Copper-Catalyzed Ring-Opening of Heterobicyclic Alkenes with Grignard Reagents: Remarkably High anti-Stereocontrol

Abstract

Unlike most of the reported protocols for the ring-opening reaction of heterobicyclic alkenes with carbon nucleophiles which typically occur with syn selectivity, the alkylative ring-opening reaction of [2.2.1]oxa- and azabicyclic alkenes with Grignard reagents in the presence of a catalytic amount of copper(I) takes place with very high or complete anti-stereocontrol under smooth reaction conditions. This new procedure proved to be wide in scope with respect to both the Grignard reagent and the bicyclic alkene. Especially noteworthy is the facile ring-opening reaction of low reactive substrates such as nonaromatic oxabicyclic alkenes and azabenzonorbornadienes under this catalyst system.

Key words

ring-opening reaction - copper catalyst - oxabicyclic alkenes - azabenzonorbornadiene - Grignard reagents - (2-pyridyl)sulfonamides

References

• For recent reviews, see:
• 1a Lautens M. Synthesis  1993,  177 
• 1b Chiu P. Lautens M. Top. Curr. Chem.  1997,  190:  1 
• 1c Lautens M. Fagnou K. Hiebert S. Acc. Chem. Res.  2003,  36:  48 
• For natural product synthesis using this strategy, see:
• 2a Lautens M. Rovis T. J. Org. Chem.  1997,  62:  5246 
• 2b Lautens M. Rovis T. Tetrahedron  1999,  55:  8967 
• 2c Lautens M. Colucci JT. Hiebert S. Smith ND. Bouchain G. Org. Lett.  2002,  4:  1879 
• 2d Lautens M. Fagnou K. Zunic V. Org. Lett.  2002,  4:  3465 
• 3a Caple R. Chen GM.-S. Nelson JD. J. Org. Chem.  1971,  36:  2874 
• 3b Arjona O. de la Pradilla RF. García E. Martín-Domenech A. Plumet J. Tetrahedron Lett.  1989,  30:  6437 
• 3c Lautens M. Gajda C. Chiu P. J. Chem. Soc., Chem. Commun.  1993,  1193 
• 4 Lautens M. Smith AC. Abd-El-Aziz AS. Huboux AH. Tetrahedron Lett.  1990,  31:  3253 
• 6a Lautens M. Renaud J.-L. Hiebert S. J. Am. Chem. Soc.  2000,  122:  1804 
• 6b Lautens M. Hiebert S. Renaud J.-L. Org. Lett.  2000,  2:  1971 
• 6c Lautens M. Hiebert S. Renaud J.-L. J. Am. Chem. Soc.  2001,  123:  6834 
• 6d Priego J. García Mancheño O. Cabrera S. Gómez Arrayás R. Llamas T. Carretero JC. Chem. Commun.  2002,  2512 
• 6e Lautens M. Hiebert S. J. Am. Chem. Soc.  2004,  126:  1437 
• 6f Cabrera S. Gómez Arrayás R. Carretero JC. Angew. Chem. Int. Ed.  2004,  43:  3944 
• 6g Dotta P. Kuwar PGA. Pregosin PS. Albinati A. Rizzato S. Organometallics  2004,  23:  2295 
• 6h Li M. Yan X.-X. Hong W. Zhu X.-Z. Cao B.-X. Sun J. Hou X.-L. Org. Lett.  2004,  6:  2833 
• 6i Imamoto T. Sugita K. Yoshida K. J. Am. Chem. Soc.  2005,  127:  11934 
• 6j Cabrera S. Gómez Arrayás R. Alonso I. Carretero JC. J. Am. Chem. Soc.  2005,  127:  17938 
• 7 Fugami K. Hagiwara S. Oda H. Kosugi M. Synlett  1998,  477 
• 8 Millward DB. Sammis G. Waymouth RM. J. Org. Chem.  2000,  65:  3902 
• 9 Wu M.-S. Rayabarapu DK. Cheng C.-H. J. Org. Chem.  2004,  69:  8407 
• 10 Rayabarapu DK. Chiou C.-F. Cheng C.-H. Org. Lett.  2002,  4:  1679 
• 11a Murakami M. Igawa H. Chem. Commun.  2002,  390 
• 11b Lautens M. Dockendorff C. Fagnou K. Malicki A. Org. Lett.  2002,  4:  1311 
• 12a Duan J.-P. Cheng C.-H. Tetrahedron Lett.  1993,  34:  4019 
• 12b Duan J.-P. Cheng C.-H. Organometallics  1995,  14:  1608 
• 13 Feng C.-C. Nandi M. Sambaiah T. Cheng C.-H. J. Org. Chem.  1999,  64:  3538 
• 14 Rayabarapu DK. Cheng C.-H. Chem. Eur. J.  2003,  9:  3164 
• 15a Lautens M. Fagnou K. J. Am. Chem. Soc.  2001,  123:  7170 
• 15b Lautens M. Schmid GA. Chau A. J. Org. Chem.  2002,  67:  8043 
• 15c Lautens M. Fagnou K. Yang D. J. Am. Chem. Soc.  2003,  125:  14884 
• 16 Bertozzi F. Pineschi M. Macchia F. Arnold LA. Minnaard AJ. Feringa BL. Org. Lett.  2002,  4:  2703 
• 17 See also: Li L.-P. Rayabarapu DK. Nandi M. Cheng C.-H. Org. Lett.  2003,  5:  1621 
• 18a Lautens M. Fagnou K. Rovis T. J. Am. Chem. Soc.  2000,  122:  5650 
• 18b Lautens M. Fagnou K. Taylor M. Org. Lett.  2000,  2:  1677 
• 18c Lautens M. Fagnou K. Tetrahedron  2001,  57:  5067 
• 18d Lautens M. Fagnou K. Taylor M. Rovis T. J. Organomet. Chem.  2001,  624:  259 
• 18e Lautens M. Fagnou K. Proc. Natl. Acad. Sci. U.S.A.  2004,  101:  5455 
• 19 Leong P. Lautens M. J. Org. Chem.  2004,  69:  2194 
• 20 Lautens M. Dockendorff C. Org. Lett.  2003,  5:  3695 
• 21 Lautens M. Ma S. J. Org. Chem.  1996,  61:  7246 
• 22a For the Cu-catalyzed ring opening addition of Grignard reagents to 3-aza-2-oxabicyclo[2.2.1]hept-5-ene systems, see: Surman MD. Mulvihill MJ. Miller MJ. J. Org. Chem.  2002,  67:  4115 
• 22b

