Allylic derivatives natural product synthesis

As a final example of ring-closing allylation in natural product synthesis. Still and co-workers demonstrated that the crotylchromium species derived in situ from the allylbromide 191 undergoes intramolecular allylation to give a 4 1 ratio of adducts 192 and 193, where the major adduct 192 was subsequently converted to asperdiol (Scheme 11-8) [102]. 

An interesting application of the asymmetric alkoxyselenenylation of alkenes to natural product synthesis was reported recently by Wirth, who described a short procedure to obtain some furofuran lignans 147]. The total synthesis of (+)-Samin 53 [47 a] is shown in Scheme 7. The protected allylic alcohol 50 was treated with the selenyl triflate derived from diselenide 29 in the presence of 2,3-butadien-l-ol, and afforded the addition product 51 in 55% yield and with a diastereomeric ratio of 15 1. The favored 5-exo-trig radical cyclization of the major isomer afforded the tetrahydrofuran derivative 52 from which the final product was obtained through few classical steps. 

Alkynic ketones have been used extensively in natural product synthesis, due in large part to the contributions of Midland and coworkers and the development of generd methods for enantioselective reduction of this moiety to afford optically active propargyl alcohols using chiral trialkylboranes. Furthermore, the derived alkynic alcohol is a versatile system which can be manipulated directly into cis-or rra 5-allylic alcohols and as a precursor for vinylorganometallic species. This section will briefly cover progress made in the direct acylation of alkynic organolithiums with the acylation protocol d veloped by Weinreb (see also Section 1.13.2.7). 

The reaction of carbonyl compounds and allylmetal reagents is an important transformation in organic synthesis. Advances in stereoselective carbonyl allylation reactions have been spurred by interest in the synthesis of polypropionate-derived natural products, carbohydrates and other polyhydroxylated compounds. These reactions are ideally suited for the construction of stereochemically rich acyclic skeletons. Additionally, cyclic polyether-containing natural products, among others, have inspired chemists to investigate ring-closing allylation reactions. This review will focus on recent developments in the allylation reaction, with special emphasis on its application towards the synthesis of natural products. 

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. 

Asymmetric cyclopropanation reactions have been developed by using diiodomethane and diethyl zinc in the presence of a chiral Lewis acid. A particularly effective chiral Lewis acid, introduced by Charette, is the dioxaborolane 112, which induces high levels of optical purity in the resultant cyclopropanes derived from allylic alcohols (4.90). This methodology has been used in natural product synthesis, such as in the preparation of the antifungal agent FR-900848 (4.91). ... 

The total synthesis of fluvirucinine A1 127 provides a powerful illustration of the utility of Fu s methodology in natural product synthesis (Scheme 13.34). The asymmetric Negishi reaction of racemic allylic chloride 122 with alkylzinc bromide 123 in the presence of Ni/Pybox catalyst system provided ester 124 in 93% yield and 96% ee. After few steps, the organozinc reagent of bromide 125 was subjected to a second Negishi reaction with chloride 122 under identical coupling conditions to furnish derivative 126 in 80% yield and excellent enantioselectivity. 

One classic application of the Tsuji-Trost reaction in natural products synthesis is found in the synthesis of strychnine by Overman and co-workers in 1993. Reaction of acetoacetate derivative 138 with enantiopure allylic carbonate 137 in the presence of Pd2(dba)3, PPh3, and NaH in THF yielded the cw-adduct 139 in 91%. It is worth noting that the selective displacement of carbonate group occurs with retention of the configuration and proceeds via the reactive 7i-allyl intermediate (see. Scheme 13.38). Derivative 139 could then be elaborated in a number of steps, to complete the total synthesis of strychnine. 

A reiterative application of a two-carbon elongation reaction of a chiral carbonyl compound (Homer-Emmonds reaction), reduction (DIBAL) of the obtained trans unsaturated ester, asymmetric epoxidation (SAE or MCPBA) of the resulting allylic alcohol, and then C-2 regioselective addition of a cuprate (Me2CuLi) to the corresponding chiral epoxy alcohol has been utilized for the construction of the polypropionate-derived chain ]R-CH(Me)CH(OH)CH(Me)-R ], present as a partial structure in important natural products such as polyether, ansamycin, or macro-lide antibiotics [52]. A seminal application of this procedure is offered by Kishi s synthesis of the C19-C26 polyketide-type aliphatic segment of rifamycin S, starting from aldehyde 105 (Scheme 8.29) [53]. 

In two studies toward the total synthesis of natural products it could be shown that the a,jS-unsaturated esters derived from the vinylogous Mukaiyama aldol reactions can be further functionalized into advanced intermediates. The C1-C7 segment of oleandolide commences with the VMAR of aldehyde 68 derived from the Roche ester. The so-generated stereo-triad was protected as PMB ether and the ester 76 was reduced to the allylic alcohol. Sharpless asym-... 

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