Olefin-epoxide cyclizations

Keywords Acetals, Acylals, Allylations, Bismuth(III), 3,4-Dihydro-2//-l -benzopyrans, Ene reactions, Epoxide-olefin cyclizations, Piperidines, Tetrahydro-quinolines, THP ethers... 

Epoxides can also serve as effective carbocyclization promotors, either through a polyene cyclization, as in the biomimetic epoxy-olefin cyclization of 100 in the presence of boron trifluoride etherate <99CC325>, or by a Friedel-Crafts approach, as exemplified by the cycli-alkylation of arylalkyl epoxides 102 under the influence of solid acid catalysts <99EJOC837>. 

Stereospecific 2,3-epoxidation of squalene, followed by a nonconcerted carbocationic cyclization and a series of carbocationic rearrangements, forms lanosterol [79-65-0] (77) in the first steps dedicated solely toward steroid synthesis (109,110). Several biomimetic, cationic cydizations to form steroids or steroidlike nuclei have been observed in the laboratory (111), and the total synthesis of lanosterol has been accomplished by a carbocation—olefin cyclization route (112). Through a complex series of enzyme-catalyzed reactions, lanosterol is converted to cholesterol (2). Cholesterol is the principal starting material for steroid hormone biosynthesis in animals. The cholesterol biosynthetic pathway is composed of at least 30 enzymatic reactions. Lanosterol and squalene appear to be normal constituents, in trace amounts, in tissues that are actively synthesizing cholesterol. 

The chemical simulation of this biosynthetic process has been developed as an important methodology in organic synthesis. Van Tamelen reported the add-catalyzed cyclization of chiral terminal epoxides of polyprenoids [11]. In contrast, Johnson adopted the acid-catalyzed cyclization of poly-prenic acetals derived from chiral diols [12]. In addition to these pioneering studies, the biomimetic polyene cycliza-tions of polyprenoids, which are induced by a variety of electrophiles such as proton, oxonium ion, halonium ion [13], or metal ion [14], have also been developed. Despite extensive studies on these diastereoselective olefin cyclizations, enantioselective processes using synthetic chiral catalysts had not been developed for a long time. In 1999, Yamamoto s... 

Olefins have a rich history in organic chemistry and consequently there is a vast array of transformations available to this fundamental functional group. This chapter discusses the classic methods for stereoselective oxidations of olefins, spanning the range from diastereoselective [16-18] and enantioselec-tive [19-29] formation of epoxides to their asymmetric ring-opening reactions [30-33], stereoselective formation of aziridines [34—37], iodolactoniza-tions and other olefin cyclizations induced by electrophiles [38, 39], dihy-droxylations [40-49], and aminohydroxylations [47, 50] (Figure 9.1). 

Olefin isomerization can be catalyzed by a number of catalysts such as molybdenum hexacarbonyl [13939-06-5] Mo(CO)g. This compound has also been found to catalyze the photopolymerization of vinyl monomers, the cyclization of olefins, the epoxidation of alkenes and peroxo species, the conversion of isocyanates to carbodiimides, etc. Rhodium carbonylhydrotris(triphenylphosphine) [17185-29-4] RhH(CO)(P(CgH )2)3, is a multifunctional catalyst which accelerates the isomerization and hydroformylation of alkenes. 

Squalene epoxidase, a key enzyme in the biosynthesis of cholesterol (9), epoxidizes one face of one of the three different olefins in squalene (7) to give squalene epoxide (8), which then cyclizes eventually to give cholesterol (9) (Scheme 1). The AD of squalene (7)... 

Following Uskokovic s seminal quinine synthesis [40], Jacobsen has very recently reported the first catalytic asymmetric synthesis of quinine and quinidine. The stereospecific construction of the bicyclic framework, introducing the relative and absolute stereochemistry at the Cg- and expositions, was achieved by way of the enantiomerically enriched trans epoxide 87, prepared from olefin 86 by SAD (AD-mix (3) and subsequent one-pot cyclization of the corresponding diol [2b], The key intramolecular SN2 reaction between the Ni- and the Cg-positions was accomplished by removal of the benzyl carbamate with Et2AlCl/thioanisole and subsequent thermal cyclization to give the desired quinudidine skeleton (Scheme 8.22) [41],... 

The tetraene precursor 14, assembled in a similar way to 11, underwent smooth cyclization using the ruthenium initiator 3 (0.1 equiv) to give macrolactone 15, again in good yield and with complete E-selectivity. Despite the incorrect olefin geometry, transformation into epoxides 16 provided further encour-... 

We have chosen epoxy olefin 10 as substrate for our initial examinations for two reasons. Firstly, 10 is synthesized in a straightforward manner from al-lyl diethyl malonate by epoxidation and an Sn2 reaction with prenyl bromide. Secondly, it is known from the work of others [17-20] and ourselves [65, 66,73,74] that compounds similar to 10 cyclize to yield mainly the essential ds-fused radicals with selectivities of about 85 15 to 90 10. 

The formation of THF derivatives through SH2 reaction with mono- and disubstituted olefins was also investigated to define the overall scope of the transformation. Some of our results are summarized in Table 8. Not surprisingly, the monosubstituted alkene 53 gave essentially none of the desired 54 (5%). It is well known that the primary radicals produced during the 5-exo cyclization are rapidly trapped by Cp2TiCl to yield the products of a reductive cyclization [17-20,65,66,73,74]. Epoxides containing disubstituted... 

After epoxidation of the terminal olefin in syn-89 the pyrrolidine 91 was formed by reductive cleavage of the Cbz-protection and concomitant Sn2 cyclization of the free amine to epoxide 90. In five additional steps (+)-preus-sin (2) was synthesized with an overall yield of 19%. After AT-methoxycar-bonylation and oxidation of the alcohol to an aldehyde the alkyl side chain was introduced by a Wittig reaction. 

Bismuth(III) Triflate-Catalyzed Olefin-Epoxide Cyclizations. 53... 

Maruoka K, Murase N, Ooi T, Yamamoto H (1991) A new cyclization of olefinic epoxides by modified organoaluminum reagents via epoxide rearrangement and subsequent intramolecular ene reaction. Synlett 857-858... 

R = R = Me) which are obtained by photooxidation of the corresponding olefin.72 The acid-induced cyclization of the same alcohols has been used they are prepared from coumarins 87,88,185,186 or by base-promoted elimination from epoxides (50).150,164 The acid-catalyzed equilibrium between these alcohols and the corresponding... 

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