An amido cuprate formed from CuCN and LDA allows a general deconjugative α-alkylation of cyclic alkenenitriles. Deprotonating cyclic alkenenitriles with LDA-CuCN avoids polymerization that otherwise plagues these alkylations and generates a reactive metalated nitrile for alkylations with a range of carbon and heteroatom electrophiles. The strategy provides an effective synthesis of quaternary 5-, 6-, and 7-membered cycloalk-1-enecarbonitriles substituted on the nitrile-bearing carbon.
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Cyclic Alkenenitriles: Copper-Catalyzed Deconjugative α-Alkylation.
J Org Chem
May 2016
Department of Chemistry, Drexel University, Philadelphia, Pennsylvania 19104, United States.
An amido cuprate formed from CuCN and LDA allows a general deconjugative α-alkylation of cyclic alkenenitriles. Deprotonating cyclic alkenenitriles with LDA-CuCN avoids polymerization that otherwise plagues these alkylations and generates a reactive metalated nitrile for alkylations with a range of carbon and heteroatom electrophiles. The strategy provides an effective synthesis of quaternary 5-, 6-, and 7-membered cycloalk-1-enecarbonitriles substituted on the nitrile-bearing carbon.
View Article and Find Full Text PDFAlkenenitriles: conjugate additions of alkyl iodides with a silica-supported zinc-copper matrix in water.
J Org Chem
August 2007
Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, Pennsylvania 15282-1530, USA.
A new silica-supported zinc-copper matrix reagent promotes the conjugate addition of alkyl iodides to cyclic and acyclic alkenenitriles in water. X-ray diffraction and electron microscopy techniques suggest that the active copper species generated from elemental zinc and copper(I) iodide is finely dispersed, zerovalent copper. Alkyl iodides react with the silica-supported reagent to generate putative radicaloid intermediates that efficiently add to alkenenitriles to provide beta-substituted nitriles.
View Article and Find Full Text PDFAlkenenitriles: Zn-Cu promoted conjugate additions of alkyl iodides in water.
Org Lett
April 2006
Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, Pennsylvania 15282-1530, USA.
[reaction: see text] A new silica-supported zinc-copper matrix dramatically promotes conjugate additions of alkyl iodides to alkenenitriles in water. Acyclic and cyclic nitriles react with functionalized alkyl iodides, overcoming the previous difficulty of performing conjugate additions to disubstituted alkenenitriles with nonstabilized carbon nucleophiles. Conjugate additions with omega-chloroalkyl iodides generate cyclic nitriles primed for cyclization, collectively providing one of the few annulation methods for cyclic alkenenitriles.
View Article and Find Full Text PDFCyclic alkenenitriles: synthesis, conjugate addition, and stereoselective annulation.
J Org Chem
October 2003
Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, Pennsylvania 15282-1530, USA.
O-Alkylation of unsaturated silyl cyanohydrins with DMSO-Ac2O triggers a rearrangement to methylthiomethyl-protected hydroxyalkenenitriles that are easily hydrolyzed for subsequent annulations with omega-chloroalkyl Grignard reagents. Deprotonating the gamma-hydroxyalkenenitriles with t-BuMgCl followed by addition of omega-chloroalkyl Grignard reagents triggers a conjugate addition-alkylation sequence leading exclusively to cis-octalins, hydrindanes, and decalins. Stereoelectronic control favors an axial conjugate addition leading to a particularly reactive conformer that rapidly cyclizes to cis-fused bicyclic nitriles, whereas generating the ring-flipped conformer, through a stepwise sequence, allows access to the diastereomeric trans-decalin.
View Article and Find Full Text PDFHydroxy alkenenitriles: diastereoselective conjugate addition-alkylations.
J Org Chem
May 2003
Department of Chemistry and Biochemistry, Duquesne University, Pittsburgh, Pennsylvania 15282-1530, USA.
Chelation-controlled conjugate addition of Grignard reagents to cyclic and acyclic gamma-hydroxyalkenenitriles stereoselectively generates beta-substituted hydroxynitriles. t-BuMgCl-induced deprotonation of gamma-hydroxyalkenenitriles followed by chloride-alkyl exchange from a second Grignard reagent, generates an alkylmagnesium alkoxide that triggers conjugate addition. Alkylation of the resulting magnesiated nitrile with alkyl halide and carbonyl electrophiles efficiently installs two new bonds and up to three stereocenters in a single synthetic operation.
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