Hydroxylamine Oxygen as Nucleophile in Palladium(0)- and Palladium(II)-Catalyzed Allylic Alkylation: A Novel Access to Isoxazolidines

Pedro Merino; Tomas Tejero; Vanni Mannucci; Guillaume Prestat; David Madec; Giovanni Poli

doi:10.1055/s-2007-973868

LETTER

Hydroxylamine Oxygen as Nucleophile in Palladium(0)- and Palladium(II)-Catalyzed Allylic Alkylation: A Novel Access to Isoxazolidines

Pedro Merino*^a, Tomas Tejero^a, Vanni Mannucci^a,b, Guillaume Prestat^b, David Madec^b, Giovanni Poli*^b
^a Laboratorio de Sintesis Asimetrica, Departamento de Quimica Organica, Instituto de Ciencia de Materiales de Aragon, Universidad de Zaragoza, CSIC, 50009 Zaragoza, Aragon, Spain
Fax: +34(976)762075; e-Mail: pmerino@unizar.es;
^b Université Pierre et Marie Curie-Paris 6, Laboratoire de Chimie Organique (UMR CNRS 7611), Institut de Chimie Moléculaire (FR 2769), Case 183, 4 Place Jussieu, 75252 Paris Cedex 05, France
Fax: +33(1)44277567; e-Mail: giovanni.poli@upmc.fr;

Abstract

All articles of this category

Abstract

In search for novel heterocyclization processes, the intramolecular Pd-mediated allylic alkylation of homoallyl hydroxylamines is described. Depending on both the reaction conditions and the substrates, cis- or trans-3-substituted-5-vinyl isoxazolidines are preferentially obtained. The corresponding starting materials for the cyclization step are readily obtained through cross-metathesis of the easily accessible unsubstituted homoallyl hydroxylamines.

Key words

palladium - ring closure - hydroxylamines - allyl complexes - isoxazolidines

Full Text

References

References and Notes

<A NAME="RG00807ST-1A">1a</A> Alonso F. Beletskaya IP. Yus M. Chem. Rev. 2004, 104: 3079

<A NAME="RG00807ST-1B">1b</A> Nakamura I. Yamamoto Y. Chem. Rev. 2004, 104: 2127

<A NAME="RG00807ST-2A">2a</A> Hosokawa T. Murahashi S.-I. Intramolecular Oxypalladation, In Handbook of Organopalladium Chemistry for Organic Synthesis Vol. 2: Negishi E.-I. John Wiley and Sons; New York: 2002. p.2169

<A NAME="RG00807ST-2B">2b</A> Zeni G. Larock RC. Chem. Rev. 2004, 104: 2285

For reviews, see:

<A NAME="RG00807ST-3A">3a</A> Tsuji J. In Handbook of Organopalladium Chemistry for Organic Synthesis Vol. 1: Negishi E.-I. John Wiley and Sons; New York: 2002. p.1669

<A NAME="RG00807ST-3B">3b</A> Trost BM. Vranken DLV. Chem. Rev. 1996, 96: 395

<A NAME="RG00807ST-3C">3c</A> Hegedus LS. Transition Metals in the Synthesis of Complex Organic Molecules University Science Book; Mill Valley: 1994.

<A NAME="RG00807ST-4">4</A> Miyabe H. Yoshida K. Reddy VK. Matsumura A. Takemoto Y. J. Org. Chem. 2005, 70: 5630

<A NAME="RG00807ST-5">5</A> Miyabe H. Yoshida K. Yamauchi M. Takemoto Y. J. Org. Chem. 2005, 70: 2148

<A NAME="RG00807ST-6">6</A> Frederickson M. Tetrahedron 1997, 53: 403

<A NAME="RG00807ST-7">7</A> Merino P. In Science of Synthesis Vol. 27: Padwa A. Georg Thieme Verlag; New York: 2004. p.511

<A NAME="RG00807ST-8">8</A> Merino P. In Targets in Heterocyclic Systems: Chemistry and Properties Vol. 7: Attanasi OA. Spinelli D. Italian Society of Chemistry; Rome: 2003. p.140

To the best of our knowledge, the only precedent so far reported (see ref. 5) deals with intermolecular reactions, using carbonates as leaving groups, and necessitating an electron-withdrawing group on the hydroxylamine nitrogen atom.

