Allyl from ketal

The routes leading from lactone A have the advantage of a chiral source of starting materials. With the two chiral centers at C24 and C25 set, the problem reduces down to elaborating the B ring with the appropriate substituents. An early solution was provided in an unusual cyclization of the B ring via an intramolecular Michael addition to the unsaturated aldehyde formed from a nitrile oxide 1,3-dipolar cycloaddition to the allyl methyl ketal of lactone A [76]. This clever use of relative stereocontrol provided by the highly constrained and predictable transition states of both key reactions unfortunately resulted in a low yield. A more conventional approach conceptualized the addition of a sulfoxide [77] to 2 to yield a masked diol-ketone precursor which cyclizes under acidic catalysis. Elimination of the sulfoxide permitted the introduction of the hydroxy substituent at C19 of the spiroketal. 

The Claisen rearrangement of vinyl allyl ethers is a powerful reaction for the preparation of yS-unsaturated carbonyl compounds. The regioselectivity of the ketal version of this reaction has been studied, the results aiding the understanding and prediction of products formed from ketals of unsymmetrical ketones [equation (34)]. The allyl vinyl ether may also be formed by proto-... 

A variety of conjugated dienones are reduced by lithium-ammonia, presumably via dienyl carbanions analogous to the allyl carbanions encountered in enone reductions. Cross-conjugated l,4-dien-3-ones afford 4-en-3-ones as the major reduction products, indicating that the cyclohexadienyl carbanion (55) protonates largely at C-1. Some protonation at C-5 does occur as shown by examination of the NMR spectrum of the crude reduction product derived from the 17-ethylene ketal of androsta-l,4-diene-3,17-dione. The 17-ethylene ketal of androst-4-ene-3,17-dione is formed in 75%... 

STEREOCONTROLLED PREPARATION OF 3-ACYLTETRAHYDROFURANS FROM ACID-PROMOTEO REARRANGEMENTS OF ALLYLIC KETALS (2S,3S)-3-ACETYL-8-CARBOETHOXY-2,3-DIMETHYL-1-OXA-8-AZASPIRO[4.5] DECANE... 

The reaction is 100% stereoselective and affords 69 as a unique stereomer with the (/f)-configuration at C-6, assigned by X-ray analysis. Consequently, the configuration at C-6 results from the well-known chair transition state model for the (Z)-O-allyl enol 68 in which the aUyl unit is on the opposite side to the isopropylidene ketal at C3-C4 and reacts on the Si face of the trisubstituted carbon-carbon double bond. Such a transition state leads to the sole (/ )-configuration in 69. 

The first example of enantioselective allylzincation of an alkene was also reported for the cyclopropenone ketal 78 as substrate. The chiral allylzinc complex 135 was prepared from the corresponding bis-oxazoline derived from (,V)-valine by deprotonation with n-BuLi and transmetallation with allylzinc bromide. This reagent reacted with 78 and afforded the allylated product 136 with high optical purity ( = 99%) (equation 66)101. 

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]. 

A wide variety of silyl ethers can be employed, leading to functionalized homo-allylic alcohols or ethers. This three-component coupling reaction, which generates in a single operation a range of homoallylic ethers, does not require the initial and independent synthesis of the acetal (or ketal) derived from 6. 

A general methodology for the construction of quaternary carbon atoms at the carbonyl carbon of ketones has been successfully exploited for the facile synthesis of ( )-lycoramine (299) (Scheme 30) (165). Thus, the O-allylated o-vanillin 322 was allowed to react with vinyl magnesium bromide followed by Jones oxidation, and the acid-catalyzed addition of benzyl IV-methylcarbamate to the intermediate a,(3-unsaturated ketone furnished 323. Wadsworth-Emmons olefination of 323 with the anion derived from diethyl[(benzylideneami-no)methyl]phosphonate (BAMP) provided the 2-azadiene 324. The subsequent regioselective addition of n-butyllithium to 324 delivered a metalloenamine that suffered alkylation with 2-(2-bromoethyl)-2-methyl-l,3-dioxolane to give, after acid-catalyzed hydrolysis of the imine and ketal moieties, the 8-keto aldehyde 325. Base-catalyzed cycloaldolization and dehydration of 325 then provided the 4,4-disubstituted cyclohexenone 326. The entire sequence of reactions involved in the conversion of 323 to 326 proceeded in very good overall yield and in one pot. 

Asymmetric synthesis of a chroman. Solladie and Moine have effected an en-antiospecific synthesis of the chroman-2-carboxaldehyde 7, a key intermediate in the synthesis of a-tocopherol, from (R)-( +)-l. The phosphonate 2, derived from 1, undergoes a Wittig-Horner reaction with the dimethyl ketal of pyruvaldehyde to afford the optically active vinyl sulfoxide 3. Condensation of the aldehyde 4 with the lithio derivative of 3 affords, after silyl deprotection, the allylic alcohol 5 as the only diastereoisomer. This... 

This strategy has been applied to the synthesis of the Cis Cecropia juvenile hormone (JH) (163 Scheme 13) using the ketal (160) rather than an alkoxy butadiene. Surprisingly, an a,p-unsaturated ester is obtained as an -3 1 mixture from which the undesired ( )-isomer can be separated by fractional distillation. The iterated allylic alcohol (163) is transformed into its isomeric allylic cohol which is subsequently reduced to an alkene and epoxidized to realize the target (163). The scheme also lends itself to... 

Nonsymmetrical coupling reactions have been used extensively by Schafer and coworkers to generate a variety of natural products [1,8-10, 13-17]. A typical procedure calls for the use of a large excess (5-10 equivalents) of one of the acids. In conjunction with a total synthesis of the pheromone brevicomin [8] (21), compounds 24 and 25 (ratio of 5 1) were co-oxidized in methanolic potassium hydroxide to afford ketone 23 in 33% yield. The heterocoupling was complicated by the allylic nature of the radical derived from 24 the undesired coupling isomer constituted 12% of the product. Subsequent treatment of the desired isomer 23 with osmium tetroxide formed diol 22. Acid-catalyzed intramolecular ketalization led to brevicomin (21) in a 42% yield. 

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