Cycloaddition to vinyl ether

Vinyl ethers undergo many cycloaddition reactions similar to those which take place with enamines. In general, however, these cycloaddition reactions with vinyl ethers take place less readily than those with enamines. These reactions include cycloaddition of vinyl ethers with ketene (200-205), phenyl isocyanate (206), sulfene (207,208), methyl acrylate (209), diethyl acetylenedicarboxylate (210), and diphenylnitrilimine (183). 

The 1,3-dipolar cycloaddition of nitrones to vinyl ethers is accelerated by Ti(IV) species. The efficiency of the catalyst depends on its complexation capacity. The use of Ti( PrO)2Cl2 favors the formation of trans cycloadducts, presumably, via an endo bidentate complex, in which the metal atom is simultaneously coordinated to the vinyl ether and to the cyclic nitrone or to the Z-isomer of the acyclic nitrones (800a). Highly diastereo- and enantioselective 1,3-dipolar cycloaddition reactions of nitrones with alkenes, catalyzed by chiral polybi-naphtyl Lewis acids, have been developed. Isoxazolidines with up to 99% ee were obtained. The chiral polymer ligand influences the stereoselectivity to the same extent as its monomeric version, but has the advantage of easy recovery and reuse (800b). 

Various substituted unsaturated acylphosphonates participate in highly dias-tereoselective and enantioselective cycloadditions with vinyl ethers, Eqs. 177 and 178. It is intriguing to note that catalysts [(.V,.Y)-f-Bu-box]Cu (OTf)2 (269c) and [(.V,.S )-Ph-box]Cu (OTf>2 (269d) possessing the same sense of chirality afford opposite antipodes of the cycloadduct in comparable selectivities. Cyclopentadiene was found to react with acylphosphonates to give a mixture of the normal Diels-Alder adduct and the inverse electron demand hetero-Diels-Alder adduct (35 65), Eq. 179. This result may be contrasted with crotonylimide, which furnishes the normal demand Diels-Alder adduct exclusively. 

A third mechanistically distinct [3 -1- 2] cycloaddition between vinyl ethers and vinyl-carbenoids was discovered and reported in 2001 [26]. This reaction is remarkable because when Rh2(S-DOSP)4 is used as the catalyst, the cis-cyclopentenes 142 are formed in up to 99% enantiomeric excess. The reaction occurs between vinylcarbenoids unsubstituted or alkyl-substituted at the vinyl terminus and vinyl ethers substituted with an aryl or vinyl group. Some illustrative examples are shown in Tab. 14.12. The reaction is considered to be a concerted process, which would be consistent with the highly stereoselective nature of the reaction [26]. Contrary to the [3-1-2] cycloaddition derived by means of vinylogous carbenoid reactivity, this latest [3 -1- 2] cycloaddition is not influenced by solvent effects. Due to steric demands on the carbenoid, the [3-1-2] cycloaddi-tion only occurs with cis-vinyl ethers. 

Most cycloadditions utilizing vinyl ethers to produce four-membered rings are stereospecific or at least stereoselective in relation to the vinyl ether. ... 

In a related case, the use of dioxazaborocines as the chiral auxiliary with benzonitrile oxide gave dipolar cycloadducts with a poor diastereomeric ratio dr 68 32) (195). Similarly, the cycloaddition of benzonitrile oxide to vinyl ethers with a chiral appendage also proceeded with poor stereoselectivity (dr of 65 35) (196). 

Azasiletanes can be prepared via cycloaddition of iminosilane to vinyl ethers (Equations 22 and 23) <1996JOM43, 1996JOM191>. 

A number of 2-iminothietanes have been prepared from ketenimines and thio-benzophenone ° or thioxanthone. Addition of carbon oxysulfide or carbon disulfide to the phosphonium ylide of a ketenimine 312 gives an imino- 3-dithiolactone as previously noted.Arylsulfonylisothiocyanates undergo cycloaddition at 50°C to vinyl ethers to give 2-iminosulfonylthietanes in 50-76% yields.A ( 2g -I- 2 ) process involving zwitterions was suggested on the basis of the observed stereochemistry. 

The principal method of synthesis of the 1-oxides is the cycloaddition of A-sulfinylsulfonamides, for example, 417, to vinyl ethers." " " " N-phenyl-dimethylketimine" " (correction of an earlier " "" proposed structure), and A-sulfinylamines, for example, 418," ° to ketenes" " " " or alkenes." The adducts obtained from ketene itself are unstable above — 78°750,754,755a Pfeatment... 

Reaction of the 2-ethoaynaphthopyran (70) derived from the cycloaddition of vinyl ether to the benzylidene tetralone (69) with hydroxylamine affords 5,6-dihydrobenzo[h]quinolines (M. C. Bellassoued-Fargeau and P. Maitte, J. heterocyclic Chem., 1984, 21, 1549). 

The Denmark laboratory has developed an elegant tandem [4 + 2]/[3 + 2]-cyclo-addition strategy for the synthesis of a variety of alkaloid natural products (96CR137). Nitroethylene (166) readily undergoes a Lewis acid promoted cycloaddition with vinyl ethers that contain a chiral auxiliary group to give nitronates 168... 

Cycloaddition of 2-pyrones 5 to vinyl ethers 6 serves a key reaction in the synthesis of the important chiron 9, being an A-ring precursor to la-hydroxyvitamin D3. The best diastereose-lectivities were obtained when the appropriate chiral auxiliary was used in the diene component22 or a stereochemically matched pair of chiral diene and chiral catalyst was applied22. 

