Caught in the middle: The ionomycin calcium complex (see structure; O red, Ca green) was the target of an approach featuring the efficient asymmetric synthesis of an allene by a copper(I)-mediated anti-selective S(N)2' reaction, a highly stereoselective gold(III)-catalyzed cycloisomerization of an alpha-hydroxyallene, and a Rh-catalyzed rearrangement of an alpha-diazo-beta-hydroxyketone.

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In this work we study the coordination chemistry of a series of semi-rigid benzotriazole based ligands (L 1-L 3) along with the low coordination number but versatile Ag I ions. This has led to nine new coordination compounds formulated [Ag(L 1)(CF3CO2)] (1), [Ag2(L 1T)2(CF3SO3)2]•2Me2CO (2), [Ag(L 2T)(ClO4)(Me2CO)] (3), [Ag(L 2T)(BF4)(Et2O)] (4), [Ag2(L 3T)2(ClO4)2]2 (5), [Ag(L 3)(NO3)] (6), [Ag2(L 3T)2(CF3CO2)2] (7), [Ag2(L 3T)(CF3SO3)2] (8) and [Ag2(L 3T)2(CF3CF2CO2)2]•2Me2CO (9). These compounds show structural diversity including dimers (5, 7, 9), one dimensional (1D) (3, 4, 6) and two dimensional (2D) (1, 2, 8) coordination polymers. The presence of the two-CH2-units between the three rigid backbones, benzotriazole/-C6H4-/benzotriazole, provides a limited, but significant, flexibility in L 1-L 3 , influencing their variety coordination abilities. Interestingly, certain structures exhibit an isomerism effect (L 1T-L 3T) in the benzotriazole unit when in solid state; a series of studies are indicative of the 1,1-form is generally dominant in solution even in cases where the crystal structure does not contain this tautomer. The homogeneous catalytic efficacy of all compounds against the well-known multi component A 3 coupling reaction and the hydration of alkynes were investigated. Compound 4 was identified as the optimal catalyst for both reactions, promoting the multicomponent coupling as well as the alkyne hydration reaction under low loadings (0.5 and 3 mol%, respectively) and in high yields (up to 99 and 93% in each case).

[reaction: see text]. A novel intermolecular nitrile oxide cycloaddition sequence has been developed for the formation of highly substituted heterocyclic rings. Reaction of trimethylsilyl cyanide with epoxides generates isonitriles which can react with nitroalkenes to form N-(isoxazolylidene)alkylamines. After fragmentation to nitrile oxides, the dipoles can undergo intermolecular 1,3-dipolar cycloadditions with electron deficient dipolarophiles to generate substituted isoxazolines in one synthetic operation.

Ionomycin is a narrow-spectrum ionophore antibiotic isolated from Streptomyces conglobatus. [1] X-ray crystallographic analysis of its calcium complex (1; see Scheme 1) [2] revealed a carboxylic acid group and an unusual b-diketone moiety which, in combination, are responsible for its avidity for divalent cations. Ionomycin has little value as an antibiotic but it is widely used as a tool in cell biology for the investigation of processes requiring calcium mobilization. [3] The three total syntheses reported to date exemplify the utility of chiral enolate chemistry (Evans et al.), [4] the chiron approach (Hanessian et al.), [5] and asymmetric ring-opening of symmetrical 8-oxabicyclo[3.2.1]oct-6-enes (Lautens et al.) [6] for the construction of polypropionate chains. In addition, numerous fragment syntheses have also been reported. [7] Herein, we describe a synthesis of ionomycin and its calcium complex (1) from four key fragments 2-5 (Scheme 1). Our synthesis features: 1) the use of a stereoselective gold(III)catalyzed cycloisomerization of an a-hydroxyallene to create a dihydrofuran ring, and 2) the use of a rhodium-catalyzed rearrangement of an a-diazo-b-hydroxyketone to generate the b-diketone moiety.Our synthesis began with the construction of the C22-C32 bis(tetrahydrofuran) fragment 2. Thus, addition of lithium TMS-acetylide to the known aldehyde 6 [8] gave a racemic propargylic alcohol which was oxidized to the corresponding ketone 7 using pyridinium dichromate (Scheme 2). The asymmetric hydrogen-transfer reaction of ketone 7 by the method of Noyori and Ohkuma [9] led to (R)-9 in 95 % yield and e.r. = 97:3, as determined by 1 H NMR spectroscopic analysis of the mandelate ester. Simultaneous cleavage of the TMS and acetate groups using potassium carbonate in methanol resulted in a water soluble diol (R)-10. This species underwent Sharpless asymmetric epoxidation to form the epoxide intermediate 11, which spontaneously cyclized to the tetrahydrofuran 12. The primary hydroxy group was then removed by tosylation and subsequent reduction using lithium triethylborohydride gave the secondary alcohol 14, which was protected as its TBS silyl ether 15.Addition of the freshly prepared aldehyde 16 to the titanium derivative of alkyne 15 gave the desired propargylic alcohol 17 (anti/syn = 6:1) in accord with the Felkin-Anh model of asymmetric induction (Scheme 3). [10] The corresponding mesylate 18 was treated with MeCu·MgBr 2 ·LiCl by an anti-selective S N 2' mechanism [11] to give allene 19 (d.r. = 6:1) in 93 % yield. Selective removal of the isopropylidene group was accomplished using 0.10 m PPTS in isopropanol at 50 8C to give a mixture of diastereomeric diols (6:1), which were separated by column chromatography. Pure diol 20 was isolated in 53 % overall yield (63 % brsm) for the four steps starting from alkyne 15. In the key step of the sequence, the diol 20 was treated with 1 mol % AuCl 3 in THF at room temperature to afford the dihydrofuran 21 as a single diastereoisomer in 92 % yield. By using the donor solven...