2- vinyloxiranes

Allylation under basic conditions. Allylation can be carried out under basic conditions with allylic acetates and phosphates, and under neutral conditions with carbonates and vinyloxiranes. The allylations under neutral conditions are treated separately in Section 2.2.2.1 from those under basic conditions. However, in some cases, allylations of the same substrates are carried out under both basic and neutral conditions to give similar results. These reactions are treated together in this section for convenience. Allylic acetates are widely used for Pd-catalyzed allylation in the presence of bases tertiary amines or NaH are commonly used[6,7,4l]. As a base, basic alumina or ICF on alumina is conveniently used, because it is easy to remove by filtration after the reaction[42]. Allyl phosphates are more reactive than acetates. The allylation with 40 proceeds stepwise. At first allylic phosphate reacts with malonate and then allylic acetate reacts with amine to give 41(43]. 

Allylalion of the alkoxymalonitrile 231 followed by hydrolysis affords acyl cyanide, which is converted into the amide 232. Hence the reagent 231 can be used as an acyl anion equivalent[144]. Methoxy(phenylthio)acetonitrile is allylated with allylic carbonates or vinyloxiranes. After allylation. they are converted into esters or lactones. The intramolecular version using 233 has been applied to the synthesis of the macrolide 234[37]. The /i,7-unsaturated nitrile 235 is prepared by the reaction of allylic carbonate with trimethylsilyl cyanide[145]. 

The reaction of vinyloxiranes with malonate proceeds regio- and stereose-lectively. The reaction has been utilized for the introduction of a 15-hydroxy group in a steroid related to oogoniol (265)(156]. The oxirane 264 is the J-form and the attack of Pd(0) takes place from the o-side by inversion. Then the nucleophile comes from the /i-side. Thus overall reaction is sT -StM2 type, in the intramolecular reaction, the stereochemical information is transmitted to the newly formed stereogenic center. Thus the formation of the six-membered ring lactone 267 from 266 proceeded with overall retention of the stereochemistry, and was employed to control the stereochemistry of C-15 in the prostaglandin 268[157]. The method has also been employed to create the butenolide... 

Regioselective 1,4-azidohydroxylation to give 309 takes place by the reaction of the vinyloxirane 308 with sodium azide[188]. The reaction of the cyclopen-tadiene monoepoxide 310 with sodium azide or purine base offers a good synthetic method for the carbocyclic nucleoside 311(189-191]... 

The cyclic carbamate (oxazoIidin-2-one) 313 is formed by the reaction of phenyl isocyanate (312) with vinyloxirane[I92]. Nitrogen serves as a nucleophile and attacks the carbon vicinal to the oxygen exclusively. The thermodynamically less stable Z-isomer 315 was obtained as a major product (10 I) by the reaction of 2-methoxy-l-naphthyI isocyanate (314) with a vinyloxir-... 

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

The Pd-catalyzed hydrogenolysis of vinyloxiranes with formate affords homoallyl alcohols, rather than allylic alcohols regioselectively. The reaction is stereospecific and proceeds by inversion of the stereochemistry of the C—O bond[394,395]. The stereochemistry of the products is controlled by the geometry of the alkene group in vinyloxiranes. The stereoselective formation of stereoisomers of the syn hydroxy group in 630 and the ami in 632 from the ( )-epoxide 629 and the (Z)-epoxide 631 respectively is an example. 

Organocuprates react rapidly witli adylic balides for acetates), propargyl balides for acetates), and vinyloxiranes, frequently witli u2 regioselectivity. Tbe reaction ordinarily takes place witli oiui fwitli respect to tlie leaving group) steteoclieniistry. 

Racemic terminal vinyloxiranes can also be kinetically resolved with water and the chiral (salen)Co111 complex 21, as already shown in Scheme 9.18 [95]. 

The regioselective ring-opening of vinyloxiranes by nitrogen nucleophiles offers an attractive route to vie-amino alcohols, compounds of much recent interest. As with oxygen nucleophiles, the stereochemistry of the reaction can be controlled by choice of reaction conditions aminolysis of 25, for example, affords anti-amino alcohol 26 in excellent yield and diastereoselectivity (Scheme 9.21) [48, 96, 97], and... 