  On the other hand, some examples of Zr-catalyzed ring-opening addition of Grignard reagents to [3.2.1]oxabicycles are found in reference 8.

• 23 Nakamura M. Matsuo K. Inoue T. Nakamura E. Org. Lett.  2003,  5:  1373 
• For previous communications, see:
• 24a Gómez Arrayás R. Cabrera S. Carretero JC. Org. Lett.  2003,  5:  1333 
• 24b Gómez Arrayás R. Cabrera S. Carretero JC. Org. Lett.  2005,  7:  219 
• 25 Recently, the enantioselective variant of this reaction has been reported using Cu(OTf)₂ in combination with a phosphoramidite ligand as catalyst: Zhang W. Wang L.-X. Shi W.-J. Zhou Q.-L. J. Org. Chem.  2005,  70:  3734 
• 26 For a previous synthesis of syn-2b, see reference 6. For a previous synthesis of anti-2b, see ref. 16 and: Bertozzi F. Crotti P. Del Moro F. Feringa BL. Chem. Commun.  2001,  24:  2606 
• 28 Allred GD. Liebeskind LS. J. Am. Chem. Soc.  1996,  118:  2748 
• 29 For the use of CuTC in copper-catalyzed S_N2′ addition of Grignard reagents to allylic chlorides, see: Alexakis A. Croset K. Org. Lett.  2002,  4:  4147 
• For previous synthesis of anti-2a, see ref. 16 and:
• 33a Jeffrey AM. Jerina DM. J. Am. Chem. Soc.  1975,  97:  4427 
• 33b Tsang WS. Griffing GW. Horning MG. Stillwell WG. J. Org. Chem.  1982,  47:  5339 
• These substrates were prepared by Diels-Alder cyclo­-addition of furan with substituted benzyne intermediates:
• 34a 1d: Jung ME. Lam PY.-S. Mansuri MM. Spelt LM. J. Org. Chem.  1985,  50:  1087 
• 34b 1b: Caster KC. Keck CG. Walls RD. J. Org. Chem.  2001,  66:  2932 
• 34c 1c: Giles RGF. Hughes AB. Sargent MV. J. Chem. Soc., Perkin Trans. 1  1991,  1581 
• 35 For previous synthesis of 10 via ring-opening addition of silyl nucleophiles to 8, see: Lautens M. Ma S. Belter RK. Chiu P. Leschziner A. J. Org. Chem.  1992,  57:  4065 
• For the synthesis of 11, see:
• 36a Mirsadeghi S. Rickborn B. J. Org. Chem.  1986,  51:  986 
• 36b Kawabata H. Nishino T. Nishiyama Y. Sonoda N. Tetrahedron Lett.  2002,  43:  4911 
• 36c

  For previous ring opening of substrate 11, see reference 16.

