A Route to Highly Functionalized β-Enaminoesters via a Domino Ring-Opening Cyclization/Decarboxylative Tautomerization Sequence of Donor–Acceptor Cyclopropanes with Substituted Malononitriles

Abstract

An unprecedented and domino synthetic strategy for the synthesis of highly functionalized carbocyclic β-enaminoesters bearing an all-carbon quaternary center via Yb(OTf)3-catalyzed ring-opening cyclization/decarboxylative tautomerization of donor-acceptor cyclopropanes with 2-alkyl malononitriles in excellent yields is described. The products are obtained as a single diastereomer in most cases where the nitrile and aryl groups are aligning in a cis orientation across the ring.

Carbocycles from donor–acceptor cyclopropanes

“…In an interesting follow up to this work, Ghorai showed a tandem ring-opening cyclization decarboxylation approach when substituted malononitriles 213 were employed (Scheme 53A). 68 The proposed mechanism suggests ring-opening of the cyclopropane by 216 followed by ring-closure to give intermediate 218. 69 Mechanistically, the reaction was presumed to go through two sequential insertion operations, initially to form an activated 2-iminocyclobutane (although no indications of this product were isolated during the reaction) followed by a second addition to give the desired cyclopentene product.…”

“…In an interesting follow up to this work, Ghorai showed a tandem ring-opening cyclization decarboxylation approach when substituted malononitriles 213 were employed (Scheme 53A). 68 The proposed mechanism suggests ringopening of the cyclopropane by 216 followed by ring-closure to give intermediate 218. This intermediate could undergo a facile demethoxycarbonylation to give 219, ultimately leading to the product 215 (Scheme 53B).…”

Lewis acid triggered N-alkylation of sulfoximines through nucleophilic ring-opening of donor–acceptor cyclopropanes: synthesis of γ-sulfoximino malonic diesters

“…All chemicals were purchased from Sigma-Aldrich and used without further purification. The D–A cyclopropanes 20 and sulfoximines 21 were prepared using known literature procedures.…”

Domino‐Ring Opening‐Cyclization (DROC) of Donor‐Acceptor (DA) Cyclopropanes

“…Quite contrary to our expectation, the reaction of DA cyclopropanes 3 with 2‐substituted malononitriles 4 , afforded carbocyclic β‐enaminoesters 7 as the sole product, instead of either 5 or 6 . Clearly, a domino‐ring opening‐cyclization‐decarboxylative‐tautomerization sequence occurred to provide these enaminoesters having an all‐carbon quaternary stereocenter, instead of the cyclopentanones 6 …”

“…We synthesized carbocyclic β‐enaminonitriles from the reaction of DA cyclopropanes with malononitriles via a DROC‐tautomerization sequence . Interestingly, when 2‐alkyl malononitriles were employed as the nucleophiles, carbocyclic β‐enaminoesters were produced via DROC, followed by a decarboxylative tautomerization step, due to unavailability of the acidic proton α to the nitrile functionality in the intermediate species …”