Synthesis of 1-Cyano-2-Methylenecyclopropane

The sample of (cyanomethylene)cyclopropane
(5) used in this work was prepared by the Wittig reaction
of 1-ethoxycyclopropanol and (cyanomethyl)triphenyl-phosphonium chloride,
as described previously.^{1 (link),3 (link)} The synthesis of 1-cyano-2-methylenecyclopropane
(7) followed the synthetic methodology that was first
developed for the synthesis of hypoglycin A, a natural product found
in unripe fruit from the Ackee tree.^{42 (link)} Carbon
et al. synthesized ethyl methylenecyclopropanecarboxylate by adding
ethyl diazoacetate to 2-bromopropene in the presence of a copper–bronze
catalyst followed by a sodium hydride-induced elimination (Scheme 2a).^{43 (link),44 (link)} Black and Landor utilized a zinc–copper-catalyzed reaction
to generate the methylenecyclopropane moiety in a much higher yield
(Scheme 2b).^{45 (link)} More recently, Lai and Liu improved the yield
of the ethyl diazoacetate route by utilizing a rhodium acetate catalyst
(Scheme 2c).^{46 (link)} Our synthesis of 7 closely follows
the established route of Lai and Liu.
Our synthesis of 1-cyano-2-methylenecyclopropane (7)
is presented in Scheme 3.⁴⁷ The sequence begins with a
rhodium acetate-catalyzed cyclopropanation reaction of 2-bromopropene
with ethyl diazoacetate using a procedure modified from Scott et al.,^{48 (link)} followed by a sodium hydride-induced elimination
of bromide from 9 to generate the methylenecyclopropane
moiety. Ester 10 is converted to amide 11(49 (link)) and then treated with phosphoric anhydride
to produce nitrile 7 through dehydration of 11.