Hydrogen Bond Controlled Anti-Aza-Michael Addition: Diastereoselective Synthesis of Cyclobutene-Containing Amino Acid Derivatives
The chemical reactivity encoded in a highly substituted cyclobutane platform, which contains the (E,E)-dimethyl 2,2'-(cyclobutane-1,2-diylidene)diacetate structural motif, has been explored. The cyclobutane platform features a C2 axis of symmetry as well as a dense and interconnected ring functionalization pattern that is defined by two allylic/benzylic stereogenic oxygen-containing quaternary centers with a 1,2-trans configuration and two exocyclic acrylate chains. The reactivity profile of the cyclobutane platform is defined by two important kinetic barriers (steric strain and antiaromaticity) and two structure-biased chemical processes: (1) the thermally-driven [3,3] sigmatropic rearrangement between one of the two equivalent aryloates and the corresponding allylic acrylate chain and (2) the allylic nucleophilic substitution (SN2' reaction) that involves a tertiary aryloate and its exocyclic double bond (anti-Michael addition). The reaction of platform 3a with secondary amines delivered the corresponding cyclobutene amino acid derivatives 15a¿15f in excellent yields (up to ¿95¿%) and high diastereoselectivities (up to 99:1). Computational studies are described to rationalize the observed diastereoselectivity.
| Main Authors: | , , , , |
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| Other Authors: | |
| Format: | artículo biblioteca |
| Published: |
Wiley-VCH
2015-06
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| Subjects: | Hydrogen bonds, Diastereoselectivity, Sigmatropic rearrangement, Michael addition, Amino acids, |
| Online Access: | http://hdl.handle.net/10261/132392 http://dx.doi.org/10.13039/501100000780 http://dx.doi.org/10.13039/501100003329 |
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| Summary: | The chemical reactivity encoded in a highly substituted cyclobutane platform, which contains the (E,E)-dimethyl 2,2'-(cyclobutane-1,2-diylidene)diacetate structural motif, has been explored. The cyclobutane platform features a C2 axis of symmetry as well as a dense and interconnected ring functionalization pattern that is defined by two allylic/benzylic stereogenic oxygen-containing quaternary centers with a 1,2-trans configuration and two exocyclic acrylate chains. The reactivity profile of the cyclobutane platform is defined by two important kinetic barriers (steric strain and antiaromaticity) and two structure-biased chemical processes: (1) the thermally-driven [3,3] sigmatropic rearrangement between one of the two equivalent aryloates and the corresponding allylic acrylate chain and (2) the allylic nucleophilic substitution (SN2' reaction) that involves a tertiary aryloate and its exocyclic double bond (anti-Michael addition). The reaction of platform 3a with secondary amines delivered the corresponding cyclobutene amino acid derivatives 15a¿15f in excellent yields (up to ¿95¿%) and high diastereoselectivities (up to 99:1). Computational studies are described to rationalize the observed diastereoselectivity. |
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