Ketene silyl acetals cycloadditions

The 2+2 cycloadditions of benzyne to cis- and trani-propenyl ether gave cis- and fran -benzocyclobntanes as the main products, respectively [ 117,118], Stereospecific [2+2] cycloaddition reactions were observed between the benzyne species generated by the halogen-Uthium exchange reaction of ort/io-haloaryl triflates and the ketene silyl acetals (Scheme 23) [119],... 

As demonstrated in a series of kinetic experiments by Wittkopp and Schreiner, nitrone N-benzylideneanihne N-oxide can be activated for 1,3-dipolar cycloadditions through double hydrogen-bonding 9 [Ij. Takemoto and co-workers, in 2003, published the nucleophilic addition of TMSCN and ketene silyl acetals to nitrones and aldehydes proceeding in the presence of thiourea organocatalyst 9 (Figure 6.4) [147]. 

In all examples discussed up to now the radical cation of Qo is involved in the reaction mechanism. However, due to the electronic features reduction of the fullerenes leading to radical anions should be much easier performed. For example, a useful method to synthesize 1-substituted l,2-dihydro-[60]fullerenes is the irradiation of Q0 with ketene silyl acetals (KAs) first reported by Nakamura et al. [216], Interestingly, when unstrained KAs are used, this reaction did not yield the expected [2 + 2]-cycloaddition product either by the thermal, as observed by the use of highly strained ketene silyl acetals [217], or by the photochemical pathway. In a typical reaction Q0 was irradiated for 10 h at 5°C with a high pressure mercury lamp (Pyrex filter) in a degassed toluene solution with an excess amount of the KA in the presence of water (Scheme 11). Some examples of the addition of KAs are summarized in Table 11. 

No reaction occurs with vinyl ethers, silyl enol ethers, or ketene silyl acetals, usually used in thermal [2 + 2]cycloaddition reactions, but the present case is the first example of the preparation of a chiral cyclobutanone by a cycloaddition route. 

Reaction of acrylonitrile with ketene acetals.3 Depending on the zinc salt and the solvent, ketene silyl acetals undergo [2+2]cycloaddition or a Michael-type addition with acrylonitrile. The former reaction occurs in CCU with ZnBr2, the latter in CH2C12 with Znl2, with no interconversion. 2-Chloroacrylonitrile can also be used in this way, but substituted acrylonitriles are inactive. 

As mentioned in Section 7.2, when the electron transfer reaction between electron-rich alkenes and excited carbonyl compounds is energetically favorable, the RI pair becomes an important intermediate in photochemical [2 + 2] cycloaddition reactions (Scheme 7.5). The regioselectivity of these reactions may differ from that observed for the PB reaction involving 1,4-triplet biradical intermediates. Typical examples of PB reactions with very electron-rich alkenes, ketene silyl acetals (Eox = 0.9 V vs SCE), have been reported (Scheme 7.11) [27]. Thus, 2-alkoxyoxetanes were selectively formed as a result of the PB reaction with benzaldehyde or benzophenone derivatives, whereas a selective formation of 3-alkoxyoxetanes was observed in less electron-rich alkenes (see Scheme 7.9). When p-methoxybenzalde-hyde was used in the photochemical reaction, the regioselectivity was less than that observed in the case of benzaldehyde. This dramatic decrease in regioselectivity provided evidence that the selective formation of 2-alkoxyoxetanes occurred via RI pair intermediates. It should be noted that the stereoselectivity is also completely different from that associated with triplet 1,4-biradicals (vide infra). 

Regioselective reactions of substituted benzynes are of theoretical and synthetic interest. The [2 + 2] cycloaddition of the benzyne 91 possessing a fused four-membered ring to the ketene silyl acetal 92 yields the cycloadducts 94 and 95 with a high regioselectivity (22 1) (see Scheme 15).104... 

Unsaturated acyl oxazolidinones 1 undergo enantiospecific [2 + 2] cycloadditions with 1,1-di-methylthioethylene and a catalyst consisting of a 1 1 mixture of diisopropoxytitanium dichloride and the chiral diol 243,44. The cyclobutane 3 is obtained in excellent yield with high enantiomeric excess. This is the first example of the enantiospecific [2 + 2] cycloaddition yielding a cyclobutane using an external chiral auxiliary as a chiral catalyst. Unfortunately, the scope of this reaction is quite limited since it fails with vinyl ethers, silyl enol ethers and ketene silyl acetals. 

