Scheme 1. Diene-Transmissive Diels–Alder Cycloaddition Sequences of [3]- and [4]Dendralene with the Prototypical Olefinic Dienophile

The first synthesis of all five possible monomethylated [4]dendralenes has been achieved via two distinct synthetic strategies. The Diels–Alder chemistry of these new dendralenes (as multidienes) with an electron poor dienophile, N-methylmaleimide (NMM), has been studied. Thus, simply upon mixing the dendralene and an excess of dienophile at ambient temperature in a common solvent, sequences of cycloadditions result in the rapid generation of complex multicyclic products. Distinct product distributions are obtained with differently substituted dendralenes, demonstrating that dendralene substitution influences the pathway followed, when a matrix of mechanistic possibilities exists. Dendralene site selectivities are traced to electronic, steric and conformational effects, thereby allowing predictive tools for applications of substituted dendralenes in future synthetic endeavors.

Scheme 2. Diene-Transmissive Diels–Alder Cycloaddition Sequences of [4]Dendralene (1) with the Dienophile N-Methylmaleimide (NMM)

Scheme 3. Syntheses of the Five Mono-Methyl-Substituted-[4]Dendralenes

3 Diels-Alder reactions in 1 go

 
FROM https://naturalproductman.wordpress.com/2016/01/29/11137/

Tris-adduct 36

An analytic sample of 36 was obtained by recrystallization from EtOAc/hexane to give colorless needles, mp 255–257 °C; R_f 0.20 (EtOAc, 100%);  

 

¹H NMR (300 MHz, CDCl₃) δ 3.22 (dd, J = 8.6, 5.9 Hz, 1H), 3.19–3.07 (m, 3H), 3.04–2.91 (m, 5H), 2.90 (s, 6H), 2.86 (s, 3H), 2.65 (ddd, J = 14.1, 13.4, 5.4 Hz, 1H), 2.35 (ddd, J = 14.3, 5.0, 2.5 Hz, 1H), 2.16–2.05 (m, 2H), 2.03–1.91 (m, 1H), 1.85–1.74 (m, 1H), 1.54 (d, J = 6.8 Hz, 3H) ppm;  

 

¹³C NMR (75 MHz, CDCl₃) δ 179.7 (C), 178.5 (C), 178.4 (C), 178.3 (C), 177.0 (C), 176.6 (C), 130.8 (C), 130.8 (C), 44.4 (CH), 43.4 (CH), 40.8 (CH), 40.6 (CH), 40.3 (CH), 39.2 (CH), 38.8 (CH), 33.7 (CH), 29.0 (CH), 25.0 (CH₃), 24.9 (CH₃), 24.8 (CH₃), 24.7 (CH₂), 24.4 (CH₂), 23.1 (CH₂), 16.5 (CH₃) ppm; 

 

 

IR (KBr disc) ν_max = 2961, 2948, 2842, 1770, 1695, 1435, 1383, 1286 cm^–1; 

 

 

LRMS (70 eV, EI) m/z (%) 453 ([M]^+•, 100%), 438 (7), 342 (33), 256 (14), 112 (39); 

 

 

HRMS calc for C₂₄H₂₇N₃O₆ [M]^+• 453.1900, found 453.1905.

Synthesis and Diels–Alder Reactivity of Substituted [4]Dendralenes

Mehmet F. Saglam^†, Ali R. Alborzi^†, Alan D. Payne^†, Anthony C. Willis^†, Michael N. Paddon-Row^‡, and Michael S. Sherburn^*†

^† Research School of Chemistry, The Australian National University, Canberra, ACT 2601, Australia

^‡ School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia

J. Org. Chem., Article ASAP

DOI: 10.1021/acs.joc.5b02583

Publication Date (Web): January 12, 2016

Copyright © 2016 American Chemical Society

*E-mail: michael.sherburn@anu.edu.au.

 http://pubs.acs.org/doi/full/10.1021/acs.joc.5b02583

ACS Editors' Choice - This is an open access article published under an ACS AuthorChoice License, which permits copying and redistribution of the article or any adaptations for non-commercial purposes.

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