Academic literature on the topic 'Prins cyclization'

The tetracyclic alkaloids Nankakurine A and Nankakurine B were isolated from the club moss Lycopodium hamiltonii. A preliminary study of the biological activity of Nankakurine A suggested that it could induce secretion of neurotrophic factors and promote neuronal differentiation. The key step in the first syntheses of Nankakurine A and of Nankakurine B, reported (J. Am. Chem. Soc. 2008, 130, 11297) by Larry E. Overman of the University of California, Irvine was the intriguing intramolecular aza-Prins cyclization of 1 to 2. The starting material for the synthesis was 5-methyl cyclohexenone 6, prepared from (R)-pulegone. The diene 5 was prepared from the alkyne 4, following the procedure developed by Diver. There were two issues in developing the Diels-Alder addition of the enone 4 to the diene 6. The first was the relative lack of reactivity of 4 as a dienophile. The other issue was the ready epimerization of the product ketone 9. Both of these problems were solved using the activation method devised by Gassman. Condensation of 4 with 7 in the presence of the bis-silyl ether 7 and the diene 6 at cryogenic temperatures led to the ketal 8. It is thought that the active dienophile was the cation 11. Gentle hydrolysis of the ketal 8 was effected with minimal epimerization. Reductive amination with the hydrazide 10 proceeded with high diastereocontrol, to give the precursor 1. The intramolecular aza-Prins cyclization of 1 to 2 proceeded well, though the desired tetracyclic 2 was only observed when base was included in the reaction medium. In the absence of base, tricyclic alkenes dominated. Reduction of the N-N bond of 2 proceeded smoothly with freshly prepared SmI2 . After reductive methylation, hydrogenation removed the benzyl ether, and AlH3 converted the benzamide to the benzyl amine. At low temperature, mesylation of the alcohol was apparently faster than mesylation of the secondary amine, enabling cyclization to 14. Removal of the benzyl protecting group gave Nankakurine A, which was successfully methylated to give Nankakurine B.

Since five-membered ring ethers often do not show good selectivity on equilibration, single diastereomers are best formed under kinetic control. Aaron Aponick of the University of Florida demonstrated (Organic Lett. 2008, 10, 669) that under gold catalysis, the allylic alcohol 1 cyclized to 2 with remarkable diastereocontrol. Six-membered rings also formed with high cis stereocontrol. Ian Cumpstey of Stockholm University showed (Chem. Commun. 2008, 1246) that with protic acid, allylic acetates such as 3 cyclized with clean inversion at the allylic center, and concomitant debenzylation. J. Stephen Clark of the University of Glasgow found (J. Org. Chem. 2008, 73, 1040) that Rh catalyzed cyclization of 5 proceeded with high selectivity for insertion into Ha, leading to the alcohol 6. Saumen Hajra of the Indian Institute of Technology, Kharagpur took advantage (J. Org. Chem. 2008, 73, 3935) of the reactivity of the aldehyde of 7, effecting selective addition of 7 to 8, to deliver, after reduction, the lactone 9. Tomislav Rovis of Colorado State University observed (J. Org. Chem. 2008, 73, 612) that 10 could be cyclized selectively to either 11 or 12. Nadège Lubin-Germain, Jacques Uziel and Jacques Augé of the University of Cergy- Pontoise devised (Organic Lett. 2008, 10, 725) conditions for the indium-mediated coupling of glycosyl fluorides such as 13 with iodoalkynes such as 14 to give the axial C-glycoside 15. Katsukiyo Miura and Akira Hosomi of the University of Tsukuba employed (Chemistry Lett. 2008, 37, 270) Pt catalysis to effect in situ equilibration of the alkene 16 to the more stable regioisomer. Subsequent condensation with the aldehyde 17 led via Prins cyclization to the ether 18. Paul E. Floreancig of the University of Pittsburgh showed (Angew. Chem. Int. Ed. 2008, 47, 4184) that Prins cyclization could be also be initiated by oxidation of the benzyl ether 19 to the corresponding carbocation. Chan-Mo Yu of Sungkyunkwan University developed (Organic Lett. 2008, 10, 265) a stereocontrolled route to seven-membered ring ethers, by Pd-mediated stannylation of allenes such as 21, followed by condensation with an aldehyde.