• 37 CH₂Cl₂ was used because of the low solubility of sulfon­-amides 13 and 15-17 in toluene. 1,2-Dichloroethane provided results similar to those of CH₂Cl₂
• For other successful applications of the (2-pyridyl)sulfonyl group in transition-metal-catalyzed reactions, see:
• 38a Llamas T. Gómez Arrayás R. Carretero JC. Adv. Synth. Catal.  2004,  346:  1651 
• 38b Mauleón P. Carretero JC. Org. Lett.  2004,  6:  3195 
• 38c Han H. Bae I. Yoo EJ. Lee J. Do Y. Chang S. Org. Lett.  2004,  6:  4109 
• 38d Esquivias J. Gómez Arrayás R. Carretero JC. J. Org. Chem.  2005,  70:  7451 
• 38e Mauleón P. Carretero JC. Chem. Commun.  2005,  4961 
• 38f Esquivias J. Gómez Arrayás R. Carretero JC. Angew. Chem. Int. Ed.  2006,  45:  629 
• 38g Sugimoto H. Nakamura S. Hattori M. Ozeki S. Shibata N. Toru T. Tetrahedron Lett.  2005,  46:  8941 
• 39 Pak CS. Lim DS. Synth. Commun.  2001,  31:  2209 
• 40 Vaccaro W. Amore C. Berger J. Burrier R. Clader J. Davis H. Domalski M. Fevig T. Salisbury B. Sher R. J. Med. Chem.  1996,  39:  1704 
• It is known that, after an initial π-complexation of Cu^I to the double bond and subsequent S_N2′ oxidative addition, the resulting (σ-allyl)-Cu^III complex can undergo a fast reductive elimination prior to isomerization:
• 42a Sofia A. Karlstrom E. Bäckvall J.-E. Chem. Eur. J.  2001,  7:  1981;  and references cited therein
• For the formation of (σ-allyl)copper intermediates leading to anti S_N2′ products in alkylation of allylic substrates, see:
• 42b Bertz SH. Chopra A. Eriksson M. Ogle CA. Seagle P. Chem. Eur. J.  1999,  5:  2680 
• 42c Ito M. Matsuumi M. Murugesh MG. Kobayashi Y. J. Org. Chem.  2001,  66:  5881 
• It has been reported that the combination of an organocopper reagent and a Lewis acid greatly enhances the S_N2′ selectivity. For an excellent review on reaction mechanisms of organocuprate reagents in organic transformations, see:
• 43a Nakamura E. Mori S. Angew. Chem. Int. Ed.  2000,  39:  3750 
• 43b See also: Karlström ASE. Bäckvall J.-E. In Modern Organocopper Chemistry   Krause N. Wiley-VCH; Weinheim: 2002.  p.259 
• 43c See also: Breit B. Demel P. In Modern Organocopper Chemistry   Krause N. Wiley-VCH; Weinheim: 2002.  p.188-223  
• 45 Diltz S. Aguirre G. Ortega F. Walsh P. Tetrahedron: Asymmetry  1997,  21:  3559 

5

Results communicated within reference 1a (p 182).

27

Upon screening other commonly used ligands for copper such as dimethyl ethylenediamine, BINAP or bisoxazolines, it was found that the use of Ph₃P was crucial for achieving good yield and high anti selectivity.

30

Lower catalyst loading was also studied: the reaction of oxabenzonorbornadiene with EtMgBr in the presence of 5 mol% of CuCl and 5 mol% of Ph₃P provided anti-2b in lower yield due to the formation of 3 (8%) and 4 (7%) in the reaction mixture.

31

In the absence of Ph₃P, CuCl alone gave a 58:35:5 mixture of anti-2b, naphthalenol 3 and naphthalene (4), respectively, in the reaction of 1a with EtMgBr.

32

The anti stereochemistry of the ring-opened products was assigned by comparison of their NMR data with those of the reported compounds anti-2a, anti-2b (see ref. 26), and anti-9a and anti-9g (see ref. 21).

41

For a similar (π-allyl)copper pathway suggested in the anti-stereoselective addition of dialkylzinc reagents to oxabenzonorbornadienes, see reference 16.

44

In this direction, the copper(II)-catalyzed ring-opening reaction of 17 with Et₂Zn (1,2-dichloroethane, reflux), instead of EtMgBr, afforded exclusively the product syn-22b with only 20% conversion after 48 h (Figure [1] ), evidencing the key role exerted by the Grignard reagent in achieving both high reactivity and anti-stereocontrol.