney JE. Wolfe JP. Org. Lett.  2005,  7:  2575 

33a Saito S. Hatanaka K. Yamamoto H. Org. Lett.  2000,  2:  1891 

33b Overman LE. Owen CE. Pavan MM. Richards CJ. Org. Lett.  2003,  5:  1809 

33c Taniyama D. Hasegawa M. Tomioka K. Tetrahedron: Asymmetry  1999,  10:  221 

34a Bordwell FG. Algrim DJ. J. Am. Chem. Soc.  1988,  110:  2964 

34b Bordwell FG. Ji G.-Z. J. Am. Chem. Soc.  1991,  113:  8398 

34c Zhang X.-M. Bordwell FG. J. Org. Chem.  1994,  59:  6456 

35a Bertrand MB. Wolfe JP. Tetrahedron  2005,  61:  6447 

35b Bertrand MB. Leathen ML. Wolfe JP. Org. Lett.  2007,  9:  457 

36 Tom NJ. Simon WM. Frost HN. Ewing M. Tetrahedron Lett.  2004,  45:  905 

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.

38 Bertrand MB. Wolfe JP. Org. Lett.  2007,  9:  3073 

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 

39b Catellani M. Chiusoli GP. Ricotti S. Sabini F. Gazz. Chim. Ital.  1985,  115:  685 

39c Catellani M. Ferioli L. Synthesis  1996,  769 

40 Ney JE. Wolfe JP. J. Am. Chem. Soc.  2005,  127:  8644 

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 

41b Driver MS. Hartwig JF. Organometallics  1997,  16:  5706 

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 L_nPd(Ar)(Ot-Bu) complex, see: Shekhar S. Hartwig JF. Organometallics  2007,  26:  340 

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 

43b Zhu G. Lu X. Organometallics  1995,  14:  4899 

43c Zhao H. Ariafard A. Lin Z. Organometallics  2006,  25:  812 ; and references cited therein

For early examples, see:

44a Kasahara A. Izumi T. Takeda T. Imamura H. Bull. Chem. Soc. Jpn.  1974,  47:  183 

44b Andersson C.-M. Larsson J. Hallberg A. J. Org. Chem.  1990,  55:  5757 

For a recent review, see:

44c Oestreich M. Eur. J. Org. Chem.  2005,  783 

For recent reviews, see:

45a Campeau L.-C. Fagnou K. Chem. Commun.  2006,  1253 

45b Catellani M. Synlett  2003,  298 

46a Zhang L. Zetterberg K. Organometallics  1991,  10:  3806 

46b Oestreich M. Dennison PR. Kodanko JJ. Overman LE. Angew. Chem. Int. Ed.  2001,  40:  1439 

46c Clique B. Fabritius C.-H. Couturier C. Monteiro N. Balme G. Chem. Commun.  2003,  272 

47 Lee C.-W. Oh KS. Kim KS. Ahn KH. Org. Lett.  2000,  2:  1213 

48a Gillie A. Stille JK. J. Am. Chem. Soc.  1980,  102:  4933 

48b Driver MS. Hartwig JF. J. Am. Chem. Soc.  1997,  119:  8232 

48c Driver MS. Hartwig JF. J. Am. Chem. Soc.  1996,  118:  7217 

48d Culkin DA. Hartwig JF. Organometallics  2004,  23:  3398 ; and references cited therein

48e van Leeuwen PWNM. Kamer PCJ. Reek JNH. Dierkes P. Chem. Rev.  2000,  100:  2741 

48f Christmann U. Vilar R. Angew. Chem. Int. Ed.  2005,  44:  366 

48g Brown JM. Cooley NA. Chem. Rev.  1988,  88:  1031 

49a Jensen DR. Schultz MJ. Mueller JA. Sigman MS. Angew. Chem. Int. Ed.  2003,  42:  3810 

49b Steinhoff BA. Stahl SS. Org. Lett.  2002,  4:  4179 ; and references cited therein

Ligand substitution reactions of d⁸-Pd(II) complexes generally occur via an associative mechanism, see:

50a

See also ref. 29a

50b Shultz LH. Tempel DJ. Brookhart M. J. Am. Chem. Soc.  2001,  123:  11539 ; and references cited therein. For rare exceptions, see:

50c Bartolome C. Espinet P. Martin-Alvarez JM. Villafane F. Eur. J. Inorg. Chem.  2004,  2326 

50d Louie J. Hartwig JF. J. Am. Chem. Soc.  1995,  117:  11598 

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 

52a Johnson JH. Phillipson DW. Kahle AD.
J. Antibiot.  1989,  42:  1184 

52b Kasahara K. Yoshida M. Eishima J. Takesako K. Beppu T. Horinouchi S. J. Antibiot.  1997,  50:  267 

52c Achenbach TV. Slater PE. Brummerhop H. Bach T. Müller R. Antimicrob. Agents Chemother.  2000,  44:  2794 

52d Kinzy TG. Harger JW. Carr-Schmid A. Kwon J. Shastry M. Justice M. Dinman JD. Virology  2002,  300:  60 

53 For a recent review, see: Basler B. Brandes S. Spiegel A. Bach T. Top. Curr. Chem.  2005,  243:  1 

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 

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 

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 

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 

55b Hart DJ. J. Am. Chem. Soc.  1980,  102:  397 

55c Williams RM. Sinclair PJ. Zhai D. Chen D. J. Am. Chem. Soc.  1988,  110:  1547 