<A NAME="RG00807ST-10A">10a</A> Merino P. Delso I. Mannucci V. Tejero T. Tetrahedron Lett. 2006, 47: 3311

<A NAME="RG00807ST-10B">10b</A> Laskar DD. Prajapati D. Sandhu JS. Tetrahedron Lett. 2001, 42: 7883

<A NAME="RG00807ST-10C">10c</A> Kumar HMS. Anjaneyulu S. Reddy EJ. Yadav JS. Tetrahedron Lett. 2000, 41: 9311

<A NAME="RG00807ST-11">11</A> Merino P. Mannucci V. Tejero T. Tetrahedron 2005, 61: 3335

Alkene 5 has been successfully used in ruthenium-catalyzed cross-metathesis reactions. For representative examples, see:

<A NAME="RG00807ST-12A">12a</A> Blackwell HE. O’Leary DJ. Chatterjee AK. Washenfelder RA. Bussmann DA. Grubbs RH. J. Am. Chem. Soc. 2000, 122: 58

<A NAME="RG00807ST-12B">12b</A> Chatterjee AK. Sanders DP. Grubbs RH. Org. Lett. 2002, 11: 1939

<A NAME="RG00807ST-12C">12c</A> Chatterjee AK. Toste FD. Choi T.-L. Grubbs RH. Adv. Synth. Catal. 2002, 344: 634

<A NAME="RG00807ST-12D">12d</A> Chatterjee AK. Choi T.-L. Sanders DP. Grubbs RH. J. Am. Chem. Soc. 2003, 125: 11360

<A NAME="RG00807ST-12E">12e</A> Cluzeau J. Capdevielle P. Cossy J. Tetrahedron Lett. 2005, 40: 6945

<A NAME="RG00807ST-13A">13a</A> Kingsbury JS. Harrity JPA. Bonitatebus PJ. Hoveyda AH. J. Am. Chem. Soc. 1999, 121: 791

<A NAME="RG00807ST-13B">13b</A> Garber SB. Kingsbury JS. Gray BL. Hoveyda AH. J. Am. Chem. Soc. 2000, 122: 8168

<A NAME="RG00807ST-13C">13c</A> Grubbs RH. Trnka TM. In Ruthenium in Organic Synthesis Murahashi S.-I. Wiley-VCH; New York: 2004. p.153-177

It has been recently described that the use of Lewis acids can prevent undesired coordination of N-atom to the ruthenium carbene intermediate in metathesis reactions:

<A NAME="RG00807ST-14A">14a</A> Yang Q. Xiao W.-J. Yu Z. Org. Lett. 2005, 7: 871

<A NAME="RG00807ST-14B">14b</A> See also: Fürstner A. Langemann K. J. Am. Chem. Soc. 1997, 119: 9130

Use of tert-butyldimethylsilyl chloride in the presence of several tertiary amines failed to give the corresponding protected hydroxylamine.

