Intramolecular olefinic aldehyde Prins reactions for the construction of five-membered rings

Abstract

At 100 °C (Reflux Temperature). A solution of 104 mg (0.414 mmol) of 34 dissolved in 7 mL of 95% formic acid was heated at reflux under nitrogen for 12 h. The formic acid was removed with a rotary evaporator, and the residue was diluted with 50 mL of 10% aqueous NaHCOs. The aqueous solution was extracted with 100 mL of CH2C12, and the organic phase was washed with brine, dried over Na2S04, and concentrated to give 112 mg of a yellow oil. The crude product was purified by flash chromatography on 5 g of silica using a solvent gradient ranging from 1:4 to 1:1 EtOAc-hexane. The less polar fractions gave 23.3 mg (24%) of 38. The more polar fractions yielded 63.2 mg (55%) of (lfiS,4SR,7fiS,8fiS,10Sk)-2-aza-8-(formyloxy)-7-methyl-10- (1) Reported in part in the thesis of Bacon, E.

2.03 Prins Reactions and Carbonyl, Imine, and Thiocarbonyl Ene Reactions

“…140 However, aldehyde 224 affords ene adduct 225 in 68% yield with 1 equivalent of Me 2 AlCl at À 72 1C, but not with SnCl 4 . 140 Sarkar reported that the ene reactions of 220 and 222 catalyzed by 5 mol% Sm(III) generated in situ from SmI 2 in CH 2 Cl 2 gives the trans cyclopentanols 226 and 227, respectively rather than the cis cyclopentanols 223 and 225 obtained with Me 2 AlCl or SnCl 4 . 141 This Sm(III) catalyst converts citronellal into a mixture of isopulegol (162a) in 15% yield and neoisopulegol (162b) in 45% yield indicating that it behaves as large catalyst that favors the boat transition state leading to 162b as discussed above (see Scheme 22).…”

“…1 Me 2 AlCl at À 72 1C. 140 However, aldehyde 224 affords ene adduct 225 in 68% yield with 1 equivalent of Me 2 AlCl at À 72 1C, but not with SnCl 4 . 140 Sarkar reported that the ene reactions of 220 and 222 catalyzed by 5 mol% Sm(III) generated in situ from SmI 2 in CH 2 Cl 2 gives the trans cyclopentanols 226 and 227, respectively rather than the cis cyclopentanols 223 and 225 obtained with Me 2 AlCl or SnCl 4 .…”

“…In contrast, intramolecular Prins reactions involve the Lewis or Brønsted acid-catalyzed cyclization of an unsaturated ketone or aldehyde to give a carbocation that can react with water or a halide nucleophile, undergo Wagner -Meerwein type shifts, or lose a proton to give a mixture of allylic and homoallylic alcohols. 140,[183][184][185][186][187][188][189][190][191][192][193] In some cases complex mixtures are obtained, whereas in other cases a single, synthetically useful product predominates. Treatment of 341 with Me 2 AlCl affords cyclopentanol 342 (66%) as a mixture of stereoisomers (see Scheme 41).…”

The Prins Reaction: Advances and Applications

“…Although tin(IV) chloride and dimethylaluminum chloride were considered superior for the cyclization process, titanium(IV) chloride gave mainly chlorhydrins (157) (Scheme 33) [52]. Me 2 AlCl, Et 2 AlCl, EtAlCl 2 , SnCl 4 , TiCl 4 ) were studied in the cyclization of olefinic aldehydes (such as 155) by an internal Prins and/or ene mechanism to afford five-membered rings giving a mixture of products 156-158.…”

Progress in the Synthesis of Guanacastepenes

“…Several attempts to achieve this transformation by ene reaction [35] or thiazolium-catalysed Stetter reaction [36] in order to maintain the unsaturation on the six-membered ring were unsuccessful. Securing the synthesis of bis-enone 102, it was now possible to attempt the final key step of cyclisation to form the seven-membered ring.…”