55d Kano S. Yokomatsu T. Iwasawa H. Shibuya S. Heterocycles  1987,  26:  2805 

56 Bertrand MB. Wolfe JP. Org. Lett.  2006,  8:  2353 

57a Fritz JA. Nakhla JS. Wolfe JP. Org. Lett.  2006,  8:  2531 

57b Fritz JA. Wolfe JP. Tetrahedron  2008,  64:  6838 

58 Kazmierski WM. Furfine E. Gray-Nunez Y. Spaltenstein A. Wright L. Bioorg. Med. Chem. Lett.  2004,  14:  5685 

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 

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 

61a Davies SG. Evans GB. Mortlock AA. Tetrahedron: Asymmetry  1994,  5:  585 

61b Kubota H. Kubo A. Takahashi M. Shimizu R. Da-te T. Okamura K. Nunami K.-i. J. Org. Chem.  1995,  60:  6776 

61c Parisi M. Solo A. Wulff WD. Guzei IA. Rheingold AL. Organometallics  1998,  17:  3696 

61d Kise N. Ueda T. Kumada K. Terao Y. Ueda N. J. Org. Chem.  2000,  65:  464 

62a Guillena G. Nájera C. J. Org. Chem.  2000,  65:  7310 

62b Cardillo G. Orena M. Penna M. Sandri S. Tomasini C. Tetrahedron  1991,  47:  2263 

62c Trost BM. Fandrick DR. J. Am. Chem. Soc.  2003,  125:  11836 

For a review, see:

63a Sartori G. Maggi R. In Science of Synthesis   Vol. 18:  Ley SV. Knight JG. Thieme; Stuttgart: 2005.  p.665 

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 

63c Streuff J. H övelmann CH. Nieger M. Muñiz K. J. Am. Chem. Soc.  2005,  127:  14586 

63d Zabawa TP. Kasi D. Chemler SR. J. Am. Chem. Soc.  2005,  127:  11250 

63e Kim MS. Kim Y.-W. Hahm HS. Jang JW. Lee WK. Ha H.-J. Chem. Commun.  2005,  3062 ; and references cited therein

63f Bar GLJ. Lloyd-Jones GC. Booker-Milburn KI. J. Am. Chem. Soc.  2005,  127:  7308 

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.

64b Tamaru Y. Hojo M. Higashimura H. Yoshida Z.-i. J. Am. Chem. Soc.  1988,  110:  3994 

64c Danishefsky S. Taniyama E. Webb RR. Tetrahedron Lett.  1983,  24:  11 

65a Ishiyama H. Tsuda M. Endo T. Kobayashi J. Molecules  2005,  10:  312 

65b Minter AR. Brennan BB. Mapp AK. J. Am. Chem. Soc.  2004,  126:  10504 

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 

66 For a review on the use of isoxazolidines as intermediates in complex molecule syntheses, see: Frederickson M. Tetrahedron  1997,  53:  403 

67a Lait SM. Rankic DA. Keay BA. Chem. Rev.  2007,  107:  767 

67b Revuelta J. Cicchi S. Brandi A. Tetrahedron Lett.  2004,  45:  8375 

67c LeBel NA. Balasubramanian N. J. Am. Chem. Soc.  1989,  111:  3363 

67d Iida H. Kasahara K. Kibayashi C. J. Am. Chem. Soc.  1986,  108:  4647 

For reviews on 1,3-dipolar cycloaddition reactions of nitrones, see:

68a Confalone PN. Huie EM. Org. React.  1988,  36:  1 

68b Gothelf KV. Jorgensen KA. Chem. Commun.  2000,  1449 

68c Kanemasa S. Synlett  2002,  1371 

69 Murahashi S.-I. Mitsui H. Shiota T. Tsuda T. Watanabe S. J. Org. Chem.  1990,  55:  1736 

70 Biloski AJ. Ganem B. Synthesis  1983,  537 

71 Hay MB. Wolfe JP. Angew. Chem. Int. Ed.  2007,  46:  6492 

72 For related studies, see: Jiang D. Peng J. Chen Y. Tetrahedron  2008,  64:  1641 

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 

73b Peng J. Lin W. Yuan S. Chen Y. J. Org. Chem.  2007,  72:  3145 

73c Dongol KG. Tay BY. Tetrahedron Lett.  2006,  47:  927 

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 

75 Iida H. Watanabe Y. Kibayashi C. J. Chem. Soc., Perkin Trans. 1  1985,  261 

76 Nilsson JW. Thorstensson F. Kvarnström I. Oprea T. Samuelsson B. Nilsson I. J. Comb. Chem.  2001,  3:  546 

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 

77b Zheng G. Dwoskin LP. Deaciuc AG. Zhu J. Jones MD. Crooks PA. Bioorg. Med. Chem.  2005,  13:  3899 

78a Schanen V. Cherrier M.-P. de Melo SJ. Quirion J.-C. Husson H.-P. Synthesis  1996,  833 

78b Mickelson JW. Belonga KL. Jacobsen EJ. J. Org. Chem.  1995,  60:  4177 

78c Mickelson JW. Jacobsen EJ. Tetrahedron: Asymmetry  1995,  6:  19 

78d Cochran BM. Michael FE. Org. Lett.  2008,  10:  329 

79 Jung ME. Piizzi G. Chem. Rev.  2005,  105:  1735 

80 Ma D. Zhang Y. Yao J. Wu S. Tao F. J. Am. Chem. Soc.  1998,  120:  12459 

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 

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.

83 Nakhla JS. Wolfe JP. Org. Lett.  2007,  9:  3279