Facial selectivity 1.3- dipolar cycloadditions, asymmetric

Koizumi and co-workers (38) reported the first asymmetric synthesis of (15)-(—)-a-tropanol (149) via a 1,3-dipolar cycloaddition protocol. Treatment of the chiral dipolarophile 150 with 151 in tetrahydrofuron (THF) delivered cycloadducts exo-152 and endo-153. Although the reaction proceeded with low facial selectivity,... 

Diastereoselective 1,3-Dipolar Cycloadditions. Several examples of high diastereofacial selectivity with homochiral dipolarophiles have been reported. Cycloaddition of (1) with the cyclic dipolarophile (3) occurs with complete r-facial selectivity as a result of addition from the side opposite the bulky sUyloxymethyl group (eq 4). The key step in an asymmetric synthesis of (S)-(—)-cucurbitine involves cycloaddition of (1) with the a,p dehydrolactone (4) to give the pyrrolidine (5) as a single diastere-omer (eq 5). ... 

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]. 

Curran identified Oppolzer s camphor sultam (cf. 81) [77] as a superb chiral auxiliary for the asymmetric [l,3]-dipolar cycloadditions of nitrile oxides (Scheme 18.17) [78-80]. The resulting cycloadducts were generally obtained with high diastereofacial selectivity (dr 90 10). It was proposed that the observed facial differentiation was the result of attack by the nitrile oxide from the top face of conformer 84. This was suggested to be favored on the basis of electronic and steric effects, a proposition that finds support in an X-ray structural analysis of 81 [78, 80]. Cycloaddition of 81 with the nitrile oxide generated in situ from 80 led to isoxazoline 82 in 89 % yield (dr= 92 8). This product constituted a key intermediate in Curran s total synthesis of 83, a bicyclic ketal isolated from ambrosia beetles [80]. 

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