A novel synthesis of flav-3-enes by claisen rearrangement

The Mitsunobu Reaction

Abstract: Alkyl and aryl phosphites and phosphines react with compounds having weak heteroatom–heteroatom bonds, such as SS, OO, etc., and with azo compounds to form reactive phosphonium salts. These phosphonium salts in turn promote “redox” condensation reactions with compounds having active hydrogens. The condensation reaction of alcohols using the redox couple of a triaryl- or trialkylphosphine and a dialkyl azodicarboxylate has become known as the Mitsunobu reaction, based on his pioneering work in the late 1960s. The overall reaction is summarized, wherein the alcohol (R1OH) and acidic compound (H–Nu) are condensed to form product (R1–Nu), while triphenylphosphine is oxidized to triphenylphosphine oxide and the azodicarboxylate is reduced to the hydrazine. Although the typical redox combination is diethyl azodicarboxylate (DEAD) and triphenylphosphine, many other combinations have found selected use. The reaction is generally limited to primary and secondary alcohols, although tertiary alcohols react in a few intramolecular and intermolecular reactions. For secondary alcohols the reaction usually proceeds with clean inversion of stereochemistry. The acidic component of the reaction generally has an aqueous pKa < 15, with intramolecular reactions providing the exceptions. Examples of H–Nu include oxygen nucleophiles such as carboxylic acids and phenols; nitrogen nucleophiles such as imides, hydroxamates, and heterocycles; sulfur nucleophiles such as thiols and thioamides; and carbon nucleophiles such as β-ketoesters. Major reviews of the Mitsunobu reaction were published in 1981 by Mitsunobu and in 1983 by Castro. The former review concentrated on reactions using DEAD/triphenylphosphine, while the latter review focused on reactions in which halogens replaced the hydroxy group using reagents such as triphenylphosphine/carbon tetrachloride, triphenyl phosphite/iodomethane, and triphenylphosphine/N-halosuccinimide. Reactions involving the DEAD/triphenylphosphine redox system are the principal subject of this chapter, with emphasis on the literature between 1981 and 1988. Keywords: Mitsunobu reaction; adduct formation; alcohol activation; SN2 reaction; mechanisms; carbon–oxygen bond; carbon–nitrogen bond; carbon–sulfur bond; carbon–halogen bond; carbon–carbon bond; ambident nucleophiles; dehydration; alkenes; method comparison; ester formation; lactone formation; akyl aryl ether; epoxides; dialkyl ethers; enol ethers; dialkyl ethers; imides; azides; experimental procedures; scope; limitations

7.2 – Claisen Rearrangements

Abstract: This article surveys variants of the Claisen rearrangement that are of general use in stereoselective organic synthesis. Recent results concerning the influence of steric and electronic parameters on transition state geometries are highlighted. The impact of the Claisen methodology in modern synthetic strategy and its application for the preparation of highly functionalized derivatives is exemplified.

Iridium‐Catalyzed Asymmetric Allylic Etherification and Ring‐Closing Metathesis Reaction for Enantioselective Synthesis of Chromene and 2,5‐Dihydrobenzo[b]oxepine Derivatives

Abstract: Iridium-catalyzed asymmetric etherifications of allylic carbonates with 2-vinylphenols and 2-allylphenols were realized. With a catalyst generated from 2 mol% of [Ir(cod)Cl]2 (cod=cycloocta-1,5-diene) and 4 mol% of the phosphoramidite ligand L2, the etherification products were obtained in excellent ees and then subjected to the ring-closing metathesis reaction providing an efficient synthesis of enantioenriched 2H-chromene and 2,5-dihydrobenzo[b]oxepine derivatives.

