Tandem epoxides

Wipf, P. Xu, W. Organozirconocenes in organic synthesis tandem epoxide rearrangement-carbonyl addition. J. Org. Chem. 1993, 58, 825-826. 

Nitriles can react with functionalized oxiranes in a regioselective manner in a tandem epoxide-opening Ritter reaction (Scheme 39) <2005JOC7447>. 

Functionality adjacent to the epoxide can modify its reactivity. For example, 2,3-epoxy sulfides can be converted to a thiiranium species upon treatment with TMS triflate. This intermediate reacts with 0-silyl amides regiospeci-fically to form l-substituted-3-hydroxy-2-thioethers. Simple primary amines undergo polyalkylation, but imines can be used as an indirect amine equivalent <1996T3609>. Nitriles react with functionalized oxiranes in a regioselective manner in a tandem epoxide opening-Ritter reaction (Equation 17) <2005JOC7447>. 

Tandem epoxide or aziridine ring opening by azide/copper catalyzed [3+2] cycloaddition efficient synthesis of 1,2,3-triazolo P-hydroxy or P-tosylamino functionality motif. 

Scheme 2.29 Tandem epoxidation-Henry-O-allgrlation reaction catalysed by a chiral diarylprolinol trime ylsilyl ether and a chiral ammonium salt.

Scheme 3.8 Tandem epoxidation-ring-opening reaction catalysed by a combination of chiral samarium catalysis and palladium catalysis.

Previously we pointed out that the oxidation of alkenes in water allows one-pot multi-step reactions to be carried out involving tandem epoxidation and ring-opening reactions. Further examples are the synthesis of optically active trifluorolactic acid by aqueous nitric acid ring-opening oxidation of (-)-l,2-epoxy-3,3,3-trifluoropropane [19] in the presence of a catalytic amount of copper metal ... 

The same group also realized the tandem epoxidation and ring-opening reaction on Mn(Salen)-based MOF prepared using Lj2 as the organic linker and Zn as the inorganic node [118]. 

A 11011-addition procedure based on a tandem retroaldol/epoxide-opening/cycli-zation sequence has been utilized for the elaboration of the dihydrofuran ring of the reduced furanochroman subunit of phomactin A. The strategy utilizes the O-TBS-protected 3-epoxy-(3 -hydroxy ketone 201. Cleavage with TBAF starts the retro-... 

Abstract This review presents a description of the C-C bond-forming reactions that have emerged in the field of titanocene mediated or catalyzed epoxide opening over the last 5 years or so. The powerful tandem sequences for polycylization will be especially emphasized. 

The Pd-catalysed carbonylation of alkynyl epoxides 60 and alkynyldioxolanones 61 leads to the allenes 62 which can then be converted to the same pyranones through a tandem conjugate addition-cyclisation (Scheme 40) <00JCS(P1)3188>. Carbonylation of allenyl alcohols is catalysed by Ru3(CO)i2 and yields 5,6-dihydropyran-2-ones . 

Scheme 60 Mechanism for titanocene-catalyzed epoxide ring opening and tandem reaction...

McDonald and coworkers studied a series of tandem endo-selective and stereospecific oxacyclization of polyepoxides by reaction with Lewis acid [92-95]. Polyepoxides, such as 50, can be obtained from the epoxidation of triene 49 with ketone 26 (Scheme 8). This cascade cyclization of polyepoxides provides an efficient method to synthesize substituted polycyclic ether structures, which are present in a number of biologically active marine natural products. 

We began these studies with the intention of applying this tandem asymmetric epoxidation/asymmetric allylboration sequence towards the synthesis of D-olivose derivative 63 (refer to Figure 18). As the foregoing discussion indicates, our research has moved somewhat away from this goal and we have not yet had the opportunity to undertake this synthesis. This, as well as the synthesis of the olivomycin CDE trisaccharide, remain as problems for future exploration. Because it is the enantioselectivity of the tartrate ester allylboronates that has limited the success of the mismatched double asymmetric reactions discussed here, as well as in several other cases published from our laboratorythe focus of our work on chiral allyiboronate chemistry has shifted away from synthetic applications and towards the development of a more highly enantioselective chiral auxiliary. One such auxiliary has been developed, as described below. 

Reaction at the C atom of nitronate salts is known with a variety of electrophiles, such as aldehydes (Henry reaction) and epoxides (191-193). Thus the incorporation of the nitro moiety and the cyclization event can be combined into a tandem sequence. Addition of the potassium salt of dinitromethane to an a-haloaldehyde affords a nitro aldol product that can then undergo intramolecular O-alkylation to provide the cyclic nitronate (208, Eq. 2.17) (59). This process also has been expanded to a-nitroacetates and unfunctionalized nitroalkanes. Other electrophiles include functionalized a-haloaldehydes (194,195), a-epoxyaldehydes (196), a-haloenones (60), and a-halosulfonium salts (197), (Chart 2.2). In the case of unsubstituted enones, it is reported that the intermediate nitronate salt can undergo formation of a hemiacetal, which can be acetylated in moderate yield (198). 

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