Oxygen substituents, cycloaddition

The cycloaddition of a nitrile oxide with a chiral allylic ether affords an isoxazoline with selectivity for the pre/-isomer. This selectivity increases with the size of the alkyl substituent and is insensitive to the size of the allyl oxygen substituent. However, allyl alcohols tend to form the / ar/ isomcr preferentially, although the selectivity is often low.427"434 The product of dipolar cycloadditions based on nitrile oxides, the isoxazoline moiety, can be converted into a large variety of functional groups under relatively mild conditions.3 Among other products, the addition can be used to prepare P-hydroxy ketones (Scheme 26.17).435 The isoxazoline moiety can be used to control the relative stereochemistry through chelation control.436,437... 

Pierlot, C., Poprawski, J., Marko, J. and Aubry, J.-M. (2000) Effects of oxygenated substituents on the [4 + 2] cycloaddition of singlet oxygen in the photooxygenation of water-soluble naphthyl ethers. Tetrahedron Letters, 41 (25), 5063-5067. 

Oxyallyl cations bearing oxygen substituents have been synthesized from 15 and catalytic TMSOTf (entry 2) [33], from 16andLiC104/Et3N (entry 3) [34], and from the reaction of pyruvaldehyde directly with SnCl4 (entry 4) [35]. Oxyallyl cations from 17 undergo cycloaddition with furan to give nitrile-substituted oxabicyclic compounds (entry 5) [34b]. 

The hetero -Diels-Alder (HDA) reaction provides the opportunity to incorporate a heteroatom into the Diels-Alder product. Most commonly the catalytic asymmetric version of this reaction involves the reaction between an aldehyde (8.122) and a reactive diene (8.123) (typically with one or two oxygen substituents attached). Normally, the isolated products, after acidic work-up, are the enones (8.124). The products can either be formed by a direct cycloaddition or via a two step aldol-Michael sequence, according to Figure 8.5. 

Cycloaddition of jo-bromobenzenesulfonyl azide to alkynyl ethers affords equilibrium mixtures of triazole and diazocarbox-imidate. In the case of the ether in which both the carbon and the oxygen substituents of the alkynyl ether are methyl, only the triazole is found (eq 8). ... 

Intramolecular cycloadditions of furans are a useful method for creating an oxygenated cyclohexane ring in rigid cycloadducts. Thus, a MeAICI2-catalyzed intramolecular reaction [40] of compounds 34 leads stereoselectively to tricyclic cycloadducts (Equation 3.8). The reaction yield is strongly dependent on the quantity of the catalyst and the type of substituent at the olefmic double bond. Cycloadduct 35 (R = R2 = Me, Ri = R3 = R4 = H) was then converted [40b] into 1,4-epoxycadinane (36). 

When the steric size of the substituents increases, no adducts with bulky (Et3N) or less basic (EtzO) donors are formed with (Me3C)2Si= NSi(CMe3)3.14 The structure of the benzophenone adduct is quite remarkable.16 Instead of the expected cycloaddition product, the carbonyl oxygen atom is coordinated to the undersaturated silicon atom. 

The high stereopreference was rationalized by considering complex 388 in which an attractive n-n donor-acceptor interaction favors co-ordination of the dienophile to the face of the boron center which is cis to the 2-hydroxyphenyl substituent. Hydrogen bonding of the hydroxyl proton of the 2-hydroxyphenyl group to an oxygen of the adjacent B—O bond played an important role in the asymmetric induction. Protection of this hydroxy functionality with a benzyl group caused reversal of enantioselectivity in the cycloaddition of cyclopentadiene with methacrolein (model 389)244. 

While the fadhty and effidency of the [5+2] cycloaddition of oxygen-substituted VCPs could be attributed solely to the electronic contribution of the heteroatom substituent, it could also be a consequence of its conformational influence. Substitution of a VCP, particularly at the 1-position, has been shown to reduce the difference in energy between the s-cis (local minimum) and s-trans (global minimum) conformations through steric effects [50]. Based on the proposed mechanisms for the [5+2] cycloaddition, only the s-cis conformations, 190 and 192, can lead to productive reaction, so biasing intermediates toward this conformation could therefore accelerate the reaction (Scheme 13.16). 

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