The Prins cyclization is a powerful approach for the construction of oxygen-containing heterocycles. B.V. Subba Reddy at the Indian Institute of Technology has reported (Tetrahedron Lett. 2012, 53, 3100) an approach to 2,6-dioxabicyclo[3.2.1]octanes 2 by way of a tandem Prins reaction/intramolecular acetalization of the diol 1 and a variety of aldehydes. Christine L. Willis of the University of Bristol utilized (Angew. Chem. Int. Ed. 2012, 51, 3901) nontraditional γ, δ-unsaturated alcohols 3 for a Prins-type strategy to access bicyclic heterocycles 5, while Zhenlei Song of Sichuan University employed (Angew. Chem. Int. Ed. 2012, 51, 5367) a bis(silyl) homoallylic alcohol 7 in the synthesis of structures such as 8, corresponding to the B ring of the bryostatins. In a mechanistically related process, the conversion of unsaturated ketones 9 to tetrahydropyranyl products 11 by treatment with a boronic acid 10 and triflic anhydride was described (Org. Lett. 2012, 14, 1187) by Aurelio G. Csáky at the Universidad Complutense in Spain. A powerful approach to heterocycles is via the ring expansion of smaller, and especially strained, ring systems. Jon T. Njardarson of the University of Arizona has been exploring such strategies and has reported (Angew. Chem. Int. Ed. 2012, 51, 5675) the conversion of vinyl oxetanes to dihydropyrans via catalysis by transition metals or Brønsted acids. The use of a chiral catalyst such as 13 allowed for the enantioselective conversion of divinyl oxetane 12 to enantioenriched dihydropyran 14. Meanwhile, Amir H. Hoveyda at Boston College and Richard R. Schrock at MIT have developed (J. Am. Chem. Soc. 2012, 134, 2788) a highly reactive and stereoselective catalyst for the ring-opening/cross-metathesis of several ring systems such as 15 with enol ethers. Notably, reactions occur rapidly (e.g., 10 min) using as little as 0.15 mol% catalyst. An alkynyl cyclopropyl ketone such as 17 can be converted (Angew. Chem. Int. Ed. 2012, 51, 4112) to products 18 by treatment with a gold/silver catalyst mixture, as shown by Zhongwen Wang at Nankai University. Notably, the oxabicyclic ring structure contained within 18 is present in a diversity of natural product structures.

Briarellin F 4 is an elegant representative of the complex polycyclic ethers produced by soft corals such as Briareum abestinum. Larry E. Overman of the University of California, Irvine, developed (J. Org. Chem. 2009, 74, 5458) a triply convergent approach to 4, the central feature of which was the Prins-pinacol combination of 1 with 2 to give 3. The aldehyde 2 was assembled by Wittig homologation of the aldehyde 5 with the phosphorane 6, followed by metalation and formylation. The aldehyde 10 was prepared by opening the enantiomerically pure epoxide 8 with the acetylide 9. Hydroboration of carvone 11 could not be effected with sufficient diastereocontrol. As an alternative, the mixture of diols was oxidized to the lactone 12 . Kinetic quench of the derived silyl ketene acetal followed by reduction led to the diastereomerically pure crystalline diol 13. This key intermediate will have many other applications in target-directed synthesis. The ketone 14 was converted to the alkenyl iodide 15 by stannylation of the enol triflate, followed by exposure of the stannane to N-iodosuccinimide. Addition of the alkenyl iodide 15 to the aldehyde 10 gave the diol 1 as an inconsequential 3:1 mixture of diastereomers. This mixture was combined with the aldehyde 2 to give, via Lewis acid–mediated rearrangement of the initially prepared acetal, the aldehyde 3 . The aldehyde 3 was readily decarbonylated by irradiation in dioxane. Face-selective Al-mediated epoxidation of the derived homoallylic alcohol proceeded with 10:1 selectivity, and subsequent MCPBA epoxidation of the cyclohexene was also secured with 10:1 facial control. This set the stage for the triflic anhydride–mediated closure of the six-membered ring ether. The Nozaki-Hiyama-Kishi cyclization of 18 proceeded with remarkable selectivity, delivering briarellin E 19 as a single diastereomer. Dess-Martin oxidation converted 19 into briarellin F 4.