Fourth International Electronic Conference on Synthetic Organic Chemistry (ECSOC-4), www.mdpi.org/ecsoc-4.htm, September 1-30, 2000

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Enantioselective Intramolecular CH-Insertions upon Cu-Catalyzed Decomposition of Phenyliodonium Ylides
 

Paul Müller, Christelle Boléa
 

Department of Organic Chemistry, University of Geneva

30, Quai Ernest-Ansermet, CH-1211 Geneva 4, Switzerland

E-mail : [email protected]

Received: 18 July 2000 / Uploaded: 29 July 2000


 




Abstract.The Cu-catalyzed intramolecular CH insertion of phenyliodonium ylide 5b has been investigated at 0 °C in the presence     of several chiral ligands. Enantioselectivities  vary  in  the range of 38�72 %, and are higher than those resulting from reaction of  the    diazo  compound  5c  at  65 °C. The  results  are  consistent  with  a  carbenoid   mechanism  for  Cu-catalyzed   decomposition  of   phenyliodonium ylides.
 
 

Introduction

Phenyliodonium ylides are potential substitutes for diazo compounds in photochemical,1,2  thermal,1,3 and transition metal-catalyzed reactions.2-4 Although most of these reactions are believed to proceed via carbenes or metal carbenoids, the experimental support in favor of  the involvement of these intermediates is scarce.  Some years ago we presented evidence for metal carbenoid pathways in Rh(II)-catalyzed cyclopropanation and CH insertion reactions.5

The Cu(I) - catalyzed  decomposition  of  phenyliodonium   ylides in  the presence of olefins affords cyclopropanes.  A mechanism involving   electrophilic  addition  of  the iodonium center to the double bond followed by reductive elimination of PhI, as shown in Scheme 1 has been proposed for this transformation. A carbene or metal carbenoid mechanism was specifically ruled out.6
 


Scheme 1
 


Recently we reported the intramolecular cyclopropanation of phenyliodonium ylides derived from acetoacetates and malonates with [Cu(OTf)2] in the presence of chiral ligands. Thus, the reaction of ylide 1a afforded 2 with the binaphtalene derived oxazoline A as ligand in 48 % yield and with 68 % ee (Scheme 2).7
 


Scheme 2
 

This result is inconsistent with the mechanism proposed by Moriarty. If the reaction proceeds via electrophilic attack of the iodonium center  on the  double bond,  the metal is not involved in the reaction and,  therefore,  no asymmetric induction should occur.  On the other hand,  if a carbenoid mechanism  applies, the  enantioselectivity  resulting  upon  decomposition of 1a should be identical to that obtained with the corresponding diazo compound 1b provided the same chiral ligand is used. Conclusive evidence for metal carbenoid intermediates upon Cu-catalyzed decomposition of diazo compounds has been reported.8 Unfortunately,the conventionally used chiral Cu-catalysts proved to be insufficiently reactive for decomposition of 1b or of similar diazocompounds derived from b-ketoesters and other 1, 3-dicarbonyl compounds  under  conditions  suitable for reaction of phenyliodonium ylides. Typically, the ylide 3a underwent intramolecular cyclopropanation with  [Cu(OTf)2 and  ligand  A  in  CH2Cl2  at  0 °C  to  provide  4  in  34 % yield and 30 % ee, but decomposition  of  the  corresponding  diazo  compound 3b required heating in trifluorotoluene at 100 °C. In general enantioselectivity increases  with  decreasing  temperature  and,  therefore,  a  higher enantioselectivity for the reaction of 3a was expected. Surprisingly, however,  the  product  4  resulting  from diazo decomposition of 3b had a higher enantiomeric excess (72 % ee, 51 % yield) than that resulting from 3a. The  intramolecular  cyclopropanation  of  3a  and  3b  in  the  presence of other chiral ligands revealed remarkable inconsistencies.  With  some  ligands  the  enantioselectivity  observed  upon  reaction  of  the  ylide  was  higher  than that from diazo decomposition, and  with  others  the  trend was inversed. These discrepancies suggest that the cyclopropanation with phenyliodonium
ylide may not entirely proceed via a metal carbenoid, but also via some other, uncatalyzed pathway as suggested by Moriarty. Indeed, uncatalyzed intramolecular cyclopropanations of phenyliodonium ylides have been observed previously.5,6