Additions of oxygen and nitrogen nucleophiles to vinyloxiranes can be achieved with Pd(0) catalysis [103, 104]. Acetate, silanols, amines, sulfonamides, and azide have been used as nucleophiles, and the stereochemical outcome of these additions, where applicable, is normally the result of two consecutive SN2 reactions. This is demonstrated by the additions of NaNHTs to vinylepoxides 29 and 30, affording syn- and anti-amino alcohols 31 and 32, respectively, in good yields and with high diastereoselectivities (Scheme 9.22) [105]. 

Addition of carbon nucleophiles to vinylepoxides is of particular importance, since a new carbon-carbon bond is formed. It is of considerable tactical value that conditions allowing for regiocontrolled opening of vinyloxiranes with this type of nucleophiles have been developed. Reactions that proceed through fonnation of a rr-allyl metal intermediate with subsequent external delivery of the nucleophile, or that make use of a soft carbon nucleophile, generally deliver the SN2 product. In contrast, the Sn2 variant is often the major reaction pathway when hard nucleophiles are employed. In some methods a nucleophile can be delivered selectively at either the Sn2 or SN2 positions by changing the reaction conditions. 

The use of nonstabilized carbon nucleophiles in this reaction has been rare. Recently, however, it was shown that lithium ester enolates participate in Pd-cata-lyzed 1,4-additions to cyclic and acyclic vinyloxiranes, affording the corresponding 6-hydroxy-4-enoates in good yields and with complete regioselectivity [117, 118]. 

Vinyloxiranes can also be converted into P-lactones (Scheme 9.30) [133, 134], Opening of 66 with Fe2(CO)9 resulted in the (7t-allyl)tricarbonyliron derivative 67 in good yield, together with a minor diastereomer (not shown). Oxidative cleavage of 67 then gave 3-lactone 68, which was used as a key intermediate in the preparation of the cholesterol biosynthesis inhibitor 1233A. 

Other methods for the regioselective SN2-opening of vinyloxiranes include intramolecular enolate addition for formation of cyclohexane systems [135, 136] and Friedel-Crafts alkylations [49, 137, 138]. 

In the presence of catalytic amounts of Pd(0), silicon-substituted vinyloxiranes can rearrange into the corresponding ot-silyl- 3,y-unsaturated aldehydes (Scheme 9.34) [151]. Treatment of 80 with Pd(OAc)2 and P(OPh)3 results in the formation of 7t-allylpalladium complex 81. Bond rotation to give 82, followed by migration of the silyl moiety, affords aldehyde 83, which is trapped in situ to provide the Felkin-Anh product 84. The reaction proceeds with retention of configuration and the ee of the starting material is retained in the product. The size of the silicon substituents is critical for the outcome of the reaction, as is the choice of ligands on palladium. 

As an interesting complement to the above technique, vinyloxiranes can be reduced with Sml2 to give the corresponding (E)-allylic alcohol [160]. 

Vinyloxirancs and vinyl acetals constitute a special subset of allylic electrophiles. The product of Sn2 displacement of vinyloxiranes is an allylic alcohol, while the SN2 product from vinyl acetals is a vinyl ether. 

Table 2. Some Examples of SN2 Reactions of Vinyloxiranes and Vinyl Acetals 1...

Chan and Li reported that conjugated 1,3-butadienes were produced in moderate yields when carbonyl compounds reacted with 1,3-dichloropropene and zinc in water (Eq. 8.29).61 The use of 3-iodo-1-chloropropene instead of 1,3-dichloropropene greatly improved the yields. When the reactions were interrupted after their initial allyla-tions, subsequent base treatment of the intermediate compounds produced vinyloxiranes in high yields. Similarly, reactions of carbonyl compounds with 3-iodo-2-chloromethyl-l-propene followed by base treatment produced 2-methylenetetrahydrofurans (Eq. 8.30).62 Thus, the 3-iodo-2-chloromethyl-l-propene served as a novel trimethylene-methane equivalent.63... 

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