The synthesis of (+)-preussin and related pyrrolidinols by diastereoselective Paterno-Buchi reactions of chiral 2-substituted 2,3-dihydropyrroles

The N-alkoxycarbonyl substituted 2,3-dihydropyrroles 3 and 8 are converted to 2-benzyl-3-pyrrolidinols by the Paterno-Buchi reaction followed by hydro genolysis. Since the addition of the photoexcited benzaldehyde at the unsat urated heterocycle proceeds in a syn fashion, the benzyl group at C-2 and t he hydroxy group at C-3 of the product are cis oriented. The simple and fac ial diastereoselectivities of the Paterno-Buchi reaction were studied more closely and the relative configuration of the products was elucidated. The thermodynamically less stable endo product is formed as a result of simple diastereoselection. The face differentiation in 2-substituted 2,3-dihydropy rroles is presumably due to the nonplanarity of these heterocycles, which f orces attack of the carbonyl group on the face with the existing substituen t. All-cis-pyrrolidinols are consequently formed after hydrogenolysis. Foll owing this route, a total synthesis of the pyrrolidinol alkaloid (+)-preuss in (1) was conducted, which yielded the target compound in a total yield of 11% over nine steps starting from L-pyroglutaminol (11).