The total synthesis of compound 1, a 1,7-dioxaspiro[5.5]undecane derivative of the seco acid methyl ester of erythronolide A, is reported.BRUNO BERNET, PAUL M. BISHOP, MAURICE CARON, TAKESHI KAWAMATA, BERNARD L. ROY, LUC RUEST, GILLES SAUVE, PIERRE SOUCY et PIERRE DESLONGCHAMPS. Can. J. Chem. 63, 2810.La synth2se totale du composC 1, un d6rivC dioxa-1,7 spiro[5.5]undCcane de I'ester mCthylique de I'acide seco de 1'Crythronolide A, est rapportie.We wish to report the stereocontrolled synthesis of the carbamate derivative 2 (Scheme 1) of erythronolide A seco acid methyl ester. Our synthetic strategy, which is based on the fact (3) that stereoelectronic effects control the conformation of the 1,7-dioxaspiro[5.5]undecane system, has been reported elsewhere (4, 5h3The two starting materials used for the construction of the 1,7-dioxaspiro[5.5]undecane derivative 1 were 4-(biscarbomethoxy)-2-methyl-6-valerolactone 3 (Scheme 2) and optically active R-5-hexyn-3-01 (4, R = H). The lactone 34 was prepared from the Michael reaction of dimethyl malonate with methyl methacrylate followed by an aldol condensation with formaldehyde. Optically active R-5-hexyn-3-01 (4, R = H) was obtained by resolution (6) (chromatography of the 0-methyl mandelic esters).Condensation (7) of lactone 3 with the lithium acetylide of optically active 4 (R = (CH3),Si) gave, after treatment with 'NSERCC and FCAC predoctoral fellowships: M. Caron (1979Caron ( -1982, B. L. Roy (1980Roy ( -1984, and G. SauvC (1978SauvC ( -1981; postdoctoral collaborators: B. Bernet (1979Bernet ( -1980, P. M. Bishop (1981Bishop ( -1983, T. Kawamata (1979Kawamata ( -1981; UniversitC de Sherbrooke: "titulaire de recherche" (L. Ruest) et "adjoint de recherche" (P. Soucy).'For total synthesis of erythronolides reported by other groups, see ref. 2. 3Portions of this work have been presented at several international conferences, the first two being the "8th Natural Products Symposium", University of West Indies, Jamaica (January 1980) and the "International Symposium on Stereoelectronic Effects in Organic Chemistry", University of St. Andrews, Scotland (July 1980). 4For all new substances, the spectra (ir, 250-MHz and 60-MHz 'H nmr, and high resolution mass spectra) were in complete agreement with the assigned structures. The I3c nmr spectra were also recorded when necessary for structural assignment.trimethylsilyl chloride, the adduct 5.' Controlled catalytic hydrogenation (5 4 6) followed by cyclization catalyzed with trimethylsilyl triflate (9) gave the optically active spiro diesters 7A and 7B in a -1 : 1 ratio. Equilibration (3) of this C-8 epimeric mixture (erythronolide numbering system) with pyridinium tosylate (10) gave solely the spiroisomer 7B, which has an absolute (and relative) configuration at C-8 and C-13 corresponding to that of 1 derived from erythromycin Allylic oxidation (SeOz, PCC (11)) of isomer 7B provided spiroenone 8 with a carbonyl group at C-12. Lithium dimethylcuprate 1,4-addition (12) on spiroenone 8 and reaction of the resulting enolate with d...

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