Time-Resolved Absorption Studies on the Photochromic Process of 2H-Benzopyrans in the Picosecond to Submillisecond Time Domain

Abstract: Picosecond to submillisecond photochromic reactions of 2,4-diphenyl-2H-benzopyran and 2,2,4-triphenyl-2H-benzopyran have been investigated by time-resolved absorption spectroscopy. The C−O bond cleavage of the benzopyrans (closed forms) occurs via the first excited singlet state within 2 ps to produce vibrationally excited open forms in the ground electronic state. In the subnanosecond to submillisecond time domain, several decay components with almost the same spectral profiles are observed. These components are assigned to respective stereoisomers with respect to two double bonds and one single bond of the open enone forms. From the pump-laser power dependencies of the yields of the open forms, it is suggested that the photocleavage gives at first only the open forms revertible to the closed form by a single-bond rotation, and that the photoexcitation of the first generated open forms gives rise to other open forms which need a double-bond rotation for reversion to the closed form. The photochromic reac...

Sigmatropische Umlagerungen von Aryl‐propargyläthern; Synthese von 1, 5‐Dimethyl‐6‐methylen‐tricyclo[3, 2, 1, 02,7]‐oct‐3‐en‐8‐on‐Derivaten. Vorläufige Mitteilung

Abstract: 2, 6-Dimethylphenyl propargyl ether (10) and its derivatives 12–15 rearrange thermally to 1, 5-dimethyl-6-methylene-tricyclo [3.2.1.02,7]oct-3-en-8-one (9) and related compounds 16–19. The ethers undergo first an aromatic [3, 3]-sigmatropic rearrangement to ortho-allenyldienones 11, which then undergo ring closure to the tricyclic products by an electrocyclic reaction. Only in the case of the γ-methylpropargyl ether 13, the ortho-dienone 11 is further rearranged in low yield to the para-butynylphenol 20, but the tricyclic ketone 17 is again the main product. New data show that the known thermal cyclisation of aryl propargyl ethers to chromenes (e. g. 4 8) involves a preliminary [3, 3]-sigmatropic rearrangement.

Studies on Acetylenic Compounds. XXXII. Ring Closure of Propargyl Ethers. (2).

Abstract: This is a new synthetic method for various 4-substituted-3-chromenes : phenyl propargyl ethers underwent intramolecular cyclization to give 4-chromene derivatives by heating with diethylaniline. The reaction mechanism was clarified by the study of substituted phenyl propargyl ethers under the consideration of their electronic effects on the yields of resulting 3-chromene ; in general, the presence of +R group enhanced the cyclization, whereas -R group gave much lower yields of the corresponding chromenes. Therefore, this intramolecular cyclization is concluded to be an electrophilic reaction.

Claisen rearrangement of aryl propargyl ethers in poly(ethylene glycol)- a remarkable substituent and solvent effect

Abstract: The Claisen rearrangement of aryl propargyl ethers in poly(ethylene glycol) - 200 at 200°C affords products in good yields. Aryl propargyl ethers containing electron donating groups yield (2H)-benzopyrans and those containing electron withdrawing groups yield 2-methylbenzofurans.

Flavan derivatives. XXIII. Preparation and synthetic applications of Flav-3-enes

Abstract: 2'-Hydroxychalcones and α-alkoxy-2'-hydroxychalcones are converted by sodium borohydride in isopropanol into flav-3-enes and 3-alkoxyflav-3-enes in the convenient new synthesis which makes these flavenes readily available. Catalytic reduction of the flavenes gives the corresponding flavans or 3-alkoxyflavans in high yield, and the latter are obtained mainly in the 2,s-cis-form. The flavenes immediately give flavs lium cations in the cold when treated with acids in air, and oxidation of 5,7,3',4'-tetramethoxyflav-3-ene with benzoquinone in an acidic medium gave the flavylium salt, isolated as the ferrichloride. Reduction of 5,7,3',4'-tetramethoxy-flavylium chloride with lithium aluminium hydride gave 5,7,3',4'-tetramethoxy-flav-2-ene identical with the flavene obtained from (-)-epicatechin tetramethyl ether, and confirms an earlier investigation by Gramshaw, Johnson, and King. In its N.M.R. spectrum the heterocyclic-ring protons of this flav-2-ene give an ABX multiplet which is easily distinguished from the ABX multiplet at much lower field characteristic of flav-3-enes.