Epoxides from allylic alcohols

AUyl transfer reactions, 73, 1 Allylic alcohols, synthesis from epoxides, 29, 3 by Wittig rearrangement, 46, 2 Allylic and benzylic carbanions, heteroatom-substituted, 27, 1 Allylic hydroperoxides, in... 

N,O-acetal intermediate 172, y,<5-unsaturated amide 171. It is important to note that there is a correspondence between the stereochemistry at C-41 of the allylic alcohol substrate 173 and at C-37 of the amide product 171. Provided that the configuration of the hydroxyl-bearing carbon in 173 can be established as shown, then the subsequent suprafacial [3,3] sigmatropic rearrangement would ensure the stereospecific introduction of the C-37 side chain during the course of the Eschenmoser-Claisen rearrangement, stereochemistry is transferred from C-41 to C-37. Ketone 174, a potential intermediate for a synthesis of 173, could conceivably be fashioned in short order from epoxide 175. 

Previous syntheses of terminal alkynes from aldehydes employed Wittig methodology with phosphonium ylides and phosphonates. 6 7 The DuPont procedure circumvents the use of phosphorus compounds by using lithiated dichloromethane as the source of the terminal carbon. The intermediate lithioalkyne 4 can be quenched with water to provide the terminal alkyne or with various electrophiles, as in the present case, to yield propargylic alcohols, alkynylsilanes, or internal alkynes. Enantioenriched terminal alkynylcarbinols can also be prepared from allylic alcohols by Sharpless epoxidation and subsequent basic elimination of the derived chloro- or bromomethyl epoxide (eq 5). A related method entails Sharpless asymmetric dihydroxylation of an allylic chloride and base treatment of the acetonide derivative.8 In these approaches the product and starting material contain the same number of carbons. 

Allylic alcohols can also be obtained from epoxides by ring opening with a selenide anion followed by elimination via the selenoxide (see Section 6.8.3 for discussion of selenoxide elimination). The elimination occurs regiospecifically away from the hydroxy group.116 117 118... 

The oxygen that is transferred to the allylic alcohol to form epoxide is derived from tert-butyl hydroperoxide. The enantioselectivity of the reaction results from a titanium complex among the reagents that includes the enantiomerically pure tartrate ester as one of the ligands. The choice whether to use (+) or (-) tartrate ester for stereochemical control depends on which enantiomer of epoxide is desired. 

Altylic alcohols from epoxides. Reaction of T with epoxides and then DBN gives reasonable yields of allylic alcohols as the t-butyldimethylsilyl ether. 

Cyclization of allylic alcohols to form epoxides has been particularly problematical, and the reactions have been more of mechanistic than of synthetic interest. For reactions conducted under basic conditions, it is possible that epoxide formation involves initial halogen addition followed by nucleophilic displacement to form the epoxide. Early examples of direct formation of epoxides from allylic alcohols with sodium hypobromite," bromine and 1.5 M NaOH,12 and r-butyl hypochlorite13 have been reviewed previously.fr Recently it has been shown that allylic alcohols can be cyclized effectively with bis(jym-collidine)iodine(I) perchlorate (equation 3).14 An unusual example of epoxide formation competing with other cyclization types is shown in equation (4).15 In this case, an allylic benzyl ether competes effectively with a -/-hydroxyl group as the nucleophile. 

Compatibility of asymmetric epoxidation with acetals, ketals, ethers, and esters has led to extensive use of allylic alcohols containing these groups in the synthesis of polyoxygenated natural products. One such synthetic approach is illustrated by the asymmetric epoxidation of 15, an allylic alcohol derived from (S)-glyceraldehyde acetonide [59,62]. In the epoxy alcohol (16) obtained from 15, each carbon of the five-carbon chain is oxygenated, and all stereochemistry has been controlled. The structural relationship of 16 to the pentoses is evident, and methods leading to these carbohydrates have been described [59,62a]. 

