Epoxides Lewis acid-mediated

Oxindole 89 was cleanly demethylated upon treatment with boron tribromide. The resulting oxindole 90 was subjected to the prenylation conditions, and the desired alkylated product 91 was obtained in 52% yield. The epoxidation/Lewis acid-mediated cyclization proved to be successful on this substrate. The epoxide product was directly treated with SnCl4 in THF to provided the desired 92. When oxindole 92 was treated with NaBHt (1.6 equivjand BF3 OEt2 (3.5 equiv) in THF, the desired 93 was obtained. The indole 93 was treated with TBDMSC1 and imidazole in DMF, to provide the required O-silylated indole, which was easily converted to the gramine 94 through the well known Mannich procedure. 

A number of the reactions discussed above were used in a synthetic sequence. Friedel Crafts acylation of (98) gives (99) after isomerization of the diene geometry using sodium methoxide. Bromination of aTMS-enol ether, formed from (99), with DBA was nonstereospecific however, the isomers were readily separated (Scheme 159). The pure a-bromoketone is stereospecificaUy methylated and transformed into an epoxide. Lewis acid mediated isomerization of the epoxide affords an optically pure ketone (100). 

Additional heterocyclic ring systems, such as benzofurans [125], dihydropyrroles and dihydroazepines [41], piperidines and dihydropyrimidines 36 [126], and fused oxazole derivatives [127], have been described (Eq. 7). The formation of epoxides and aziri-dines, formally emanating from ylides, was recently reported by Doyle et al. [77]. Rho-dium(II)-catalyzed isomiinchnone cycioaddition followed by Lewis acid-mediated ring opening has been used as an entry into the protoberberine azapolycyclic ring structure [128]. 

Lewis acid-mediated epoxide rearrangement followed by 1,2-addition. 

In the following scheme, the benzo[Z>]furan core of ( )-frondosin B was built up by the palladium-catalyzed quinone reduction, followed by Lewis acid-mediated benzo[Z>]furan formation <07OL3837>. In the total synthesis of bisabosquals, the core structure of benzo[ ]furan was constructed by an epoxide-ring opening reaction <07T10018>. 

Scheme 4 depicts the remainder of our total synthesis. The acid (5) was subjected to RedAl reduction to give the hydroxymethyl intermediate (6) in 99 % yield, which was then protected as the terf-butyldiphenylsilyl ether (7) under standard conditions (96 %). Silicon-mediated fragmentation of the acetonide (7) was carried out under Lewis acid-mediated conditions (BF, OEtj) to fiimish allylic alcohol (8) in 96 % yield. Sharpless epoxidation provided (9), followed by a diastereosclective diimide reduction of the remaining oleHn, to give the epoxyalcohol (10) in satisfactory yield, uid as exclusively one diastereoisomer. 

A novel stereoselectivity is observed in the Lewis acid mediated S 2 -type reactions of an epoxy-cycloalkene and methylating reagents. Syn attack occurs with MeLi-LiC104 in high selectivity, and exclusive anti attack with MeCu-MesAl. Chelation of MeLi to the epoxide or to the epoxide-LiC104 complex is suggested for the former, while attack of MeCu on the MesAl-coordinated epoxide from the less hindered site is presumed for the latter. The use of MeLi gives a mixture of several compounds (Scheme 20)." ... 

In the laboratory of P.G. Steel, a five-step synthesis of ( )-epiasarinin from piperonal was developed. The key steps in the sequence involved the Darzens condensation, aikenyi epoxide-dihydrofuran rearrangement and a Lewis acid mediated cyclization. The desired vinyl epoxide intermediate was prepared by treating the solution of ( )-methyl-4-bromocrotonate and piperonal with LDA, then quenching the reaction mixture with mild acid (NH4CI). 

Indoles react with epoxides and aziridines in the presence of Lewis acids (see section 17.5 for reaction of indolyl anions with such reactants) with opening of the three-membered ring and consequent 3-(2-hydroxyalkylation) and 3-(2-amino-alkylation) of the heterocycle. Both ytterbium triflate and phenylboronic acid are good catalysts for reaction with epoxides under high pressure " silica gel is also an effective catalyst, but slow at normal pressure and temperature." Lewis acid-mediated reaction with aziridines can be catalysed by zinc triflate or boron trifluoride.More reactive alkylating electrophiles react at lower temperatures, at room temperature with dimethylallyl bromide for example. ... 

Naruta and coworkers developed a method for the synthesis of an an-thracyclinone tetracyclic moiety based on a Lewis acid-mediated tandem Michael-Diels-Alder reaction of acryloyl quinone with pentadienyltins [165]. Subsequent enantioselective Sharpless epoxidation led to an enantiopure intermediate that was converted into ll-deoxydaunomycinone [166]. In more recent work, they obtained enantiomerically pure 7,ll-deoxydaunomycinone (176) and its analogues by the above strategy using the enantiopure penta-dienyltin derivative 171 [167], which was obtained in six steps from racemic ester 167 [168] (Scheme 34). 

Many additional applications of semipinacol rearrangements on a-hydroxy epoxides have been developed,and these reactions have found use in complex molecule synthesis. For example, a-hydroxy epoxide 47 underwent a Lewis acid-mediated semipinacol ring expansion to set the challenging in-out intrabridgehead stereochemistry of the ingenol core. ... 

This book chapter is limited to Lewis acid-mediated reactions, and does not discuss the important field of Lewis base-mediated allylations, nor does it describe the reactions of allylsilanes with other electrophiles such as epoxides, imines, and allyl-X (X = -Cl, -OR, -OAc). The SaJcurai reaction has been covered under different forms in reviews focusing on The Stereochemistry of the Sakurai reaction , Intramolecular Addition Reactions of Allylic and Propargylic Silanes ," Selective Reactions Using Allylic Metals , Catalytic Enantioselective Addition of Allylic Organometallic Reagents to Aldehydes and Ketones , and Modem Carbonyl Chemistry . ... 

Jamison employed an entto-selective Lewis acid-mediated epoxide cascade reaction in the total synthesis of armatol A (157 Scheme 4.33) [68]. The key transformation was the BFj OEtj-mediated isomerization of triepoxide 158. This resulted, upon acylation, in the formation of fused tricycle 159. Also of note, a bromonium ion-mediated epoxonium ion-forming reaction was used to form the isolated oxepane unit en route to the completion of the synthesis of the natural product. 

For Reviews on the Lewis acid mediated rearrangement reactions of epoxides, see (a) Parker, R.E., Isaacs, N.S. (1959) Chemical Reviews, 59,... 

Scheme 28 Lewis acid-mediated epoxide-opening cyclization to D ring of phorboxazole A [57]...

A Lewis acid-mediated epoxide opening cascade has been reported to provide the oxygenated core of pactamycin (Scheme 67). ... 

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