Aryl epoxides

A Baylis-Hillman type product has been obtained through a ring-opening reaction of an epoxide with an allenoate <06OL2771>. The reaction of MgL, with ethyl propiolate provides the iodo allenoate 32. This nucleophile reacts with an aryl epoxide to provide the homoallylic alcohol 33. The Z iodide is the major product formed. 

A much more elaborate synthesis of 4-aryl-2-(benzyloxy)carbonyl-3-hydroxy tetrahydrofurans 88 from aryl epoxides requires the use of benzyl diazoacetate. This methodology can now be extended to a highly stereoselective synthesis of chiral tetrahydrofurans starting from optically active epoxides. The mechanism is believed to involve a Williamson-type cyclization as illustrated below <00TL8059>. 

More recent developments in the field of the Pirkle-type CSPs are the mixed r-donor/ r-acceptor phases such as the Whelk-Of and the Whelk-02 phases.The Whelk-Of is useful for the separation of underiva-tized enantiomers from a number of families, including amides, epoxides, esters, ureas, carbamates, ethers, aziridines, phosphonates, aldehydes, ketones, carboxylic acids, alcohols and non-steroidal anti-inflammatory drugs.It has been used for the separation of warfarin, aryl-amides,aryl-epoxides and aryl-sulphoxides. The phase has broader applicability than the original Pirkle phases. The broad versatility observed on this phase compares with the polysaccharide-derived CSPs... 

Stereoselective addition of allyl metal reagents to various functionalities is an important reaction in organic synthesis [32, 33]. The allylation of epoxides and aziridines with allyltin reagent is catalyzed by Lewis acids. Even though many Lewis acids have been reported to catalyze this reaction, Bi(OTf)3 is distinct because it avoids the formation of byproducts and is also environmentally more compatible. It catalyzes the reaction of aryl epoxides with tetraallyltin to afford the corresponding homoallyllic alcohol [34]. 

Laser flash photolysis of 18 (Ar = -N02C6H4) led to the formation of the aryl chlorocarbene detected at 320 nm. In the presence of acetone, a new species was observed at X = 590 nm that was assigned the structure of carbonyl ylide 19. The ylide, formed by attack of acetone on the carbene, was shown to be irreversible, where the lifetime of the ylide (1.35 ps, fecyciization = 7.40 x 10 s ) was controlled by cyclization to the aryl epoxide 22. The rate constant for the cycloaddition of substituted benzaldehydes to produce dehydrodioxolane (21) was determined experimentally (e.g., p-ClPhCHO=6.16 x 10 M s ). 

C-C Cleavage in Epoxides. Radical cations generated by photoinduced electron transfer from epoxides (130) or aziridlnes (131) also ring open, giving oxidative products in the presence of oxygen. For example, dicyanoanthracene sensitizes the conversion of aryl epoxides to ozonides, eq. 48,... 

A regioselective and highly syn-stereoselective catalyst-free intermolecular alkylation of aryl borates with aryl epoxides under mild, neutral conditions has been reported.27 The reaction of /ra .s-stilbene oxide with tri(3,5-dimethylphenyl)borate gave a 38% yield (>95% syn) of the C-alkylated product (13), easily separated from (g) the O-alkylated product(s). Triflic anhydride has been used to activate enones to nucleophilic attack by electron-rich arenes in the presence of a sterically hindered base.28 Resorcinol dimethyl ether, for example, reacted with cyclohex-2-en-l-one to... 

Transition metal mediated cross couplings of epoxides have remained relatively unexplored, with only a few examples of this potentially useful reaction reported in the literature. A recent report details the Suzuki-Miyaura cross-coupling of epoxides <07JOC3253>. The reaction of aryl epoxides with arylboronic acids under Suzuki-Miyaura coupling conditions provides the coupled product in good yields. Careful monitoring of the reaction is essential to avoid Pd-catalyzed rearrangement of the epoxides. 

Aluminum reagents have rarely been used to open epoxides. A recent report details the use of vinyl aluminum reagents prepared in situ to open aryl epoxides <07OL4753>. Treatment of ethyl propiolate with DIBAL provides an intermediate vinyl aluminum reagent 25, which can then react with styrene oxide to provide homoallylic alcohol 26. 

This route can be used to generate vinyl oxiranes, useful intermediates for organic synthesis <2000TL7309, 2002JOC9083, 2003JOC2060>. Aryl epoxides have been made and have been used as intermediates in the context of total synthesis venture <2004T9725>. 

Various pharmaceuticals including 2-aryI propionic acids, aryl epoxides, sulphoxides. alcohols, amides and esters, thalidomide, nicardipine, isradipine. mephenytoin. nirvanol. cyclandelate, bendroflumethiazide. hupivicaine, tolperisone. proglumide. tropicamide and indapamidc... 

Reduction of epoxides-1 Styrene oxide and similar aryl epoxides undergo rapid anti-Markownikov opening when reduced with diborane in the presence of boron... 

An alternative diversity-oriented approach for the synthesis of structurally diverse catechins (48), involved the thiourea/AuCl3/AgOTf-catalyzed annulations of aryl epoxides (47) (Scheme 6), with special emphasis on the development of a synthesis protocol to the anti-HIV compound, 8-C-ascorbylepigallocatechin (49). Additionally, Liu etal contains a comprehensive list of references related to the syntheses of various catechins and their analogues. 

Scheme 6 Synthesis of racemic catechins via thiourea/AuCis/AgOTf-catalyzed cycloalkylation of aryl epoxides (47).

These reagents can also effect regiosclectivc opening of aryl epoxides. 

Epoxide cleavage. Carboxylic acids are obtained from this reaction. It shows chemoselectivity in that alkenes and alcohols are inert. Bismuth(III) acetate and oxide are not effective. In aryl epoxides, the presence of electron-donating groups favor the oxidation. ... 

Aryl epoxides undergo rearrangements to aldehydes and ketones in the presence of Lewis acid catalysts. For example, the cyclopentene oxide derivative 80 opens up to the more stable benzylic carbocation, which then provides the cyclopentanone derivative 82 via 1,2-methyl migration in 93% yield <01T815>. A similar rearrangement (83 84) has been shown to... 

Chiral aryl epoxides are converted into hydroxy-protected chiral a-hydroxy aryl ketones with complete retention of the chiral center and good regioselectivity by treatment with a combination of DMSO and TMSOTf (eq 93). Other reagent combinations such as DMSO/BF3 OEt2 or DMSO/TfOH lead to lower yields of the desired alcohols. ... 

Carbenes are also generated when aryl epoxides are photolyzed (entry 4, Scheme 8.1). The other product formed is a carbonyl compound. The photodecomposition of epoxides is not a single-step process highly colored intermediate species... 

A similar approach for an improved in vivo cofactor recychng was published by Itoh and coworkers [20]. They combined a styrene monooxygenase (SMO) from Rhodococcus sp. [21] and an ADH from Leifsonia sp. for the efficient synthesis of chiral aryl epoxides starting from olefins (Scheme 3.4). They tested 19 different olefins and could convert substrates in titers ranging from 10 mM for very polar to 200 mM for nonpolar substances. 

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