γ-Butenolides, γ-butyrolactones, and derivatives, especially in enantiomerically pure form, constitute the structural core of numerous natural products which display an impressive range of biological activities which are important for the development of novel physiological and therapeutic agents. Furthermore, optically active γ-butenolides and γ-butyrolactones serve also as a prominent class of chiral building blocks for the synthesis of diverse biological active compounds and complex molecules. Taking into account the varying biological activity profiles and wide-ranging structural diversity of the optically active γ-butenolide or γ-butyrolactone structure, the development of asymmetric synthetic strategies for assembling such challenging scaffolds has attracted major attention from synthetic chemists in the past decade. This review offers an overview of the different enantioselective synthesis of γ-butenolides and γ-butyrolactones which employ catalytic amounts of metal complexes or organocatalysts, with emphasis focused on the mechanistic issues that account for the observed stereocontrol of the representative reactions, as well as practical applications and synthetic potentials.

S3 General methods:Chromatography: Merck silica gel type 9385 230-400 mesh, TLC: Merck silica gel 60, 0.25 mm. Components were visualized by UV and cerium/molybdenum or potassium permanganate staining. Progress and conversion of the reaction were determined by GC-MS (GC, HP6890: MS HP5973) with an HP1 or HP5 column (Agilent Technologies, Palo Alto, CA). Mass spectra were recorded on an AEI-MS-902 mass spectrometer (EI+) or a LTQ Orbitrap XL (ESI+). 1 H-and 13 C-NMR were recorded on a Varian AMX400 (400 and 100.59 MHz, respectively) using CDCl 3 as solvent. Chemical shift values are reported in ppm with the solvent resonance as the internal standard (CHCl 3 :  7.26 for 1 H,  77.0 for 13 C). Data are reported as follows: chemical shifts, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, br = broad, m = multiplet), coupling constants (Hz), and integration. Carbon assignments are based on APT 13 C-NMR experiments. Melting points were measured using a Büchi Melting Point B-545. All reactions were carried out under a nitrogen atmosphere using oven dried glassware and using standard Schlenk techniques. Dichloromethane was dried and distilled over calcium hydride; THF, Et 2 O and toluene were dried and distilled over sodium. Pd[P( t Bu) 3 ] 2 , was purchased from strem, Pd 2 (dba) 3 , SPhos, XPhos, DavePhos and P( t Bu) 3 were purchased from Aldrich and used without further purification. n BuLi (1.6 M solution in hexane) and PhLi (2.0 M solution in dibutylether) were purchased from Acros. sec BuLi (1.4 M in cyclohexane), MeLi (1.6 M in diethylether), TMSCH 2 Li (1.0 M in pentane), HexLi (2.3 M in hexane), thienylLi (1.0 M in THF/hexane), tert BuLi (1.7 M in pentane) and the compounds used as precursor for the preparation of lithium reagents, namely furan, 1-bromo-2,6-dimethyl-benzene and 1-bromobenzene-3-trifluoromethyl-benzene were purchased from Aldrich. All the bromides were commercially available and were purchased from Aldrich with the exception of 2-bromo-5-phenylthiophene (Maybridge) and 2-(4-bromophenyl)-1,3-dioxolane (Acros). Organolithium other than the aforementioned were prepared according to described procedures (see below).

A simple, high yielding catalytic method for the multigram scale selective epoxidation of electron-rich alkenes using near-stoichiometric H2O2 under ambient conditions is reported. The system consists of a Mn(II) salt (<0.01 mol %), pyridine-2-carboxylic acid (<0.5 mol %), and substoichiometric butanedione. High TON (up to 300 000) and TOF (up to 40 s–1) can be achieved for a wide range of substrates with good to excellent selectivity, remarkable functional group tolerance, and a wide solvent scope. It is shown that the formation of 3-hydroperoxy-3-hydroxybutan-2-one from butanedione, and H2O2 in situ, is central to the activity observed.

Carbon-carbon bond formation is the basis for the biogenesis of nature's essential molecules. Consequently, it lies at the heart of the chemical sciences. Chiral catalysts have been developed for asymmetric C-C bond formation to yield single enantiomers from several organometallic reagents. Remarkably, for extremely reactive organolithium compounds, which are among the most broadly used reagents in chemical synthesis, a general catalytic methodology for enantioselective C-C formation has proven elusive, until now. Here, we report a copper-based chiral catalytic system that allows carbon-carbon bond formation via allylic alkylation with alkyllithium reagents, with extremely high enantioselectivities and able to tolerate several functional groups. We have found that both the solvent used and the structure of the active chiral catalyst are the most critical factors in achieving successful asymmetric catalysis with alkyllithium reagents. The active form of the chiral catalyst has been identified through spectroscopic studies as a diphosphine copper monoalkyl species.

A Cu(I)-phosphoramidite-based catalytic system that allows asymmetric allyl−allyl cross-coupling with high enantioselectivity is reported. This transformation tolerates a large variety of functionalized substrates. The versatility of this new reaction is illustrated in the catalytic asymmetric synthesis of the Martinelline alkaloids chromene derivative core.

Elegant like a butterfly, stings like a lithium reagent: Mono‐ and di‐ortho‐substituted aryllithium reagents were coupled through palladium catalysis with hindered aryl bromides to form highly congested tri‐ and tetra‐ortho‐substituted biaryls. The reaction allows the use of easily accessible ortho‐functionalized aryllithium compounds. The high reactivity of organolithium reagents facilitates a fast process under ambient conditions.

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Copper-catalysis allows the direct oxygen-arylation of dialkyl phosphonates with diaryliodonium salts. This novel methodology proceeds with a wide range of phosphonates and phosphoramidates under mild conditions and gives straightforward access to valuable mixed alkyl aryl phosphonates in very good yields and near perfect selectivity.