A Novel [3+2] Dipolar Cycloaddition Approach to Hexahydrobenzofuro[3,2-b]pyrroles

Abstract

A highly stereoselective intramolecular 1,3-dipolar cycloaddition reaction of azomethine ylides derived from 2-vinyloxybenzaldehydes proceeded smoothly to allow for a direct access to tricyclic hexahydrobenzofuro[3,2-b]pyrroles in good yields.

stereoselective synthesis - intramolecular reaction - 1,3-dipolar cycloadditions - azomethine ylides - 2-vinyloxybenzaldehydes - hexahydrobenzofuro[3,2-b]pyrroles

References and Notes

1 Kim I. Kim SG. Choi J. Lee GH. Tetrahedron  2008,  64:  664 

For chapters and reviews on 1,3-dipolar cycloadditions, see:

2a Carruthers W. Cycloaddition Reactions in Organic Synthesis   Pergamon Press; Oxford: 1990.  Chap. 6. p.269 

2b Padwa A. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Fleming I. Pergamon Press; New York: 1991.  p.1069 

2c Wade PA. In Comprehensive Organic Synthesis   Vol. 4:  Trost BM. Fleming I. Pergamon Press; New York: 1991.  p.1111 

2d Synthetic Applications of 1,3-Dipolar Cycloaddition Chemistry toward Heterocycles and Natural Products   Padwa A. Pearson W. Wiley and Sons; New York: 2003. 

2e Coldham I. Hufton R. Chem. Rev.  2005,  105:  2765 

2f Nair V. Suja TD. Tetrahedron  2007,  63:  12247 

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Spectral Data of 7a
^¹H NMR (300 MHz, CDCl₃): δ = 7.30-7.21 (m, 2 H), 6.93-6.82 (m, 2 H) 5.67 (dd, J = 7.8, 5.1 Hz, 1 H), 4.59 (d, J = 7.8 Hz, 1 H), 4.22 (q, J = 7.2 Hz, 2 H), 3.94 (d, J = 6.9 Hz, 1 H), 3.76 (s, 3 H), 3.52 (dd, J = 6.9, 5.1 Hz, 1 H), 2.56 (s, 3 H), 1.31 (t, J = 7.2 Hz, 3 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 170.8, 170.7, 160.1, 130.3, 126.8, 124.9, 121.0, 110.8, 87.8, 69.2, 68.1, 61.1, 54.8, 52.7, 36.3, 14.6. HRMS (EI): m/z calcd for [C₁₆H₁₉NO₅]⁺: 305.1263; found: 305.1265.

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CCDC 683322 contains the supplementary crystallographic data for compound 7a. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.

1,3-Dipolar cycloaddition reactions of azomethine ylides derived from 2-allyloxybenzaldehydes or 2-propargyloxy-benzaldehydes are well studied as compared to our present work. For selected examples, see:

5a Pospíšil J. Potáček M. Tetrahedron  2007,  63:  337 

5b Zhang W. Lu Y. Geib S. Org. Lett.  2005,  7:  2269 

5c Bashiardes G. Safir I. Barbot F. Laduranty J. Tetrahedron Lett.  2004,  45:  1567 

5d Bashiardes G. Safir I. Mohamad AS. Barbot F. Laduranty J. Org. Lett.  2003,  5:  4915 

5e Grigg R. Duffy LM. Dorrity MJ. Malone JF. Rajviroongit S. Thornton-Pett M. Tetrahedron  1990,  46:  2213 

5f Amornraksa K. Barr D. Donegan G. Grigg R. Ratananukul P. Sridharan V. Tetrahedron  1989,  45:  4649 

5g Kanemasa S. Sakamoto K. Tsuge O. Bull. Chem. Soc. Jpn.  1989,  62:  1960 

6 For a [3+2] cycloaddition of azomethine ylides derived from 2-allylbenzaldehyde, see: Carroll FI. Blough BE. Mascarella SW. Xu H. Goodman CB. Rothman RB. Med. Chem. Res.  1993,  3:  178 

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Yields were not optimized.