The mechanism of Moriarty for uncatalyzed cyclopropanations with phenyliodonium ylides is plausible, but this mechanism should not apply to uncatalyzed CH bond insertions. Indeed,  no  insertion products upon uncatalyzed decomposition of phenyliodonium ylides at ambient temperatures have ever been observed or reported. The phenyliodonium ylide derived from diethylmalonate does indeed insert into the CH bonds of cyclohexane, but this reaction requires a temperature of 100 °C, and it is believed to proceed via a free carbene.1 We  reasoned  that  comparison  of   enantioselectivities  in  CH  bond  insertions   resulting  from   Cu - catalyzed  decompositions  of phenyliodonium ylides and of the corresponding diazo compounds, respectively, would not be affected by the irregularities occurring in cyclopropanations, and would, therefore, allow more meaningful conclusions on the reaction mechanism.
 
 

Results and Discussion

The phenyliodonium ylide 5b was  synthesized  by reaction of the  hydrocarbon 5a9 with PhI(OAc)2.10 Exposure of 5b to [Cu(OTf)2 in CH2Cl2 at  0 °C  in  the  presence  of chiral ligands B � E resulted in  intramolecular CH insertion and afforded the cyclopentanone carboxylate 6. The enantioselectivity of the reaction was established on the ketone 7 (g. c., DAICEL, Lipodex B), which was obtained via ester hydrolysis of 6 (HBr / EtOH)  and  subsequent  decarboxylation  of  the  intermediate b-ketoacid. Reactions  with  the diazo  compound 5c were carried out in 1,2-dichloroethane at 65 °C. The results are summarized in Table 1.
 


Scheme 3
 


In general, we find that the Cu-catalyzed insertions proceed with acceptable yields from the ylide. The occurrence of CH insertions upon  catalysis  with  Cu  is  remarkable  in  itself,  since  it  is  well  known,  that  Cu-catalysts  are  the   catalysts  of   choice  for cyclopropanations. However, this preference is only significant when cyclopropanation and insertion pathways are competitive, and this  is  not  the  case  with  5b  and 5c. Other Cu-catalyzed CH insertions of diazocompounds have been reported.11 The yields of insertion  product  6 resulting from the reaction of the ylide 5bare generally higher than those of the diazo decomposition. This is a consequence of the notorious low reactivity of diazo esters and diazo ketones derived from b-dicarbonyl compounds, which require temperatures  of  up  to  80 °C  with Cu-catalysts and with dirhodium(II)-carboxamidates.12 Phenyliodonium ylides are significantly more reactive  and  may  be  decomposed  already  at 0 °C with Cu-catalysts or Rh(II)-carboxamidates. This enhanced reactivity in comparison of that of diazo compounds constitutes the main aspect of interest of phenyliodonium ylides.
 


Ligands
 



Table 1. Yields and enantioselectivities in intramolecular CH insertions of phenyliodonium ylide 5b and diazo ketoester 5c
 
 
 

Entry
Ligand
Yield from 5b (%)
ee from 5b (%)
Yield from 5c (%)
ee from 5c (%)
1
B
47
67
17
51
2
C
46
59
35
60
3
D
52
72
14
31
4
E
51
42
38
15
5
F
49
38
32
18

The enantioselectivity  resulting from  ylide decomposition is with all ligands higher than that from diazo decomposition. This trend was to be expected  on the grounds of the  different temperatures of the reactions. In addition, catalyst stability becomes a problem at elevated temperatures, and the low ee�s observed in some of the  reactions may be due to partial degradation of the catalyst. The intriguing irregularities in the enantioselectivities of Cu-catalyzed cyclopropanations of phenyliodonium ylides and diazo compounds do clearly not occur in the CH insertion reactions. These  observations  are  not  only  of  mechanistic interest; they also extend the synthetic potential of phenyliodonium ylides.
 
