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An expedient method for the C-methylation of alkenylstannanes with formation of trisubstituted alkenes is described, which relies on the use of MeI in combination with copper thiophene-2-carboxylate (CuTC) as promotor and tetra-n-butylammonium diphenylphosphinate as an effective tin scavenger; in some cases, it proved beneficial to further supplement the mixture with catalytic amounts of Pd(PPh 3 ) 4 . Under these conditions, the reaction is robust, high yielding, and compatible with many functional groups that might not subsist under more traditional conditions used to C-alkylate organotin derivatives. A qualitative analysis of the reaction profile suggested that the in situ formation of a reactive organocopper intermediate and its interception by MeI is only barely faster than O-methylation of the phosphinate additive by the same alkylating agent. To guarantee high yields and prevent net protodestannation from occurring, the reaction protocol had to be optimized such that these competing processes are properly decoupled. The new method is particularly well suited for the stereoselective preparation of the (E)-2-methylbut-2-en-1-ol motif that is present in numerous natural products. Alternatively, this particular target structure can be accessed starting from α-hydroxy alkenylsiloxane precursors, which get C-methylated upon exposure to CuI/LiOtBu and MeI by what is thought to be a Brook rearrangement/ alkylation sequence. The required substrates are best prepared by ruthenium-catalyzed trans-hydrosilylation or trans-hydrostannation of propargyl alcohols., (© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Conflicting reports are found in the literature on whether the ortho-pyrrolophane derivative 6, which has been named "butylcycloheptylprodigiosin" even though it is a cyclononane derivative, is a natural product or merely a mis-assigned structure. This dispute has now been resolved by an unambiguous total synthesis of this complex alkaloid which confirms the initial structure assignment. The chosen approach is largely catalysis-based, featuring the first application of a "Narasaka-Heck" reaction in natural product chemistry. This palladium-catalyzed transformation allows the unsaturated oxime ester 26 to be converted into the bicyclic dihydropyrrole 27. Other notable reactions of the reported approach to 6 are a regioselective Tsuji-Trost reaction of the doubly allylic acetate 21 with methyl acetoacetate, a base-induced aromatization of 27 to the corresponding pyrrole 28, a chemoselective oxidation of the benzylic methyl group in 33 with cerium ammonium nitrate in a biphasic reaction medium that does not affect the labile pyrrole nucleus, and a Suzuki cross-coupling for the completion of the heterocyclic domain. Diversification in the latter step leads to a set of analogues that differ from the natural product in the terminal (hetero)arene ring. This structural modification results in complete loss of the very pronounced ability of the parent compound 6 to induce oxidative cleavage in double stranded DNA in the presence of Cu(II). Several cyclononane-, cyclononene- and cyclononadiene derivatives prepared en route to 6 have been characterized by crystal structure analysis, allowing the conformational behavior of nine-membered carbocycles to be studied.

A convergent total synthesis of the antibiotic macrolide myxovirescin A1 (1) is described that is largely based on reagent- and catalyst-controlled transformations. This includes a highly regioselective Negishi reaction of dibromo-alkene 48 with an alkynylzinc reagent, and a palladium catalyzed alkyl-Suzuki coupling of the resulting enyne derivative 12 with the 9-BBN-adduct derived from alkene 61. The latter was obtained via an asymmetric hydrogenation of the chlorinated beta-ketoester 49 and an anti-selective oxyallylation of the functionalized aldehyde 53 as the key steps. The preparation of the bis-borylated allyl-donor 57 used in the oxyallylation step, however, required careful optimization and led to important insights into the nature of the classical hydroborating agent "di(isopinocampheyl)borane (Ipc2BH)". It was unambiguously shown by X-ray crystallography that in the solid state this compound is dimeric, but it is prone to undergo an essentially quantitative mono-deborylation when dissolved in CH2Cl2 or benzene; its composition in ethereal solvents is even more complex as evident from 11B NMR data. Product 71 derived from 12 and 61 was elaborated into the enyne-yne derivative 75, which served as the substrate for an exquisitely selective ring closing alkyne metathesis reaction (RCAM) catalyzed by the molybdenum tris-amido complex 20 activated in situ with CH2Cl2. The resulting cyclic enyne 76 was subjected to a ruthenium catalyzed trans-hydrosilylation/proto-desilylation tandem. Although [Cp*Ru(MeCN)3]PF6 had previously been recommended as catalyst of choice for trans-hydrosilylation reactions of internal alkynes, this complex failed to afford the desired product, whereas its sterically less hindered congener [CpRu(MeCN)3]PF6 permitted the reaction to be performed in appreciable yield, but at the expense of a lower stereoselectivity. AgF-mediated proto-desilylation of the isomeric silanes 79 and 80 followed by cleavage of the remaining acetal protecting groups afforded myxovirescin A1 and its hitherto unknown 14Z-isomer 81, respectively.