posted on 2024-03-18, 13:04authored byJin Su Ham, Mina Son, Christina G. Na, Bohyun Park, Mu-Hyun Baik, Richmond Sarpong
Herein, we describe the synthesis of substituted oxepane
derivatives
through the skeletal remodeling of 4-hydroxy-2-cyclobutenones, which
are readily prepared from commercially available dialkyl squarates
upon their reaction with acrylonitrile. Mechanistically, a Rh(I)-catalyzed
C–C bond formation and cleavage cascade is proposed. Specifically,
a fused [3.2.0] bicycle is proposed to form from dialkyl squarate-derived
cyclobutenols via an unusual Rh(I)-catalyzed intermolecular oxa-Michael
addition of a tertiary alcohol with acrylonitrile, followed by an
intramolecular conjugate addition/migratory insertion. Subsequent
C(sp3)–C(sp3) bond cleavage through a
Rh-catalyzed β-carbon elimination is then theorized to furnish
the oxepane scaffold. Computational studies support the formation
of an intermediate [3.2.0] bicycle but also point to an alternative
pathway for the formation of the oxepane products involving a Rh(III)
intermediate. Additional studies have shown the overall process to
be stereoretentive. The functional groups that are introduced in this
process can be leveraged to form fused or bridged ring systems.