A new concise construction of trans-clerodane diterpenoids is reported in which oxacyclic and trans-hydronaphthalene fragments are coupled, and the critical C9-quaternary carbon stereocenter formed stereoselectively, by 1,6-addition of a tertiary cuprate or a tertiary carbon radical to β-vinylbutenolide. This strategy is specifically illustrated by total syntheses of (-)-solidagolactone (4), (-)-16-hydroxycleroda-3,13-dien-15,16-olide (5, PL3), and (-)-annonene (6).

This tutorial review gives an overview on copper-mediated carbometalation reactions with a special emphasis on carbometalation of cyclopropenes.

The enantioselective synthesis of cyclopropylzinc reagents has been achieved via a copper-catalyzed carbozincation of 3,3-disubstituted cyclopropenes with diorganozinc reagents. The obtained organozinc compounds can be easily functionalized with a broad range of electrophiles, including palladium-catalyzed cross-couplings, affording highly substituted cyclopropanes. The operationally simple procedure using very low quantities of a commercially available and inexpensive copper catalyst provides a new tool for the synthesis of highly enantioenriched cyclopropanes as single diastereoisomers.

Stereoretentive olefin metathesis based on ruthenium dithiolate complexes has become a very active field of research within the past years. This unique catalyst class is able to kinetically produce both Z- and E-alkenes in high stereochemical purity (typically >95:5) starting from stereochemically pure Z- or E-alkenes. The aim of this tutorial review is to organize the reported information concerning ruthenium dithiolate catalysts in a logic manner, thus providing an "operators handbook" for chemists who wish to apply this methodology in synthesis.

The copper-catalyzed conjugate addition of various Grignard reagents to polyconjugated enones (dienone and enynone derivatives) is reported. The catalyst system, composed of copper triflate and an NHC ligand, led to the unusual selective formation of the 1,4-addition products. This reaction allows for the creation of all-carbon chiral quaternary centers with enantiomeric excesses up to 99%. The remaining unsaturation on the 1,4 adducts give access to valuable synthetic transformations.

The highly diastereo- and enantioselective formation of polysubstituted cyclopropanes was easily achieved through the asymmetric copper-catalyzed carbomagnesiation reaction of nonfunctionalized cyclopropene derivatives. The carbometalated species generated in situ readily undergo C-C and C-X bond-forming reactions with various electrophiles with complete retention of configuration.

The evolution of a convergent fragment-coupling strategy for the enantioselective total synthesis of trans-clerodane diterpenoids is described. The key bond construction is accomplished by 1,6-addition of a trans-decalin tertiary radical with 4-vinylfuran-2-one. The tertiary radical is optimally generated from the hemioxalate salt of the corresponding tertiary alcohol upon activation by visible light and an Ir(III) photoredox catalyst. The enantioselective total synthesis of trans-clerodane diterpenoid 1 reported here was accomplished in seven steps from 3-methyl-2-cyclohexenone. The synthetic strategy described in this report allows a number of trans-clerodane diterpenoids to be synthesized in enantioselective fashion by synthetic sequences of 10 steps or less. This study illustrates a powerful tactic in organic synthesis in which a structurally complex target structure is disconnected at a quaternary carbon stereocenter to fragments of comparable complexity, which are united in the synthetic pathway by conjugate addition of a nucleophilic tertiary radical to a fragment harboring an electron-deficient C-C double bond.

The formation of chiral and sterically congested cyclohexanone derivatives has been achieved through a multistep sequence with one single purification step. (n-Butoxymethyl)-diethylamine was identified as a highly efficient reagent for the direct trapping of aluminum enolates. The Lewis acidic character of aluminum suffices to activate the α-aminoether to form in situ an electrophilic iminium species. In return the aluminum enolate is rendered more nucleophilic by coordination of the butoxy group and formation of an aluminate.