The Synthesis of (+)-Preussin and Related Pyrrolidinols by Diastereoselective Paternò-Büchi Reactions of Chiral 2-Substituted 2,3-Dihydropyrroles

Abstract

The N-alkoxycarbonyl substituted 2,3-dihydropyrroles 3 and 8 are converted to 2-benzyl-3-pyrrolidinols by the Paternò - Büchi reaction followed by hydrogenolysis. Since the addition of the photoexcited benzaldehyde at the unsaturated heterocycle proceeds in a syn fashion, the benzyl group at C-2 and the hydroxy group at C-3 of the product are cis oriented. The simple and facial diastereoselectivities of the Paternò-Büchi 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-dihydropyrroles is presumably due to the nonplanarity of these heterocycles, which forces attack of the carbonyl group on the face with the existing substituent. All-cis-pyrrolidinols are consequently formed after hydrogenolysis. Following this route, a total synthesis of the pyrrolidinol alkaloid (+)-preussin (1) was conducted, which yielded the target compound in a total yield of 11% over nine steps starting from L-pyroglutaminol (11).

Photochemical Approaches to Complex Chemotypes: Applications in Natural Product Synthesis

“…Although the Paternò–Büchi reaction has been less frequently employed in natural product synthesis than the cyclobutane [2 + 2] photocycloaddition reaction, it has for example been utilized in the synthesis of (+)-preussin ( 167 , Scheme 33 ), 166 (±)-oxetanocin ( 171 , Scheme 34 ), 167 and (±)-1,13-herbertendiol ( 176 , Scheme 35 ). 168…”

Four‐Membered Heterocycles: Structure and Reactivity

“…The same reaction with enantiomerically pure aldehyde produced the oxetane with 95% of enantiomeric excess [146]. Bach et al have studied the Paterno-B€ uchi reaction with 2,3-dihydropyrrole and a-alkylated enecarbamate as well [147,148].…”

Photocycloaddition in Natural Product Synthesis

“…Bach and co‐workers' total synthesis of the pyrrolidinol alkaloid (+)‐preussin was achieved in nine steps from L ‐pyroglutaminol in an 11 % yield 101. The key steps of the route included a Paternò–Büchi reaction of benzaldehyde to the dihydropyrrole 126 followed by hydrogenolysis for the efficient carbohydroxylation of the olefin.…”