Epoxy triflates

The monoanions of 1,3-dicarbonyl compounds react smoothly with the cis-oriented epoxy triflate 1 to give the intermediate I which, after further base treatment, leads to a dihydrofuran system [20] (Scheme 7). After treatment of 1 with dianions of 1,3-dicarbonyl compounds, tetrahydrofurylidine formation is observed under kinetic conditions [20] (Scheme 7). 

Butanolides are ubiquitous subunits of a large number of bioactive com-poimds. Epoxy triflate sugars 1 and 2 open an easy access to selected polysubstituted chiral butanolides [36,37], by a two-step sequence. The first step is displacement of the triflyl group of 1 and 2 under extremely controlled conditions with a very reactive enolate of ferf-butyl acetoacetate followed by cycHzation under acid catalysis, which furnished 45 and 46 [36] (Scheme 9). 

For the preparation of the quinoxaline derivatives, the epoxy triflates 1 and 2 are allowed to react with o-phenylenediamine or 4,5-dichloro-l,2-diaminobenzene in THF at room temperature to yield, after conventional workup, the chiral quinoxahne derivatives 104,105 and 106,107, respectively (Scheme 21). 

Reaction of the epoxy triflates 1 and 2 with the dianion of 1,2-dihydroxy-benzene or 2,3-dihydroxynaphthalene at room temperature yields the corresponding chiral benzodioxins 108 and 110 or the naphthodioxins 109 and 111, respectively (Scheme 22). 

Epoxy triflates (e.g., 1, 2, 127-129) are also useful synthons for a simple and efficient route to cyclic trithiocarbonates (e.g., 126-134) [95]. Formation of these trithiocarbonates involves the addition of a red aqueous solution of Na2CS3 [96] to a stirred solution of epoxytriflate. The nucleophilic displace-... 

Several deoxypentoses linked through C-3 or C-4 to L-alanine residues have been synthesized from epoxy-triflates. As exemplified in Scheme 4, the /S-L-rjiifi-derivative (14) underwent initial triflate displacement to epoxide (15). Irreversible isomerization of this 2,3-epoxide to a 3,4-epimine and subsequent hydrolysis of this gave predominantly the 3-amino-3-deoxy-L-xylose derivative (le)." " ... 

Reaction of a number of methyl 2,3-di-Q-benzyl aldohexopyranosides with phenylchlorosulphate - sodium hydride gave, depending on the conditions used, primary phenylsulphates or 4,6-cyclic sulphates7 The formation of cyclic sulphates from epoxy triflates and of cyclic sulphites from vicinal ditosylates are referred to in Section 3 of this Chapter. 

Branch at C-4. - The addition of the anion derived from tert-hvdyX acetoacetate to the epoxy-triflate 51 affords the bicyclic derivative 52 by a process in which the triflate is first displaced with inversion of configuration followed by... 

The isomeric epoxy triflates 153 and 157 undergo triflate displacement-epoxide opening with the dianion of methyl propanoyl acetate. Reaction of 153 generates the epimeric bicyclic tetrahydrofurans 154 and 155, subsequent treatment with triflic acid leading to isomerization about the alkene bond to a mixture of 154-156. Isomeric 157 under similar conditions gives 158 and 159, with triflic acid catalysis leading to some of the alkene isomers 160 along with 158 (Scheme 32). ... 

The reactivity of epoxides can be modified by various proximal functionality. For example, 2,3-epoxy sulfides 118 are converted to the corresponding TMS-thiiranium species 119 upon treatment with TMS triflate. This intermediate reacts with O-silyl amides regiospecifically to form l-substituted-3-hydroxy-2-thioethers (e.g., 120). Simple primary amines undergo polyalkylation, but imines can be used as an indirect amine equivalent <96TET3609>. 

Four TES ethers were cleaved in the final step of an approach to N1999-A2, a member of the highly unstable enediynes.20 After low temperature dehydration of 17.1 via its triflate [Scheme 4.17], deprotection was implemented by treatment with trifluoroacetic acid in aqueous THE at 0 °C to give the target epoxy-dienediyne 17.2 in 45% yield for the two steps. rtrf-Butyldimethytsilyl ethers could not be removed without total destruction of the molecule. 

So far the reactivity of epoxides has involved their use as an electrophile. However, oxtranyl anions can serve as functionalized nucleophiles in their own right. Thus, the sulfonyl substituted epoxide 107 can be deprotonated with -butyllithium to provide a stabilized anion which engages in facile Sn2 reaction with triflate 108 <03JOC9050>. Other examples of such stabilized epoxide anions include those derived from oxazolinyloxiranes (e.g., 110), which react with nitrones to provide the spirotricyclic heterocycles of type 112, Hydrolysis provides the epoxy amino acids 113, in which the carboxylic acid moiety was provided by the oxazoline nucleus and the amine functionality was derived from the nitrone <03OL2723>. A recent report has demonstrated that oxiranyl anions can also be stabilized by the amide functionality <03H(59)137>. 