Data for 6a: (90%). R _f = 0.55 (hexane-EtOAc, 4:1); oil. ¹H NMR (400 MHz, CDCl₃, 25 °C, mixture of conformers): δ = 7.27-7.22 (m, 3 H), 7.21-7.13 (m, 4 H), 7.04-6.98 (m, 3 H), 5.61-5.55 (m, 1.6 H), 5.54-5.43 (m, 0.4 H), 4.58-4.50 (m, 0.4 H), 4.41-4.37 (m, 1.6 H), 4.20 (t, 1 H, J = 7.5 Hz), 2.79 (t, 2 H, J = 6.7 Hz), 2.06 (br, 0.6 H), 2.02 (br, 2.4 H), 0.3 (br, 9 H), -0.07 (br, 3 H), -0.31 (br, 0.6 H), -0.34 (br, 2.4 H). ¹³C NMR (100 MHz, CDCl₃, 25 °C, selected signals for the major conformer): δ = 170.7, 152,5, 137.8, 133.3, 131.9, 127.9, 127.5, 127.4, 125.8, 123.7, 121.2, 74.3, 65.0, 32.9, 26.1, 21.0, 18.0, -4.7, -5.5. Anal Calcd for C₂₅H₃₅NO₃Si: C, 70.55; H, 8.29; N, 3.29. Found: C, 70.59; H, 8.45; N, 3.22.

<A NAME="RG00807ST-17">17</A> Hyland C. Tetrahedron 2005, 61: 3457

<A NAME="RG00807ST-18A">18a</A> Lu X. Zhang Q. J. Am. Chem. Soc. 2000, 122: 7604

<A NAME="RG00807ST-18B">18b</A> Lei A. Liu G. Lu X. J. Org. Chem. 2002, 67: 974

<A NAME="RG00807ST-18C">18c</A> Miyazawa M. Hirose Y. Narantsetseg M. Yokoyama H. Yamaguchi S. Hirai Y. Tetrahedron Lett. 2004, 45: 2883

<A NAME="RG00807ST-18D">18d</A> Yokoyama H. Otaya K. Kobayashi H. Miyazawa M. Yamaguchi S. Hirai Y. Org. Lett. 2000, 2: 2427

<A NAME="RG00807ST-18E">18e</A> Ferber B. Prestat G. Vogel S. Madec D. Poli G. Synlett 2006, 2133

<A NAME="RG00807ST-19">19</A> We recently reported a related comparative study of Pd(0) vs. nonoxidative Pd(II) catalysis for intramolecular allylic amination, see ref. 18e and: Ferber B. Lemaire S. Mader MM. Prestat G. Poli G. Tetrahedron Lett. 2003, 44: 4213

General Procedure for the Pd(0)-Mediated Intramolecular Allylic Alkylation The proper homoallylhydroxylamine (1 mmol) and (if needed) NaH (60% dispersion in a mineral oil, 1 mmol) were dissolved in DMF (20 mL) under an argon atmosphere and the resulting mixture was cooled to 0 °C. In a separate flask, Pd(OAc)₂ (5 mol%) and dppe (10 mol%) were mixed in DMF (5 mL) and stirred for ca 5 min. After having carefully verified that the initially brown solution turned into a paler brown suspension, the thus formed Pd(0) catalyst was added into the solution of hydroxylamine. The resulting mixture was stirred at r.t. for 30 min, then heated at 80 °C for 3 h. After cooling to r.t., the solution was poured into Et₂O (125 mL) and H₂O (50 mL) was added. The organic layer was separated and the aqueous layer was extracted with Et₂O. The combined organic extracts were washed with brine, dried over MgSO₄, filtered and evaporated under reduced pressure to give a residue which was purified by radial chromatography.

General Procedure for the Pd(II)-Mediated Intramolecular Allylic Alkylation The corresponding homoallylhydroxylamine (1 mmol), Pd(OAc)₂ (10 mol%) and lithium halide (5 mmol; if needed) were dissolved in DMF (20 mL) under an argon atmosphere. The resulting mixture was stirred at r.t. for 30 min, then heated at 80 °C for 3 h. After cooling to r.t., the solution was poured into Et₂O (125 mL) and H₂O (50 mL) was added. The organic layer was separated and the aqueous layer was extracted with Et₂O. The combined organic extracts were washed with brine, dried over MgSO₄, filtered and evaporated under reduced pressure to give a residue which was purified by radial chromatography.

