Vinyl epoxide, synthesis

The Aggarwal group has used chiral sulfide 7, derived from camphorsulfonyl chloride, in asymmetric epoxidation [4]. Firstly, they prefonned the salt 8 from either the bromide or the alcohol, and then formed the ylide in the presence of a range of carbonyl compounds. This process proved effective for the synthesis of aryl-aryl, aryl-heteroaryl, aryl-alkyl, and aryl-vinyl epoxides (Table 1.2, Entries 1-5). 

Table 1.1 Synthesis of aryl-vinyl epoxides by use of chiral sulfide 1 a phosphazene base.

Scheme 9.32 Synthesis of (S)-ibuprofen (69) from vinyl-epoxide 70 Ar = 4- BuC6H4.

The subsequent epoxidation of these in situ formed allylic tertiary alcohols yielded the corresponding syn-e oxy alcohols with high levels of diastereo- and enantioselectivity, thus providing a novel one-pot asymmetric synthesis of acyclic chiral epoxyalcohols via a domino vinylation epoxidation reaction (Scheme 4.17). ... 

Chloro-substituted [Ipc]2BH derivatives have proven useful for enantioselective synthesis of vinyl epoxides.62... 

Danishefsky s total synthesis of 317 and its chlorine free precursor monocillin I 316 features an RCM reaction with a substrate 310 that in addition to a dithiane protective group contains a vinyl epoxide and a diene moiety at... 

Various unsaturated compounds, such as CO2, isocyanates and aldehydes, undergo Pd-catalysed cycloaddition with vinyl epoxides. Reaction of CO2 with 127 affords cyclic carbonates 128 with retention of the configuration at C(3), offering a method of cis hydroxylation of epoxides [66], and has been used for the synthesis of the side-chain unsaturated (—)-exo-brevicomin (129) [67], The tetrahydrofuran 131 was prepared by [3+2] cycloaddition of activated alkenes such as benzylidene malononitrile (130) with vinyl epoxide via Michael addition and allylation [68],... 

Sunay, U. Fraser-Reid, B. Synthetic studies relating to the C1-C9 eastern" half of rosara-micin. Tetrahedron Lett. 1986, 27, 5335-5338. Smith, A. B. Pitram, S. M. Boldi, A. M. Gaunt, M. J. Sfouggatakis, C. Moser, W. H. Multicomponent linchpin couplings. Reaction of dithiane anions with terminal epoxides, epichlorohydrin, and vinyl epoxides efficient, rapid, and stereocontrolled assembly of advanced fragments for complex molecule synthesis./. Am. Chem. Soc. 2003, 125, 14435— 14445. 

The various allylic substitution reactions are illustrated in a synthesis of Tipranavir (11), an HIV protease inhibitor. A palladium-catalyzed opening of a vinyl epoxide set the quaternary stereogenic center (Scheme 22.23). A molybdenum-catalyzed allylic nuclophilic displacement was used to access the benzylioc stereogenic center (Scheme 22.24).153... 

Another version operating under neutral conditions (Scheme 3) uses vinyl epoxides (7) as the source of the i73-allylpalladium complex 8. Here, the alkoxide is generated by opening of the epoxide simultaneously with the formation of the cationic complex. The final compound (9) possesses an alcohol functional group. This variant is very important in the synthesis of carbanucleosides. 

Vinyl epoxides can also be used as substrates for formation of optically active allyl amines catalyzed by the same type of chiral palladium complexes as in Eq. (10). By reaction of simple vinyl epoxides with phthalimide as the nitrogen source in the presence of the chiral palladium complexes as the catalyst, very high ee (> 98 %) and regioselectivity (> 97 %) were obtained [26]. A variety of different applications of the use of the palladium-catalyzed approach for the formation of allyl amines and the use of this in total synthesis has been pursued by several research groups, and further details can be obtained in a review by Trost et al. [19d]. 