Reaction of Sulfonyl-Stabilized Oxiranyllitbiums. Reaction of sulfonyl-stabilized oxiranyllitbiums with primary alkyl halides gives acceptable yields of products. More reactive alkyl triflates give generally better yields but, due to the instability of oxiranyl-lithiums, yields are often not reproducible when electrophiles are added to a solution of the preformed oxiranyllitbiums. It is recommended that the alkylation reaction be carried out by an in situ trapping method. Treatment of a solution of epoxy sulfone (1.0 equiv) and triflate (1.5 equiv) in THE-DMPU (or HMPA) at — 100 °C under argon with n-BuLi (1.0 equiv) followed by stirring... 

Related Reagents. Optically active trisubstituted sulfonyl-stabilized oxiranyllithiums can be generated by deprotonation of the corresponding epoxy sulfones (eq 9). Due to the diminished reactivity of the reagents by steric hindrance, the reaction with triflates requires HMPA to obtain a high yield of product (eq 10). ... 

Tin(n) triflate mediated cross aldol reactions between a-bromo ketone (124 Scheme 56) and aldehydes afford iyn-a-bromo-P-hydroxy ketones (125) with high stereoselectivity. The resulting halohydrins are converted to the corresponding (Z)-2,3-epoxy ketones (126). Chiral aldehyde (127) reacts with lithium alkynide (128) followed by mesylation and base treatment to give chirally pure ( )-epoxide (129). The initially formed alkoxide anion should be trapped in situ by mesylation, otherwise partial racemization takes place owing to benzoate scrambling (Scheme 56). ... 

Bickley, J. E., Hauer, B., Pena, P. C. A., Roberts, S. M., Skidmore, J. The semi-pinacol rearrangement of homochiral epoxy alcohols catalyzed by rare earth triflates. J. Chem. Soc., Perkin Trans. 1 2001,1253-1255. 

The high efficiency of the present precursor 2 is demonstrated by comparison with a similar precursor, 2-(trimethylsilyl)phenyl triflat (4), which generates benzyne under mild conditions (room temperature and neutral).7 Benzyne precursor 2 gives the adduct, 1,4-epoxy-1,4-dihydronaphthalene 3, quantitatively in the reaction with furan, while the reaction of benzyne precursor 4 under the same conditions leads to a lower yield of adduct 3 and needs longer reaction time. 

Stereoselective epoxidation of enoates. The final step in the synthesis of (+)-aphidicolin (4) requires a stereoselective conversion of the cyclic norketone (I) to a Wol,2-diol, >C(0H)-CH20H. Methylcnation of the ketone followed by a Sharpless asymmetric dihydroxylation provides a 1 1 mixture of epimcric 1,2-diols. Reaction with a chiral oxaziridinc also provides a 1 1 mixture of cpimcric epoxides. The transformation is effected successfully by conversion of the ketone to the enol triflate, which is converted to the enoate (2) by Pd-catalyzed carbonylation in methanol (13,234). Epoxidation of 2 with m-CPBA in buffered CH2CI2 with a radical scavenger (4,85-86) results in a single epoxy ester (3) in 90% yield. This product is reduced with lithium aluminum hydride (excess) to aphidicolin (4) in 67% overall yield from the ketone 1. 

In order to craft the lactone ring, 38 was oxidized to 40 under Swem conditions in a prelude to intramolecular 1,4-addition of the hemiacetal anion [20] formed via nucleophilic attack by methoxide ion at the aldehyde site. With the availability of acetal 41, it became necessary to consider carefully whether to elaborate the epoxy lactone segment in advance of, or subsequent to, introduction of the a,p-unsaturated ester subunit. Since the latter option was considered more workable, 41 was transformed into the enol triflate and subjected to palladium(II) catalyzed methoxycarbonylation [21]. This methodology allowed for proper homologation of 42 to 43, and subsequent conversion to 44, in totally regiocontrolled fashion. 

P-Siloxyaldehydes. Chiral epoxy alcohols are readily available (e.g., by Sharpless epoxidation of allylic alcohols). Their transformation via a stereoselective rearrangement-silylation induced by the silyl triflate and i-Pr2NEt opens a new way to protected aldols. 

Epoxy enynes. The coupling of enol triflates with epoxyalkynes is catalyzed by Agl-PdCPPhj) (5 examples, 52-90%). 

Epoxides can also be converted to 1,3-dioxolanes by treatment with acetone in the presence of catalytic amounts of bismuth(lll) salts, with yields ranging from 87-99%. For example, the epoxy allyl ether 98 provided the dioxolane 99 in 97% yield using bismuth triflate as the catalyst <01SC3411>. When simple epoxides are treated with Aw(triphenylphosphine)-iminium cobalt tetracarbonyl (PPN-Co(CO)4) under Lewis acid catalysis, a carbonyl insertion reaction provides p-lactones regioselectively in good to high yields. The carbonylation occurs selectively at the unsubstituted position, and the reaction is... 

SUylated aldol adducts can be reached by using a nonaldol rearrangement promoted by treatment of bulky epoxy bis-silyl ethers with TMSOTf/i-Pr2NEt in methylene chloride at —50 °C (eq 95).Bulky mesylated epoxy silyl ethers also undergo this transformation however, a silyl triflate-promoted Payne rearrangement was observed as a side reaction depending on the stere ochemistry of the starting epoxide. 

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