Ethers, allyl cycloaddition reactions

Schemes 16-19 present the details of the enantioselective synthesis of key intermediate 9. The retrosynthetic analysis outlined in Scheme 5 identified aldoxime 32 as a potential synthetic intermediate the construction of this compound would mark the achievement of the first synthetic objective, for it would permit an evaluation of the crucial 1,3-dipolar cycloaddition reaction. As it turns out, an enantioselective synthesis of aldoxime 32 can be achieved in a straightforward manner by a route employing commercially available tetronic acid (36) and the MEM ether of allyl alcohol (74) as starting materials (see Scheme 16).

Nitrile oxides react with the methyl enol ethers of (Rs)-l -fluoro-alkyl-2-(p-tolylsulfinyl)ethanones to produce (45,5/f,/fs)-4,5-dihydroisoxazoles with high regio-and diastereo-selectivity.87 In the 1,3-dipolar cycloaddition of benzonitrile oxide with adamantane-2-thiones and 2-methyleneadamantanes, the favoured approach is syn, as predicted by the Cieplak s transition-state hyperconjugation model.88 The 1,3-dipolar cycloaddition reaction of acetonitrile oxide with bicyclo[2.2.l]hepta-2,5-diene yields two 1 1 adducts and four of six possible 2 1 adducts.89 Moderate catalytic efficiency, ligand acceleration effect, and concentration effect have been observed in the magnesium ion-mediated 1,3-dipolar cycloadditions of stable mesitonitrile oxide to allylic alcohols.90 The cycloaddition reactions of acryloyl derivatives of the Rebek imide benzoxazole with nitrile oxides are very stereoselective but show reaction rates and regioselectivities comparable to simple achiral models.91. 

Intramolecular cycloaddition of fV-benzyl-substituted 3-O-allylhexose nitrones furnishes chiral oxepane derivatives. The regioselectivity of the cycloaddition depends on several factors such as (1) the structural nature of the nitrone, (2) substitution and stereochemistry at 3-C of the carbohydrate backbone, and (3) substitution at the terminus of the O-allyl moiety. A mixture of an oxepane and a pyran is formed in the intramolecular oxime olefin cycloaddition of a 3-O-allyl carbohydrate-derived oxime <2003T4623>. The highly stereoselective synthesis of oxepanes proceeds by intramolecular nitrone cycloaddition reactions on sugar-derived methallyl ethers <2003TA3899>. 

Silver(I) compounds are known to promote different kinds of cycloaddition. Reactions of 2-alkoxyallyl halides with 1,3-dienes in the presence of silver(I) compounds provide a beneficial route to cycloheptanones [2,3]. When a mixture of 2-(trimethyl-siloxy)allyl chloride 1 and cyclopentadiene (2) is treated with 2 equiv. AgC104 in THF-ether (1 2) at 0 °C, bicyclo[3.2.1]oct-6-en-3-one 3 is produced in 91 % yield [3] (Sch. 1). The 2-(trimethylsiloxy)allyl cation 4 is believed to be involved as a reactive species in the reaction. 

The inside alkoxy effect is useful for predicting the stereoselectivity of nitrile oxide cycloaddition reactions with chiral lylic ethers. The hypothesis states that allylic ethers adopt the inside position and alkyl substituents prefer the sterically less-crowded anti conformation in transition states for these electrophilic cycloadditions . The terms inside and outside are defined in (17) for a hypothetical nitrile oxide cycloaddition transition state. Both ab initio (Gaussian 80 with 3-2IG basis set) and molecular mechanics calculations agree, each predicting the lowest-energy transition state to be the one described, i.e. (18 H outside) just above it lies one where the alkyl group is anti, OR outside and H inside (19 ). As illustrated, the former leads to a product wherein OR and the nitrile oxide oxygen are anti, the latter to one with them syn (Scheme 19). 

