Stereoselective Access to Fully Substituted Aldehyde-Derived Silyl Enol Ethers by Iridium-Catalyzed Alkene Isomerization.

An in situ generated cationic Ir-catalyst isomerizes simple allylic silyl ethers into valuable, fully substituted aldehyde-derived silyl enol ethers. Importantly, by judicious choice of substrate, either of the two possible stereoisomers of a given enolate derivative is accessible with complete stereoselectivity. One-pot isomerization-aldol and isomerization-allylation processes illustrate the synthetic utility of this method.

Highly E-Selective, Stereoconvergent Nickel-Catalyzed Suzuki-Miyaura Cross-Coupling of Alkenyl Ethers.

An improved method for the nickel-catalyzed Suzuki-Miyaura cross-coupling of alkenyl ethers is reported. This stereoconvergent protocol allows for the utilization of a wide range of alkenyl ethers and aryl boronic esters for the synthesis of variously substituted styrene derivatives. An olefinic mixture with respect to the alkenyl ethers can be employed, thereby circumventing the stereodefined synthesis of starting materials.

A Tandem Iridium-Catalyzed "Chain-Walking"/Cope Rearrangement Sequence.

An iridium-catalyzed tandem olefin migration/Cope rearrangement of alkenyl ω-ene cyclopropanes is reported. By this means, a variety of complex annulenes are obtained as single diastereomers starting from cyclopropyl ester derived from simple 1,ω-dienes and alkenyldiazo compounds. Long-range olefin migration over up to 10 positions could be realized and coupled with an efficient Cope rearrangement to yield valuable scaffolds.

Diastereo- and enantioselective copper catalyzed hydroallylation of disubstituted cyclopropenes.

A highly diastereo- and enantioselective protocol for the hydroallylation of 1,1- and 1,2-disubstituted cyclopropenes has been developed utilizing an formed copper hydride. A variety of allyl electrophiles could be utilized yielding a diverse range of trisubstituted cyclopropanes. Finally a preliminary enantioselective variant could be established employing a recently described -stereogenic xantphos derivative as ligand.

Walking Metals for Remote Functionalization.

The distant and selective activation of unreactive C-H and C-C bonds remains one of the biggest challenges in organic chemistry. In recent years, the development of remote functionalization has received growing interest as it allows for the activation of rather challenging C-H and C-C bonds distant from the initiation point by means of a "metal-walk". A "metal-walk" or "chain-walk" is defined by an iterative series of consecutive 1,2- or 1,3-hydride shifts of a metal complex along a single hydrocarbon chain.

A Method for the Late-Stage Formation of Ketones, Acyloins, and Aldols from Alkenylstannanes: Application to the Total Synthesis of Paecilonic Acid A.

Treatment of alkenylstannanes with Cu(OAc) /Et N affords the corresponding enol esters or ketones under conditions that proved compatible with many common functionalities; these include groups that would neither survive under the standard Tamao-Fleming conditions for the oxidation of Csp2 -SiR bonds nor under the conditions commonly used to oxidize C-B bonds. Chiral centers adjacent to the unveiled carbonyls are not racemized and competing protodestannation is marginal, even if the substrate carries unprotected -OH groups as internal proton sources. Therefore, the procedure is well suited for the preparation of acyloin and aldol derivatives.

Stereospecific Synthesis of Fluoroalkenes by Silver-Mediated Fluorination of Functionalized Alkenylstannanes.

The known procedures for the conversion of alkenylstannanes into the corresponding fluoroalkenes suffer from largely variable yields and a limited compatibility with functional groups; most notably, protodestannation becomes a serious issue whenever protic sites are present in the substrate. Outlined in this paper is a convenient alternative with a much improved application profile, which is largely unperturbed by free alcohols and amides of all sorts. Key to success is the use of F-TEDA-PF in combination with non-hygroscopic and bench-stable silver phosphinate (AgOP(O)Ph ) that acts as an essentially neutral, non-nucleophilic promotor and effective tin-scavenger at the same time.

Hydroxyl-Assisted Carbonylation of Alkenyltin Derivatives: Development and Application to a Formal Synthesis of Tubelactomicin A.

Alkenyltin derivatives flanked by a hydroxyl group are subject to methoxycarbonylation when treated with catalytic amounts of Pd(OAc)2 and Ph3As in MeOH under a CO atmosphere; key to success is the use of 1,4-benzoquinone as a stoichiometric oxidant in combination with trifluoroacetic acid as a cocatalyst. The acid lowers the LUMO of the quinone and likely marshals the critical assembly of the substrates. Under the optimized conditions, competing proto-destannation is marginal; the method proved compatible with various (acid sensitive) functional groups and was applied to a short formal total synthesis of the antibiotic tubelactomicin A.

Selective Formation of a Trisubstituted Alkene Motif by trans-Hydrostannation/Stille Coupling: Application to the Total Synthesis and Late-Stage Modification of 5,6-Dihydrocineromycin B.

Countless natural products of polyketide origin have an E-configured 2-methyl-but-2-en-1-ol substructure. An unconventional entry into this important motif was developed as part of a concise total synthesis of 5,6-dihydrocineromycin B. The choice of this particular target was inspired by a recent study, which suggested that the cineromycin family of antibiotics might have overlooked lead qualities, although our biodata do not necessarily support this view.