Grignard Reagent Acceleration of the Intramolecular Diels–Alder Reaction of Furans with Unactivated Alkynes: Towards Structurally Complex Oxabicyclic Alkenes

Abstract

A systematic methodology for the design and verification of chemical‐based products is proposed. By integrating modeling, and experiments, the search space is efficiently scanned to identify the feasible product candidates. The product design (or verification) problem consists of three stages: computer‐aided design (Stage 1), which generates a list of feasible candidates, experimental planning (Stage 2), which generates a list of experiments and checks the available experimental set‐ups, and experimental testing (Stage 3), which measures the necessary data and verifies the desirable attributes of the final product. The first stage (Stage 1) has been covered in previous publications, along with detailed case studies. The development of Stage 2 and Stage 3 is considered in this article and highlighted through two case studies involving the design and validation of an insect repellent lotion and a sunscreen lotion. © 2011 American Institute of Chemical Engineers AIChE J, 2012

Gold-Catalyzed Furan/Yne Cyclizations for the Regiodefined Assembly of Multisubstituted Protected 1-Naphthols

“…On the basis of these results, we hypothesized that 2-furylcarbinol derivatives bearing an ( o -alkynyl)phenyl moiety would be effective for the general synthesis of functionalized naphthols via gold-catalyzed reaction (Scheme ). In this design, the furan moiety could be easily introduced through nucleophilic addition of 2-furanyllithium to an aldehyde . Herein, we report our success in gold-catalyzed cycloisomerization of furan/ynes 1 to highly functionalized 1-naphthols 2 protected with a TBS group with high ( Z )-stereoselectivity.…”

“…The requisite substrates of TBS-protected ( o -alkynyl)phenyl 2-furylcarbinols 1 could be easily prepared in good to high yields through addition of the corresponding furanyllithium reagents to ( o -alkynyl)benzaldehydes followed by ether formation with TBSCl. Compound 1a was selected as a model substrate to probe the feasibility of the intramolecular furan/yne cyclization reaction.…”

Organo-Catalyzed Asymmetric Michael–Hemiketalization–Oxa-Pictet–Spengler Cyclization for Bridged and Spiro Heterocyclic Skeletons: Oxocarbenium Ion as a Key Intermediate

“…Among them, the synthesis of bridged or spiro heterocycles that possess all quaternary carbon centers is always a challenging research area . It has been primarily addressed by nucleophilic addition, photoinduced electron transfer, intramolecular Baylis–Hillman reaction, Diels–Alder reaction, cycloadditions and condensations, rearrangement, dearomatization, as well as multicomponent and domino reactions . Despite the myriad approaches afforded by these reactions, few synthetic methods that produce bridged and spiro heterocycles structures were developed by using acyclic precursors.…”

Gold(I)‐Catalyzed 1,4‐ and/or 1,5‐Heteroaryl Migration Reactions through Regiocontrolled Cyclizations

“…The requisite substrates of TMS-protected (o-alkynyl)phenyl (2-furyl)carbinols 1 were easily accessible through addition of furanyllithium reagents to o-(alkynyl)phenyl ketones, or addition of the corresponding Grignard reagents to o-(alkynyl)-phenyl furanyl ketones, [9] followed by protection with TMSCl. We chose furan-yne 1 a as a model substrate to explore the new reaction pathways.…”