The relative stereochemical assignment of compound 8a was based on ROESY experiments.

In situ preformation of Pd(0) from Pd(OAc)₂/phosphine is amply documented. See for example:

<A NAME="RG00807ST-23A">23a</A> Amatore C. Carre E. Jutand A. M’Barke MA. Organometallics 1995, 14: 1818

<A NAME="RG00807ST-23B">23b</A> Amatore C. Jutand A. Thuilliez A. Organometallics 2001, 20: 3241

<A NAME="RG00807ST-23C">23c</A> Shimizu I. Tsuji J. J. Am. Chem. Soc. 1982, 104: 5844

Submission of compounds 9 and 11 to the same reaction conditions as in entries 3 and 6 of Table [2] , but in the absence of Pd(OAc)₂, gave only starting material, thereby ruling out the possibility of a noncatalytic cyclization passing through the corresponding allylic bromide.

Data for 10: R _f = 0.36 (hexane-EtOAc, 4:1); [α]_D ²⁰ +92 (c 0.16, CHCl₃). ¹H NMR (400 MHz, CDCl₃, 25 °C): δ = 7.45-7.40 (m, 2 H), 7.37-7.31 (m, 2 H), 7.30-7.24 (m, 1 H), 5.85 (ddd, 1 H, J = 17.2, 10.3, 7.1 Hz), 5.29 (d, 1 H, J = 17.2 Hz), 5.18 (d, 1 H, J = 10.3 Hz), 4.47 (dt, 1 H, J = 7.6, 7.1 Hz), 4.34 (d, 1 H, J = 14.0 Hz), 4.15 (dt, 1 H, J = 7.1, 6.5 Hz), 4.04 (dd, 1 H, J = 8.3, 6.5 Hz), 4.00 (d, 1 H, J = 14.0 Hz), 3.74 (dd, 1 H, J = 8.3, 7.1 Hz), 3.13 (dt, 1 H, J = 8.2, 7.1 Hz), 2.21-2.04 (m, 2 H), 1.44 (s, 3 H), 1.36 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃, 25 °C): δ = 137.6, 137.2, 129.2, 128.2, 127.2, 117.5, 109.8, 78.4, 77.2, 67.2, 66.9, 62.2, 37.5, 26.7, 25.4. Anal. Calcd for C₁₇H₂₃NO₃: C, 70.56; H, 8.01; N, 4.84. Found: C, 70.47; H, 8.13; N, 4.76.

Data for 12: R _f = 0.42 (hexane-EtOAc, 4:1); [α]_D ²⁰ +21 (c 1.38, CHCl₃). ¹H NMR (400 MHz, CDCl₃, 25 °C): δ = 7.31-7.17 (m, 5 H), 5.89-5.79 (ddd, 1 H, J = 17.1, 10.2, 7.4 Hz), 5.20 (dt, 1 H, J = 17.1, 1.2 Hz), 5.10 (dt, 1 H, J = 10.2, 1.2 Hz), 4.50 (q, 1 H, J = 7.4 Hz), 4.04 (d, 1 H, J = 12.8 Hz), 3.98-3.92 (m, 2 H), 3.77 (d, 1 H, J = 12.8 Hz), 3.47-3.40 (m, 1 H), 3.16-3.10 (t, 1 H, J = 6.9 Hz), 2.48 (dddd, 1 H, J = 12.8, 9.2, 7.4, 1.6 Hz), 2.15 (ddd, 1 H, J = 12.8, 9.2, 7.4 Hz), 1.27 (s, 3 H), 1.24 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃, 25 °C): δ = 138.2, 137.0, 129.3, 128.5, 127.6, 117.3, 109.3, 80.4, 75.7, 68.0, 67.4, 63.6, 36.1, 26.8, 25.3. Anal. Calcd for C₁₇H₂₃NO₃: C, 70.56; H, 8.01; N, 4.84. Found: C, 70.70; H, 7.88; N, 5.01.