The same group found that a four-membered ring fused to a benzyne also had a powerful regioselective directing effect in the [2+2] cycloadditions of benzyne, presumably through the severe ring strain [97]. In the reaction of ketene silyl acetal... 

The Suzuki group subsequently reported a dual benzyne cycloaddition protocol starting from bis(sulfonyloxy)diiodobenzene 183 [100], which can be viewed as a synthetic equivalent of 3-methoxy-l,4-benzdiyne (184). When 183 was treated with 1.05 equiv. of n-BuLi in the presence of ketene silyl acetal 175 at -95 °C, a benzyne intermediate was generated on the iodo-triflate side of the arene, affording the mono-cycloadduct 185 in 11% yield (Scheme 12.51). 

SCHEME 12.20 [2+2] Cycloadditions with ketene silyl acetals. 

Theoretical calculations at DFT level agree that the reactions of nitrones with silyl ketene acetal proceeds via 1,3-dipolar cycloaddition followed by the transfer of the silyl group, yielding an open-chain product (641). 

Triazines are generally more reactive in [2 + 4] cycloaddition in comparison with 1,2,3-tria-zines. The wide variety of dienophiles can be employed enamines, enaminones, vinyl silyl ethers, vinyl thioethers, cyclic ketene jV,O-acetals, /V-phenylmaleimide, 6-dimethylaminopentafulvene, 2-alkylidene-imidazolidines (cychc ketene aminals), cyclic vinyl ethers, arynes, benzocyclopropene, acetylenes, and alkenes like ethylene, (Z)-but-2-ene, cyclopentene, cyclooctene and bicyclo[2.2.1]hept-2-ene, hexa-1,5-diene, cycloocta-1,5-diene, diallyl ether, cyclododeca-l,5,9-triene,... 

A comparative study between the Patemb-Biichi reaction of aromatic aldehydes with silyl 0,0-ketene acetals, 109, and 0,A-ketene acetals, 111, has highlighted sulfur atom effects on both regio- and stereoselectivities (Scheme 21) <1996TL5901, 1998J(P1)3253, 1998J(P 1)3261, 2000JA4005>. Cycloadditions with 109 were not stereoselective and gave 2-siloxyoxetanes 110. By contrast, reactions with 111 favored the formation of tram-3-siloxyoxetanes, 112. 

Paternd-Biichi reactions [152] this competition has been investigated for electron-rich alkene substrates for several combinations of carbonyl compounds and electron-donors, e.g. a-diketones and ketene acetals [153], aromatic aldehydes and silyl ketene acetals, and enol ethers. In polar solvents, the assumption of a 1,4-zwitterion as decisive intermediate is reasonable. This situation then resembles the sequence observed for ET-induced thermal [2 -I- 2]-cycloaddition reactions [154]. Both regio- and diastereoselectivity are influenced by this mechanistic scenario. The regioselectivity is now a consequence of maximum charge stabilization and no longer a consequence of the primary interaction between excited carbonyl compound and alkene. Whereas 3-alkoxyoxetanes are preferentially formed from triplet excited aldehydes and enolethers, 2-alkoxyoxetanes result from the reaction of triplet excited ketones or aldehydes and highly electron-rich ketene silylacetals (Scheme 40) [155]. 

Drawing from their success with catalytic [4 + 2] cycloaddition, Lectka group developed another highly enantioselective cycloaddition of o-quinone methide (o-QM) with silyl ketene acetals, using a chiral cinchona alkaloid derived ammonium, N-(3-nitrobenzyl)quinidinium fluoride Is, as a precatalyst. The free hydroxyl group of the cinchona alkaloid moiety was crucial to high optical induction. A variety of silyl ketene acetals had been screened to afford the cycloadducts 22 with good ee (72-90%) and excellent yield (84—91%) (Scheme 10.26) [35]. 

Scheme 10.26 Cycloaddition of o-quinone methide with silyl ketene acetal.

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