The methodology based on [2 + 2]cycloaddition of CSI to vinyl ethers was compared with the alternative one based on condensation of the corresponding alcohols with 4-acetoxy-azetidin-2-one (144). In all cases the cycloaddition offered much better stereoselectivity than that found in the condensation [105]. 

Our approach is based on a reaction independently reported by two research groups (75-20). It has been found that azodicarboxylates add to vinyl ethers to provide [4+2] and/or [2+2] cycloadducts. They have shown that the [4+2] cycloaddition reaction is accelerated upon heating or irradiation at 350 nm, presumably due to a partial isomerization of the trans azo compound to the cis isomer, which would be more reactive. In principle, this reaction should be equally efficient with glycals, thereby allowing the introduction of an amino... 

The stereochemical evidence, [36, 38, 39] the much weaker solvent dependence for ketene cycloaddition than for reactions that are known to proceed via polar transition states, [35] and the predominance of steric over electronic substituent effects in the cycloaddition of ketenes to vinyl ethers [37, 42, 43] convinced Huisgen that the reaction occurs mainly, if perhaps not uniquely, as a concerted [ 2, -h,r2a]-cycloaddition. 

At about the same time, Koerner von Gustorf and his associates [51, 52] carried out a parallel investigation of the formation of diazetidines by [2 + 2]-cycloaddition of diazodicarboxylates to vinyl ethers. 

In 2011, Popik and co-workers reported photochemical dehydration of 3-hydroxy-2-naphthalenemethanol (o-naphthoquinone precursor, NQMP, 79) derivatives to o-naphthoquinone methides (oNQMs, 80) [78, 79]. The in situ generated reactive intermediate oNQM underwent facile cycloaddition with vinyl ethers (81) to form photostable benzochromans (82) (Scheme 12). NQMP (79) has two major absorption bands at 275 nm (log s = 4.06) and 324 nm (log s — 3.70) thus it can be photoactivated with either low pressure mercury lamp (254 nm) or fluorescent tubes (300 and 350 nm). The quantum yield of the photoactivation was very high (< 300 = 0.17 0.02 for 79). The in situ generated oNQMs was quenched mostly by... 

As shown in Scheme 11.35, the first [4+2] inverse-demand cycloaddition of electron-deficient heterodienes 166 to vinyl ether 158 was completely enDiels-Alder adduct and acrylate 156 showed a complete facial selectivity. 

Bodipati et al. [96] showed that the highly reactive o-quinone monoamine intermediates 139, generated by treatment of o-aminophenols 136 with PIDA, readily undergo completely regioselective [4 + 2] cycloadditions with vinyl ethers and phenyl vinyl sulfide to afford iV-unsubstituted-l,4-benzoxazine derivatives 138 (Scheme 34). 

Pyrans.— High-pressure [4 + 2] cycloaddition of i -(-)-menthyl glyoxylate and 2,3-dimethylbuta-l,3-diene has been studied, and although it was found that optical yields varied with pressure, the adduct had the (2f )-configuration regardless of pressure (Scheme 36). The [4 + 2] cycloaddition of unsaturated carbonyl compounds to vinyl ethers gives substituted dihydropyrans, a reaction also favoured by increased pressure (Scheme 37). ... 

In place of Ti(O Pr)2-BINOLate, (147) Al-BINOLates (148) are easily prepared by changing the metal source (Scheme 19.29). The polymer-supported chiral Al Lewis acid (148) was used for the enantioselective 1,3-dipolar cycloaddition of diphenyl nitron to vinyl ethers [65]. High levels of exoselectivity (>95 5) and enantioselectivity (96% ee) were obtained. 

The [2-1-2] cycloaddition reaction of methylsulfonylsulfene to vinyl ethers is also known. For example, methylsulfonylsulfene adds to dihydropyran to give a single diastereoisomer 1629. 

Nitronate Facial Selectivity in Intermolecular [3+2] Cycloadditions of Nitronates The majority of asymmetric dipolar cycloadditions of nitronates have been investigated in the context of the tandem [4 + 2]/[3 + 2] cycloadditions of nitroalkenes. With chiral, cyclic nitronates, the facial selectivity is primarily controlled by the steric environment that defines the diastereotopic faces of the nitronate. Nitronates obtained from [4 + 2] cycloadditions with vinyl ethers contain an acetal stereocenter that controls the approach of the dipolarophile. Nitronate 103 (Scheme 16.26) reacts with dimethyl maleate to produce predominantly nitroso acetal distal- QA through a distal approach of the dipolarophile [23]. The proximal approach provided the minor isomer with dr 7/l. Calculations suggest that the distal approach of the dipolarophile that leads directly to a chair-Uke conformation of the six-membered ring is slightly favored over the proximal approach [121]. 

The 2,7-naphthyridine system 53 (Scheme 8.4.18) was combined with 2,4-dinitrochlorobenzene and 2-amino glycerol for in situ reaction of the resulting Zincke salt. The resulting naphthyridinium 54 was trapped by Bradsher cycloaddition with (Z)-vinyl ether 55, providing tetracycle 56 (X-ray) upon internal addition of one of the diastereotopic hydroxymethyl groups to the resulting iminium. This approach was also extended to the use of chiral 2,7-naphthyridinium salts, prepared via the analogous Zincke process. ... 

Stereocontrolled synthesis of oxabicyclic (3-lactam antibiotics via [2- -2] cycloaddition of isocyanates to sugar vinyl ethers 96CC2689. 

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