Epoxide-opening cascades

VUotijevic I, Jamison TF (2007) Epoxide-opening cascade promoted by water. Science... 

The beauty of this method is that iterative processes can proceed and that polycyclic frameworks can be constructed. In the formal synthesis of (-)-brevisin, compound 36 was obtained by using a rhodium-catalyzed e do-selective epoxide-opening cascades. Thus, when THP 35 was treated with [Rh(CO)2Cl]2, compound 36 was formed and then transformed to primary alcohol 37 which is a precursor of (-)-brevisin (Scheme 20) (2015JA6941). 

A kinetic study, using complex pathways simulator (COPASI) software, NMR spectroscopy, and product studies, has shown that the endo-selective epoxide-opening cascade or domino reaction by H2O converting the diepoxy alcohol (7) into the tetrahydropyran triad (8) in neutral water proceeds by a stepwise mechanism initiated by a slow, low regioselective endo.exo = 2.0 1) 5 2 reaction that is followed by a fast, highly regioselective endo exo = 19 1) 5 2 reaction. ... 

A group of polycyclic polyether natural products are of special interest owing to their fascinating structure and biological activities. One of the proposed biosynthetic origins of these molecules features an epoxide-opening cascade pathway. Shi asymmetric epoxidation of un-activated alkenes has been frequently employed in the preparation of polyepoxide intermediates. McDonald and co-workers studied a series of tandem e 7o-selective and stereospecific oxacyclization of polyepoxides mediated by Lewis acid. Polyepoxides, such as 64, can be obtained from the epoxidation of triene 63 with ketone 2. Furthermore, a cascade cyclization, initiated by a Lewis acid-promoted epoxide opening of 64, furnished the desired polyether 65. 

Inspired by the postulated biogenesis of polyether compounds, a valuable cascade cyclization approach was developed on the predictable carbocation formation of the Nicholas reaction using very mild acidic conditions (silica gel as promoter) with excellent yields via very often inefficient epoxide opening cascade (13AGE3659). 

Recent progress in the synthesis of oxepanes and medium ring ethers. Tetrahedron, 68, 6999-7018. (d) Vilotijevic, L, Jamison, T. F. (2009). Epoxide-opening cascades in the synthesis of polycyclic polyether natural products. Angewaudte Cheruie lutematioual Edition, 48, 5250-5281. (e) Snyder, N. L., Haines, H. M., Peczuh, M. W. (2006). Recent developments in the synthesis of oxepines. Tetrahedron, 62, 9301-9320. (f) For medium-ring thiacycles Rosowsky, A. 1972. In Weissberger, A., Taylor, E. C. (Eds.) Heterocyclic Compounds. Wiley, New York. Vol. 26. 

Tanuwidjaja, J., Ng, S.-S., Jamison, T. F. (2009). Total Synthesis of ent-dioxepandehydrothyrsiferol via a bromonium-initiated epoxide-opening cascade. Journal of the American Chemical Society, 131,12084-12085. 

Terpene polyethers have also been proposed to arise through epoxide-opening cascade reactions. These structures are distinct from the other compound classes in this chapter because their carbon frameworks are not derived from polyketide synthase pathways. However, epoxide hydrolases are commonly encountered in terpene biosynthetic pathways [18], indicating that epoxides are viable intermediates in the construction of these compounds. 

Xiong used an acid-mediated epoxide-opening cascade to prepare a penta-tetrahydrofuran structure for the synthesis of the tetra-tetrahydrofuran natural product omaezakianol (152 Scheme 4.31) [66]. This allowed for the synthesis of cyclization precursor 153 from squalene. Exposing 153 to CSA provided pentacycle 154 in a 21% yield that includes the formation of the epoxides. Reductive opening resulted in... 

Heffron, T.P., Simpson, G.L., Merino, E., and Jamison, T.F. (2010) Ladder polyether synthesis via epoxide-opening cascades directed by a disappearing trimethylsilyl group. J. Org. Chem., 75, 2681-2701. 

A Lewis acid-mediated epoxide opening cascade has been reported to provide the oxygenated core of pactamycin (Scheme 67). ... 

In recent studies, Jamison and coworkers reported the formation of tetrahydro-pyran via cascade epoxide-opening reactions in water (Scheme 9) [96]. In this study, polytetrahydropyran precursor, such as 53, was synthesized from the epoxidation of polyalkene 52. 

Independently, Prasad and Shimizu (24) as well as Lee et al. (25) proposed that brevetoxin A is biosynthesized from the cyclization of a polyepoxide precursor in a series of Sn2 R,R)-trans epoxide openings (Fig. 4c). Galfimore and Spencer (3) argue that the nine disfavored endo-tet closures required for this mechanism makes it mechanistically unlikely and point out that an alternative cascade of Sn2 epoxide openings in the opposite direction from all (S,S)-trans epoxides yields the same structure. 