The epoxy alcohol 47 is a squalene oxide analog that has been used to examine substrate specificity in enzymatic cyclizations by baker s yeast [85], The epoxy alcohol 48 provided an optically active intermediate used in the synthesis of 3,6-epoxyauraptene and marmine [86], and epoxy alcohol 49 served as an intermediate in the synthesis of the antibiotic virantmycin [87], In the synthesis of the three stilbene oxides 50, 51, and 52, the presence of an o-chloro group in the 2-phenyl ring resulted in a lower enantiomeric purity (70% ee) when compared with the analogs without this chlorine substituent [88a]. The very efficient (80% yield, 96% ee) formation of 52a by asymmetric epoxidation of the allylic alcohol precursor offers a synthetic entry to optically active 11 -deoxyanthracyclinones [88b], whereas epoxy alcohol 52b is one of several examples of asymmetric epoxidation used in the synthesis of brevitoxin precursors [88c]. Diastereomeric epoxy alcohols 54 and 55 are obtained in combined 90% yield (>95% ee each) from epoxidation of the racemic alcohol 53 [89], Diastereomeric epoxy alcohols, 57 and 58, also are obtained with high enantiomeric purity in the epoxidation of 56 [44]. The epoxy alcohol obtained from substrate 59 undergoes further intramolecular cyclization with stereospecific formation of the cyclic ether 60 [90]. 

A limited number of allylic alcohols of the (2,3Z)-disubstituted type have been subjected to asymmetric epoxidation. With one exception, the C-2 substituent in these substrates has been a methyl group, the exception being a f-butyl group [38]. The (3Z)-substituents have been more varied, as illustrated by structures 61-64, which show the epoxy alcohols derived from the corresponding allylic alcohol substrates. 

Asymmetric epoxidation of allylic alcohols is a very reliable chemical reaction. More than a decade of experience has confirmed that the Ti-tartrate catalyst is extremely tolerantof structural diversity in the allylic alcohol substrate for epoxidation yet is highly selective in its ability to discriminate between the enantiofaces of the prochiral olefin. Today the practitioner of organic chemistry need provide only the allylic alcohol to perform the reaction. All other reagents and materials required for the reaction are available from supply houses and usually are sufficiently pure as received to be used directly in the asymmetric epoxidation process. [When purchasing f-butyl hydroperoxide in prepared solutions, however, the more concentrated 5.5-M solution in isooctane (2,2,4-trimethylpentane) should always be chosen over the 3.0-M solution.] If the considerations presented in this chapter are observed, with attention to the moderately stringent technique outlined, no difficulty should be encountered in performing this reaction. 

In the kinetic resolution of secondary allylic alcohols hy means of the Sharpless epoxidation (Figure 3.39), the ee value of the epoxy alcohol formed does not quite reach the ee value of the unreacted allyhc alcohol. The reason might be deduced from the epoxidation exemphfied in Figure 3.40. Until 50% conversion is reached it is almost only the reactive enantiomer of the a-substituted crotyl alcohol that undergoes epoxidation. This is not only a very rapid, hut a highly diastereoselective reaction as well, yielding a 98 2 mixture of the anti- and syn-epoxy alcohol. Epoxidation of the unreactive enantiomer of the a-substituted crotyl alcohol is also observed until 50 % conversion is reached, but only to a very minor extent. The result is most... 

Metals that are capable of 2e redox changes, typically main group elements and 4d and 5d transition metals, can give heterolysis of a peroxide to form a diamagnetic oxidant that may avoid the radical pathways seen in the case of equation (14-15). O atom transfer to the substrate is possible in this way. Sharpless epoxidation provides an excellent example. In this case rBuOOH is the primary oxidant, Ti(i-OPr)4 is the catalyst precursor and a tartrate ester is the ligand that induces a high ee in the epoxy alcohol formed from an allylic alcohol. This reaction has been successfiiUy developed on an industrial scale. 

Allyl silanes react with epoxides, in the presence of Bp3 OEt2 to give 2-allyl alcohols.The reaction of a-bromo lactones and CH2=CHCH2Si(SiMe3)3 and AIBN leads to the a-allyl lactone.On the other hand, silyl epoxides have been prepared from epoxides via reaction with iec-butyllithium and chlorotri-methylsilane. ° a-Silyl-A-Boc-amines were prepared in a similar manner from the A-Boc-amine. " Arylsilanes were prepared by reaction of an aryl-lithium intermediate with TfOSi(OEt)3. In the presence of BEs etherate, allyl silane and a-methoxy A-Cbz amines were coupled. Benzyl silanes coupled with allyl silanes to give ArCHa—R derivatives in the presence of VO(OEt)Cl2 " and allyltin compounds couple with allyl silanes in the presence of SnCl4. Allyl silanes couple to the a-carbon of amines under photolysis conditions. 

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