The model correcdy predicts (rationalizes) the observed preference for formation of the anti rather than the syn product in the cycloaddition reactions of a wide variety of chiral allylic ethers, thus successfully laying to rest years of frustrated discussion. It also correctly predicts that as the size of R increases (Me - Ph < Et < Pr < Bu ), the preference for transition state structure (18 ) should increase leading to enhanced anti stereoselectivity (Table 15). At first, this prediction seems strange. However, once it is realized that, like the Felkin-Anh model for nucleophilic addition to a carbonyl, the outside position is actually more sterically demanding than the inside, then the prediction is sensible on purely steric grounds. Thus, the angle of approach of the nitrile oxide oxygen to the alkene actually places it nearer the outside than the inside substituent located at the allylic carbon. ... 

The catalytic [2 + 2 + 1]-cycloaddition reaction of two carbon—carbon multiple bonds with carbon monoxide has become a general synthetic method for five-membered cyclic carbonyl compounds. In particular, the Pauson-Khand reaction has been widely investigated and established as a powerful tool to synthesize cyclopentenone derivatives.110 Various kinds of transition metals, such as cobalt, titanium, ruthenium, rhodium, and iridium, are used as a catalyst for the Pauson-Khand reaction. The intramolecular Pauson-Khand reaction of the allyl propargyl ether and amine 91 produces the bicyclic ketones 93, which bear a heterocyclic ring as shown in Scheme 31. The reaction proceeds through formation of the bicyclic metallacyclopentene intermediate 92, which subsequently undergoes insertion of CO to give 93. 

Stereoselection in 1,3-dipolar cycloaddition reactions of chiral allyl ethers 01EJ01039. 

Early extensive accounts of the 4v participation of a,/)-unsaturated carbonyl compounds in [4 + 2] cycloadditions detailed their reactions with electron-deficient dienophiles including a,/3-unsaturated nitriles, aldehydes, and ketones simple unactivated olefins including allylic alcohols and electron-rich dienophiles including enol ethers, enamines, vinyl carbamates, and vinyl ureas.23-25 31-33 Subsequent efforts have recognized the preferential participation of simple a,/3-unsaturated carbonyl compounds (a,/3-unsaturated aldehydes > ketones > esters) in inverse electron demand [4 + 2] cycloadditions and have further explored their [4 + 2]-cycloaddition reactions with enol ethers,34-48 acetylenic ethers,48 49 ke-tene acetals,36-50 enamines,4151-60-66 ynamines,61-63 ketene aminals,66 and selected simple olefins64-65 (Scheme 7-1). Additional examples may be found in Table 7-1. 

During the last decade, use of oxazaborolidines and dioxaborolidines in enantioselective catalysis has gained importance. [1, 2] One of the earliest examples of oxazaborolidines as an enantioselective catalyst in the reduction of ketones/ketoxime ethers to secondary alco-hols/amines was reported by Itsuno et al. [3] in which (5 )-valinol was used as a chiral ligand. Since then, a number of other oxazaborolidines and dioxaborolidines have been investigated as enantioselective catalysts in a number of organic transformations viz a) reduction of ketones to alcohols, b) addition of dialkyl zinc to aldehydes, c) asymmetric allylation of aldehydes, d) Diels-Alder cycloaddition reactions, e) Mukaiyama Michael type of aldol condensations, f) cyclopropana-tion reaction of olefins. 

The preceding study has demonstrated [2.2.1]bicycloheptenyl functionalized resins can be useful and interesting ene components in photoinitiated thiolene polymerizations. The addition of thiols to the unsaturation of this bicyclic system appears to be rapid and exothermic. The relative rates of this addition compared with allylic derivatives and vinyl ethers are quite favorable. The organic resins can be readily prepared from either polyols, f>olyamines, or acrylic precursors (Figure 10) and the yields are generally quite good. When acrylate esters are used as precursors, the cycloaddition reaction occurs spontaneously and no catalysis of the reaction is necessary. 

Slereoselection in 1,3-DC reactions of chiral allyl ethers <01EJ01033> and kinetic resolution by means of cycloaddition reaction, including 1,3-DC of nitrones <01EJO2999>, have been reviewed. 

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