Natural product synthesis allyl acetate

A concentrated solution of LiCl04 in EtzO is effective in the allylation of silyl enolates with allyl alcohols and acetates.310 The LiClCL-promoted reaction with silyl enolates enables ring opening of 8-oxabicyclo[3.2.1]octa-2,6-dienes to highly functionalized 1,4-cycloheptadienes, which can be further manipulated for use in natural product synthesis (Equation (83)).311... 

A final example of the use of tartrate-derived crotylboronates in natural product synthesis is illustrated in the formal total synthesis of ikarugamicin (Scheme II-11) [179]. Here, Roush and Wada used the asymmetric crotylboration of meso-(t/" -2,4-hexadien-1,6-dial)iron tricarbonyl 266 with (S,S)-(E)-219 to set three stereocenters in their synthesis of the a,s-indacene unit of ikarugamycin. This key reaction provided 267 in 90% yield and >98% ee. Homoallylic alcohol 267 was converted to the allylic acetate 268, which underwent stereoselective ethylation with EtsAl with retention of stereochemistry. The resulting adduct 269 was subsequently elaborated to as -indacene unit 271 through a 15-step synthetic sequence, including the intramolecular Diels-Alder reaction of 270. 

Kozikowski, A.P., and Sorgi, K.L., Use of the anomeric allylation reaction in natural products synthesis. A stereocontrolled synthesis of methyl deoxypseudomonate B, Tetrahedron Lett., 25, 2085, 1984. Hammond, G.B., Cox, M.B., and Wiemer, D.F., Stereocontrol in Homer-Wadsworth-Emmons condensations of a gezw-dimethylcyclopropyl aldehyde with a-substituted phosphono acetates, J. Org. Chem., 55, 128, 1990. 

The stereoselective total synthesis of (+)-epiquinamide 301 has been achieved starting from the amino acid L-allysine ethylene acetal, which was converted into piperidine 298 by standard protocols. Allylation of 297 via an. V-acyliminium ion gave 298, which underwent RCM to provide 299 and the quinolizidine 300, with the wrong stereochemistry at the C-l stereocenter. This was corrected by mesylation of the alcohol, followed by Sn2 reaction with sodium azide to give 301, which, upon saponification of the methyl ester and decarboxylation through the Barton procedure followed by reduction and N-acylation, gave the desired natural product (Scheme 66) <20050L4005>. 

In another variant of such reactions, the hemi-acetal 104, generated in situ by reaction of the corresponding allylic alcohol with acetaldehyde, undergoes cyclization in the presence of HgClOAc to afford the mercurated acetal 105.128 Under these conditions, the reaction leads to the jy -product with a high selectivity (dr > 10 1 Scheme 14). The same strategy has been applied iteratively for the stereoselective synthesis of natural products containing 1,3,5,7,9-pentaether chains.129... 

Among the most commonly applied chiral moiety for nitrones (2) is the N-a-methylbenzyl substituent (Scheme 12.6) (18-25). The nitrones 8 with this substituent are available from 1 -phenethylamine, and the substituent has the advantage that it can be removed from the resulting isoxazolidine products 9 by hydrogeno-lysis. This type of 1,3-dipole has been applied in numerous 1,3-dipolar cycloadditions with alkenes such as styrenes (21,23), allyl alcohol (24), vinyl acetate (20), crotonates (22,25), and in a recent report with ketene acetals (26) for the synthesis of natural products. Reviewing these reactions shows that the a-methylbenzyl group... 

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 monoallylation of tetronic acid can be achieved by using it in large excess with respect to the allyl acetate (30). Node and co-workers used this method to prepare 31 as a step in the synthesis of the natural product 32 (94T8337), as shown in Scheme 8. 

Zacchino, S.A. and Badano, H. (1991) Enantioselective synthesis and absolute configuration assignment of erythro-(3,4-methylenedioxy-7-hydroxy-1 -allyl-3, 5 -dimethoxy)-8-0-4 -neolignan and its acetate, isolated from nutmeg (Myristica fragrans). Journal of Natural Products 54(1), 155-1 60. 

A recent example of an intermolecular [3 + 4] cycloaddition starts with an allylic acetal, as shown in Eq. (167) [419,420]. Other Lewis acids, for example AlEt Cl3 (n = 0-3), TMSOTf, TfOH, SbCL, SnCL were less effective. Although the exact nature of the transition state is still uncertain, the stereochemistry of the product might be explained on the basis of the rule of endo addition with the least hindered approach of the diene. The possibility of asymmetric synthesis starting with the same substrate with a chiral acetal moiety has been mentioned (see Table 15). 

Tt-Allylnickel halides. Billington has reviewed the preparation of these complexes from allylic halides using Ni(CO)4 or Ni(COD)2, and their use in synthesis, mainly of natural products (54 references). These complexes react with a wide range of both aliphatic and aryl bromides or iodides as well as aldehydes, ketones, epoxides, and quinones. One advantage is that both allyl ligands react. They do not react with acid chlorides, esters, ethers, nitriles, or acetals. 

The unusual 6-azabicyclo[3.2.1]oct-3-ene core of the alkaloid (+)-peduncularine was assembled using the [3+2] annulation of an allylic silane with chlorosulfonyl isocyanate by K.A. Woerpel and co-workers. In the endgame of the total synthesis, the bicyclic aldehyde was masked as the acetal, and an efficient Fischer indole synthesis was performed using phenylhydrazine hydrochloride along with 4% H2SO4. Several subsequent steps led to the natural product. 

The synthesis of the bioactive natural product warburganal from (-)-sclareol was carried out by A.F. Barrero et al. The bicyclic allylic acetate was epoxidized and deacetylated under basic conditions. Next, the solution of the ketoepoxide in glacial acetic acid was treated with hydrazine hydrate and the resulting mixture was heated at reflux for 30 minutes to afford the bicyclic allylic did in excellent yield. 

Compared with the previous coupling types, much less has been reported with these relatively more difficnlt conplings. Exceptionally, conplings with allyl electrophiles, usually allyl acetates or halides, have been often nsed in the synthesis of complex natural products.A noteworthy example is the synthesis of the azaspiracids 1-3 (115a-c), neurotoxins isolated from mussels, whose structure was determined by total synthesis by Nicolaon and coworkers.This synthesis features a notable Stille... 

Panek et al. introduced the synthesis of optically active crotylsilanes by Claisen rearrangement of allyl vinyl ethers derived from homochiral y-silylated allyl alcohols (Scheme 10.141) [393]. These allylsilanes have been used for highly diastereo-and enantioselective allylation of aldehydes and acetals [334], which enables efficient syntheses of complex natural products [394]. 

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