[formula: see text] Addition of a very modest amount of lead tetraacetate (1.50 equiv relative to the amount of Grubbs catalyst) to ring-closing metathesis reaction mixtures effectively removes all colored ruthenium and phosphine impurities to deliver colories reaction products.

Muconin (1) is a novel tetrahydropyran-bearing acetogenin isolated from Rollinia mucosa that has exhibited potent and selective in vitro cytotoxicities against pancreatic and breast tumor cell lines. 1 We considered the possibility of preparing 1 by the convergent assembly of readily accessible chiral units (Scheme 1). We describe herein the total synthesis of muconinsthe first of any THP-bearing Annonaceous acetogenin 2 sby taking advantage of such a chiral building block approach.Our laboratories uncovered recently a highly effective method for the hydrolytic kinetic resolution (HKR) of terminal epoxides catalyzed by cobalt complex 8 (eq 1). 3 The HKR provides practical access to both terminal epoxides and 1,2-diols in highly enantioenriched form. The commercial availability on a bulk scale of racemic terminal epoxides such as tetradecene oxide, epichlorohydrin, and propylene oxide render these attractive starting materials for the synthesis of muconin. The fourth requisite building block, dihydropyran 5, is also readily accessed in enantioenriched form using the recently discovered hetero-Diels-Alder condensation of 1-methoxy-3-[(trimethylsilyl)oxy]-1,3-butadiene with aldehydes catalyzed by chromium complex 9 (eq 2). 4 To synthesize fragment 2, the HKR of (()-tetradecene oxide using 0.5 mol % of complex (S,S)-8 in TBME and 0.5 equiv of H 2 O afforded (R)-tetradecane-1,2-diol 4 in >99% ee and in 90% of the theoretical yield. 5 Selective protection of the secondary hydroxyl group was effected by the method of Yamamoto using trimethyl orthoformate and DIBALH. 6 The resulting primary alcohol 10 was transformed to the corresponding aldehyde without detectable epimerization by means of TEMPO-catalyzed oxidation with hypochlorite. 7 Chelation-controlled addition of vinylmagnesium bromide in CH 2 Cl 2 with MgBr 2 ‚OEt 2 8 at -78°C provided the desired allylic alcohol in 74% yield and >100:1 diastereoselectivity. This material was converted to acid 11 in 92% yield by alkylation with sodium iodoacetate in THF.Pyranol 12 was constructed by the hetero-Diels-Alder condensation of 1-methoxy-3-[(trimethylsilyl)oxy]-1,3-butadiene with p-bromobenzyloxyacetaldehyde catalyzed by 2 mol % (S,S)-9 followed by diastereoselective Luche reduction. 9 The moderate enantioselectivity of the catalytic reaction (80% ee) was reconciled by recrystallization of the dihydropyranone condensation product to 99% ee and in good yield. Esterification of 12 with acid 11 was effected cleanly under EDC coupling conditions. The corresponding silyl ketene acetal was generated with LDA in 4:1 THF/ HMPA and in situ trapping with TMSCl. 10 Ireland-Claisen rearrangement 11 occurred upon elevation of the reaction temperature to 50°C, with formation of the 2,6-cis-disubstituted dihydropyran isolated as the methyl ester in 81% yield and 5:1 diastereoselectivity at C(18). The observed preferential formation of the threo stereoisomer is attributable to sigmatropic rearrangement of the Z-silyl ketene acetal through a boatlike transition state. 12 The methyl...

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The exo,exo-bis(isodicyclopentadienyl)magnesium sandwich and the monomeric exo-(isodicyclopentadienyl)butylmagnesium TMEDA complex have been synthesized and characterized by 1H and 13C NMR spectroscopy in C6D6 solution. The solid-state structures were determined by X-ray crystallography. The stereoselectivity with which both moisture-sensitive compounds react with TiCl3·3THF and ZrCl4 was assessed and suitably compared to related observations recorded for alkali metal (Li+, Na+, and K+) complexes of isodicyclopentadiene.