Ethoxy vinyl ether cycloaddition

The most comprehensive examination of the Rokita kinetic procedure from a synthetic standpoint was carried out by Barrero and coworkers.6 They examined the effects of various leaving groups, solvents, nucleophiles, and their equivalents on subsequent [4 + 2] cycloadditions. Avast excess of the intended nucleophile (50-100 equiv) must be employed, because the fluoride triggered (3-elimination proves nearly instantaneous at room temperature resulting in a high concentration of a species that is prone to undergo dimerization and other undesired side reactions that are irreversible at these low temperatures (Fig. 4.7). Use of fewer equivalents of the intended nucleophile led to a rapid drop off in yield. For example, 5-10 equivalents of ethoxy vinyl ether (EVE) affords only a 5-10% yield of the desired benzopyran... 

However, most asymmetric 1,3-dipolar cycloaddition reactions of nitrile oxides with alkenes are carried out without Lewis acids as catalysts using either chiral alkenes or chiral auxiliary compounds (with achiral alkenes). Diverse chiral alkenes are in use, such as camphor-derived chiral N-acryloylhydrazide (195), C2-symmetric l,3-diacryloyl-2,2-dimethyl-4,5-diphenylimidazolidine, chiral 3-acryloyl-2,2-dimethyl-4-phenyloxazolidine (196, 197), sugar-based ethenyl ethers (198), acrylic esters (199, 200), C-bonded vinyl-substituted sugar (201), chirally modified vinylboronic ester derived from D-( + )-mannitol (202), (l/ )-menthyl vinyl ether (203), chiral derivatives of vinylacetic acid (204), ( )-l-ethoxy-3-fluoroalkyl-3-hydroxy-4-(4-methylphenylsulfinyl)but-1 -enes (205), enantiopure Y-oxygenated-a,P-unsaturated phenyl sulfones (206), chiral (a-oxyallyl)silanes (207), and (S )-but-3-ene-1,2-diol derivatives (208). As a chiral auxiliary, diisopropyl (i ,i )-tartrate (209, 210) has been very popular. 

A peroxy acid mediated oxidative rearrangement of 2-alkoxy-3,4-dihydro-2//- pyrans affords 5-alkoxytetrahydrofuran-2-carbaldehydes (79JCS(Pi)847>. This reaction pathway was used in developing a method for the synthesis of optically active monoalkylfurans. (S)-2-Ethoxy-5-s-butyl-3,4-dihydro-2//-pyran (319), obtained through a cycloaddition reaction of (S)-2-s-butylacrolein to ethyl vinyl ether, was converted to (S)-2-s-butyl-5-ethoxytetrahydrofuran-2-carbaldehyde (320) (Scheme 85). 

Using a Zincke-Bradsher convergent strategy for the synthesis of the ABE tricyclic core of Manzamine A, Magnier and Langlois reported the use of aqueous conditions to achieve, in one pot, the preparation of a naphthylpyridi-nium salt intermediate which underwent an inverse electron demand heterocyclic Diels-Alder cycloaddition with either ethyl vinyl ether or (Z)-l-ethoxy-... 

The reaction of several a-diazoketones with ethyl vinyl ether under various conditions has been examined. In the presence of metal salts [Rh2(OAc)4, Pd(OAc)2, CuCl] ethoxy dihydrofurans are produced. The initial product of this reaction sequence is a cyclopropyl ketone which suffers from a spontaneous rearrangement to the dihydrofuran <96CJC2401>. An efficient synthesis of 3-acylfurans is achieved by Ag(I)/Celite mediated cycloaddition of dicarbonyl compounds with vinyl sulfide (<97TL5671> see also <97TL2095>). A two-step synthesis of 2-substituted 4-furanmethanol compounds was reported. The method involves a Homer-Wadsworth-Emmons reaction between 3-ketophosphonates and l,3-diacetoxy-2-... 

Arynes react readily with simple alkenes to give either benzocyclobutenes or substituted benzenes (Scheme 7.31). The formation of benzocyclobutenes by [2+2] cycloaddition reaction of the aryne to the alkene proceeds best for strained and electron-rich carbon-carbon (C=C) double bonds. For example, dicyclopentadiene reacts to give the ex o-isomer of the corresponding four-membered ring in good yield. The addition to cyanoethene (acrylonitrile) and the reaction with the electron-rich ethoxyethene (ethyl vinyl ether) gives the cyano- and ethoxy-benzocyclobutenes in 20% and 40% yields, respectively. The latter reaction almost certainly involves nucleophilic addition of the enol ether to the electrophilic aryne followed by coUapse... 

AT-Sulphinyltoluene-p-sulphonamide underwent reversible cycloaddition to ethyl vinyl ether at — 30 °C to give an approximately equiraolecular mixture of iV-toluene-p-sulphonyl-3-ethoxy-1,2-thiazetidine cis- and trans-1-oxides (128) and (129), the /ra/w-oxide (129) reverting to starting materials at 0 °C whilst the cw-isomer (128) did so above room temperature. Phenyl vinyl ether gave (130) and (131) slowly at 24 °C these oxides, which were formed in the ratio 2.5 to 1, did not revert to starting materials. The adducts (132)—(135) formed from cis- and trans-ra ihy 1-hexenyl ether... 

However, 4 does not look like the expected cycloaddition adduct between 1 and ethyl vinyl ether. In fact, the expected [4+2] adduct should be more like bicyclic product 5, with four nitrogen atoms in a six-membered ring and an ethoxy group incorporated somewhere in the structure. We could then consider that, if 5 has been formed at first instance, some further transformations of this product have arisen after the cycloaddition step. 

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