While obviously natural enediynes 2-4 behave in the same way, in dynemicin the cascade of events is different. However, this molecule also displays a delivery unit (the anthraquinone), a safety catch (the epoxide) and a trigger (the quinone). Bioreduction of the quinone unleashes two lone pairs (one on the nitrogen and one on the upper hydroquinone oxygen) which bring about intramolecular epoxide opening. ... 

The bis(tetrahydrofuranyl) Annonaceous acetogenin ( + )-(15,16,19,20,23,24)-hexepiuva-ricin (74), has been synthesized utilizing a polyepoxide cascade reaction. The diiodide 70 is transformed into the bis-allylic alcohol 72, which is subsequently converted to a C2-sym-metric diepoxide utilizing the Sharpless asymmetric epoxidation reaction. Selective mono-tosylation of the primary hydroxyl groups served to desymmetrize the system. An acid-catalyzed deketalization followed by simultaneous epoxide opening affords the erythro trans threo trans erythro-conf gmdXion present in the tosylate 73. Transformation of 73 to the desired 74 completes the synthesis [32] (Scheme 17). 

In an investigation related to the total synthesis of (-i-)-3a-hydroxyreynosin, Cuerva and Oltra discovered that the products of a Ti(III)-mediated epoxide-opening/cycUzation cascade varied with the presence or absence of water. In dry THF they obtained the product originally desired, with an exocyclic A [3,14] double bond, but the addition of water resulted in the formation of the reductively cychzed product in Scheme 1.4. Apparently H is transferred from the titanium-water complex to the cyclized radical [35-37]. 

Scheme 1.4 Epoxide opening/reductive cyclization cascade.

The fused tricyclic system of hirsutellones A-C, embodied by 125, was generated by a concise and stereoselective intramolecular epoxide opening/Diels-Alder cascade reaction of epoxide... 

Corey and coworkers reported that (i )-2,3-dihydroxy-2,3-dihydrosqualene (104) was rapidly converted into proposed glabrescol 90 in 31% overall yield by enantio-selective pentaepoxidation with ketone 42 and subsequent cascade epoxide opening (Scheme 3.34) [69]. In their efforts to determine the correct stmcture of glabrescol, tetraene 106 was epoxidized with ketone 42. The resulting epoxide 107 was transformed into a chiral C2-symmetric pentacydic oxasqualenoid 109 (Scheme 3.35), which matches the reported isolated natural product glabrescol [70, 71]. 

The purpose of this chapter is to describe the use of epoxides as biosynthetic precursors for cyclic ethers. The advances that allow for predictable chemical synthesis based on epoxide opening, including the development of models for regiocontrol in intramolecular ring-opening reactions and stereoselective synthesis, will be described. Numerons examples of epoxide cascade reactions in natural product synthesis will conclude the chapter. 

The epoxide-opening reactions in the monensin synthetic pathway lead to the formation of tetrahydrofuran structures through nucleophilic addition to the proximal carbon. An alternative pathway would proceed through nucleophilic addition to the distal carbon, which would provide a tetrahy-dropyran structure. The formation of tetrahydrofurans is preferred over the formation of tetrahydropyrans under mildly acidic conditions, as will be discussed later in this chapter. Therefore questions arose as to whether enzymes are involved with the epoxide cascade reaction. Enzymatic involvement was demonstrated during studies on the biosynthesis of lasalocid A (8). The precursor of 8 should be diepoxide 9 in accord with the Cane-Cehner-Westley hypothesis. However, the formation of the tetrahydropyran in the... 

Morimoto used two epoxide-opening strategies for the total synthesis of enshuol (147 Scheme 4.30) [65]. An efficient acid-mediated exo-cascade was utilized to convert 148 to 149. A six-step sequence was used to prepare epoxide 150 from 149. An enbulky Lewis acid TIPSOTf, in... 

Morimoto employed Hoye s strategy of promoting cascade cyclization reactions through a base-mediated Payne rearrangement in the total synthesis of intricatetraol (181 Scheme 4.40) [75]. Diepoxide 182 reacts with LiOH to initiate a Payne rearrangement that results in an exo-cycliza-tion. The resulting epoxide opens to form the diol in 183 in the same transformation. Fnnctional gronp interconversions and dimerization provided the natnral product. 

SCHEME 21.40. Epoxide-opening/1,2-methyl and hydrogen migration/O-cycUzation cascade for the synthesis of (-l-)-stachyflin. 

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