Trienes intramolecular asymmetric

Corey later reported that BLA 59a catalyzes the intramolecular Diels-Alder reaction of several triene aldehydes and esters with high asymmetric induction to yield the corresponding 6/5-trons-fused bicyclic structures (Scheme 5.74) [143]. 

Thus, (2R)-pumiliotoxin C (214) has been prepared from (R)-norvaline (212). The asymmetric center in the triene (213) controls the configuration at three carbon atoms 210). a-Kainic acid, isolated from the algae Digena simplex and Centrocerus clavulatum, was prepared by total synthesis. Its enantioselective synthesis involved a stereocon trolled intramolecular cycloaddition of a (S)-glutamic acid211). Asymmetric cycloadditions also play a decisive role in the synthesis of chiral cytochalasins. In this case 212> the primary chiral information was carried by (S)-alanine and (S)-phenylalanine, respectively. 

When TMM equivalents are tethered to alkenes, intramolecular cyclization generates bicyclic methylene-cyclopentane derivatives. Cyclization of 394, for example, led to a 51% yield of 395 along with 18% of the uncyclized triene, 396. 35 jhe cyclization reaction proceeded with excellent diastereoselectivity, as shown. Trost has also examined the attachment of chiral auxiliaries to the alkene partner to give asymmetric induction in reactions with TMM equivalents.231... 

Lewis acid-catalyzed intramolecular Diels-Alder reactions of trienes, bearing an inducing moiety, e.g. oxazolidinones 62 or sultam 63, have been widely examined and employed in natural product synthesis. The cycloadducts were obtained in high yield with excellent stereoselectivities. Among the Lewis acids studied in asymmetric intramolecular Diels-Alder reactions with auxiliary 11, a chiral catalyst [(Bomyl)AlCl2] proved to be highly efficient (72% de, 25-75%). 

Overman and Rosen [76] reported a total synthesis of spirotryprostatin B (137), a structurally novel diketopiperazine alkaloid, that featured a cascade Mizoroki-Heck cyclization/jj -allylpalladium capture process and the exploration of a related catalytic asymmetric sequence (Scheme 16.36). The plan was to relay the relative configurations of the quaternary stereocentre and the adjacent tertiary stereocentre in the natural product from the geometry of the trisubstimted alkene in the Mizoroki-Heck cyclization substrate. It was anticipated that the favoured 5-exo intramolecular Mizoroki-Heck cyclization of enantiopure triene precursor 135 would generate an -allylpalladium intermediate, with a chiral palladium catalyst controlling the absolute configuration of the initially formed quaternary carbon stereocentre. 

Transannular intramolecular Diels-Alder (TADA) cyclizations have been widely employed. Although a great deal has been learned about relative stereocontrol, little progress had been made on asymmetric catalysis of the cyclization of prochiral trienes such as 20. Eric N. Jacobsen of Harvard University has now found Science 2007, 317, 1736) that the o-fluoro complex 21 served effectively. The power of this approach was illustrated by the conversion of the adduct 22 into the natural product 11,12-diacetoxydrimane 23. 

In the study of total synthesis of the CP-molecules by Nicolaou group, the asymmetric intramolecular Diels-Alder reaction of prochiral triene compound 44 was conducted under the influence of chiral aluminum Lewis acid catalyst 45, albeit the low level of enantioselectivity (Scheme 34) [58, 59]. 

The use of amides and imides as chiral auxiliaries in [4 + 2]-cycloadditions has been the subject of numerous investigations. Oppolzer reported the use of camphorsultam 112 in asymmetric Diels-Alder reactions [26, 67. 68], The camphor sultam is readily available in both enantiomeric forms from cam-phorsulfonyl chloride. Acrylate 113 was found to react with cyclopentadiene in the presence of EtAlCl2 to give 115 with high selectivity (endo/exo = 99.5 0.5, dr = 97.5 2.5, Equation 10) [67]. Oppolzer also reported that triene 116 participated in an intramolecular Diels-Alder cycloaddition reaction to afford endo product 117 in 71 % yield and 96.5 3.5 dr (Scheme 17.19) [69]. This bicyclic product was subsequently converted into the pyridine alkaloid (-)-pulo upone (118). 

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