 

Conclusion

To our knowledge,these are the first enantioselective CH insertions observed upon Cu-catalyzed decompositions of phenyliodonium ylides. The results show  clearly  that  the  reactions  proceed  in  the  intimate vicinity of the chiral catalyst, and that the mechanism   proposed by Moriarty  for  cyclopropanations  cannot  apply to the CH insertions. A carbenoid  mechanism is generally accepted for CH insertions resulting from transition metal-catalyzed diazo decomposition, and the same mechanism should apply to the reaction of phenyliodonium ylides. This mechanism requires retention of configuration at the center undergoing insertion. Verification of the stereochemistry of the Cu-catalyzed CH insertion of phenyliodonium ylides is currently in progress in this laboratory.
 
 

Acknowledgements.
This work was supported by the Swiss National Science Foundation (Grant Nos. 20-52581.97 and 2027-048156) and by the European Commission for Science, Research and Development (COST Action D12).
 
 

References

[1] M. B. Camach, A. E. Clark, T. A. Liebrecht, J. P. DeLuca, J. Am. Chem. Soc. 2000, 122, 5210.

[2] Y. Hayasi, T. Okada, M. Kawanisi, Bull. Chem. Soc. Jpn. 1970, 43, 2506.

[3] L. Hadjiarapoglou, A. Varvoglis, N. W. Alcock, G. A. Pike, J. Chem. Soc. Perkin Trans. 1 1988, 2839; L. Hadjiarapoglou, S. Spyroudis, A. Varvoglis, J. Am. Chem. Soc. 1985, 107, 7178; L. Hadjiarapoglou, Tetrahedron Lett. 1987, 28, 4449.

[4] (a) J. N. C. Hood, D. Loyd, W. A. McDonald, T. T. Shepherd, Tetrahedron 1982, 38, 3355. (b) T. Saito, K. Kikuchi, A. Kondo,      Synthesis 1995, 87; T. Saito, S. Gon, H. Kikuchi, S. Motoki, J. Chem. Res. (S) 1994, 2; J. Chem. Res. (M) 1994, 87. (c) D. J. Fairfax, D. J. Austin, S. L. Xu, A. Padwa, J. Chem. Soc. Perkin Trans. 1 1992, 2837.

[5] P. Müller, D. Fernandez, Helv. Chim. Acta 1995, 78, 947; P. Müller, D. Fernandez, P. Nury, J.-C. Rossier, J. Phys. Org. Chem.  1998, 11, 321.

[6] (a) R. M. Moriarty, O. Prakash, R. K. Vai, L. Zhao, J. Am. Chem. Soc. 1989, 111, 6443; R. M. Moriarty, O. Prakash, R. K. Vaid, L. Zhao, J. Am. Chem. Soc. 1990, 112, 1297; R. M. Moriarty, J. Kim, L. Guo, Tetrahedron Lett. 1993, 34, 4129; R. M. Moriarty, E. J. May, O. Prakash, Tetrahedron Lett. 1997, 38, 4333. (b) J. K. Gallos, T. V. Koftis, A. E. Kormbis, J. Chem. Soc. Perkin Trans. 1 1994, 611.

[7] P. Müller, C. Boléa, Synlett 2000, 826.

[8] M. P. Doyle, M. A. McKervey, Modern Catalytic Methods for Organic Synthesis with Diazo Compounds: From Cyclopropanes to Ylides; Wiley, New York, 1998, Chapter 2; M. P. Doyle, D. C. Forbes, Chem. Rev. 1998, 98, 911.

[9] S. Hashimoto, N. Watanabe, T. Sato, M. Shiro, S. Ikegami, Tetrahedron Lett. 1993, 3, 5109; S. Hashimoto, N. Watanabe, S. Ikegami, Synlett 1994, 353; S. Hasimoto, N. Watanabe, K. kawano, S. Ikegami, Synth. Commun. 1994, 24, 3277; N. Watanabe, M. Anada, S. Hashimoto, S. Ikegami, Synlett. 1994, 1031.

[10] K. Schank, C. Lick, Synthesis 1983, 392.

[11] P. Müller, E. Maîtrejean, Collect. Czech. Chem. Commun. 1999, 64, 1807.

[12] M. P. Doyle, S. B. Davies, W. Hu, Org. Lett. 2000, 2, 1145.
 

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