As the key precursor towards the realization of 1,7-epoxy cyclononanes and 1,8-epoxycyclodecanes, an 1 l-oxatricyclo[6.2.1.02,6]decane skeleton was constructed by using the Hoffmann [4+3] cycloaddition methodology <07EJO4383>. In Majetich s total synthesis of (-)-salviasperanol, the key step was the trifluoroacetic acid-promoted isomerization of a vinyl epoxide to 2,5-dihydrofuran, whose O-thiocarbamate was removed by radical reaction to produce salviasperanol dimethyl ether <07OL85>. The synthetic route is depicted below. 

In the course of our earlier studies on terpenylboranes we developed a simple transformation of a- into 3-pinene," and a stereoselective synthesis of allylic alcohols by the reduction of vinylic epoxides.12 An extension of these studies to contrathermo-dynamic isomerization of a-thujene, 2- and 3-carene,13 and kinetic resolution of vinylic epoxides by the reduction with terpenylboranes,14 is described. 

SYNTHESIS OF (+)-3(10>CARENE, (+)-SABINENE, AND KINETIC RESOLUTION OF VINYLIC EPOXIDES... 

Analogous reactions of acyclic vinyl epoxides 15 with 4-toluenesulfonyl isocyanate also proceed with complete retention of configuration55. Enantiomerically pure epoxides such as 15b and c are readily available and reductive removal of the 4-toluenesulfonyl substituent from 16 is easily achieved. The transformation of 15c to 2-oxazolidinone 16c was used as the key conversion in a short enantioselective synthesis of acosamine55. 

In studies directed towaids the synthesis of the fungal isonitrile antibiotic isonitrin B (103), a cy-clopentanoid metabolite related to trichoviridine (104), various trialkylsilyl enol ethers were irradiated with propionaldehyde to produce equimolar amounts of stereoisomeric bicyclic oxetanes (105). The corresponding silyl dienol ethers, however, gave little oxetane product owing to preferential diene photopolymerization. The use of vinyl epoxide derivatives such as (106), however, offers a possible access to the epoxycyclopentanoid system with simultaneous control of the face selectivity of the photoaddition by the epoxide moiety. 

Trost and Scanlan reported a Pd-catalyzed condensation of a vinyl epoxide 75 and an allyl sulfone 76 in the presence of dppf under neutral conditions [231]. This alkylation allows a room temperature entry to a basic indolizidine ring system as a step towards the synthesis of (+)-aj//o-Pumiliotoxin 339B [232], The modification of allylic alkylations by condensation of a diene 77 with a pronucleophile 78 also leads to C-C bond formation at the allylic position in both 1 1 (79 and 80) and 2 1 (81 and 82) products [233]. Reactions between ketene silyl acetals 83 with allyl... 

Previous preparations by Scolastico were based on the Strecker synthesis of aminonitrile and lacked steroselectivity [74,75]. More recently, two formal syntheses were reported from the same ketone 71. In Rama Rao s synthesis (Scheme 11.19) [76], 71 was condensed with vinyl magnesium bromide to give the tertiary alcohol 72 as a single isomer. This compound was then transformed into the vinyl epoxide 73 that, under palladium catalysis, reacted with 4-methoxyphenyl isocyanate to produce the oxazohdinone 74 with retention of its configuration. The remainder of the synthesis consisted of heterocycle opening and adjustment of the oxidation level to provide the lactone 75. Excision of two carbons was necessary to form the known aldehyde 76, previously transformed into myriocin [74]. 

Rama Rao, A V, Gurjar, M K, Devi, T R, Kumar, K R, A formal synthesis of a novel immunosuppressant ISP-1 stereocontrolled Pd(0) catalyzed cis hydroxyamination of carbohydrate derived vinyl epoxide. Tetrahedron Lett., 34, 1653-1656, 1993. 

Palladium-catalyzed nucleophilic substitution reactions of allylic substrates have become useful in organic synthesis. As allylic substrates, allyl alcohols, halides, carboxylates, phosphates or vinyl epoxides can be utilized. 

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