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Chiral organophosphorous compounds are very important in catalysis, organic syntheses, and medicinal chemistry. However, catalytic enantioselective protocols for the axially chiral allenyl phosphorus compounds have never been reported. Herein, a palladium-catalyzed enantioselective carbon-phosphorus bond formation reaction affording axially chiral allenyl phosphonates has been developed. The reaction enjoys high yields and ees accommodating a wide range of functional groups. Mechanistic studies have unveiled an overwhelming kinetic resolution process.

In contrast to the widely explored methods for the asymmetric synthesis of molecules bearing a single stereocenter or adjacent stereocenters, the concurrent construction of 1,3-stereogenic centers in an enantio- and diastereoselective manner remains a challenge, especially in acyclic systems. Herein, we report an enantio- and diastereodivergent construction of 1,3-nonadjacent stereocenters bearing allenyl axial and central chirality through synergistic Pd/Cu-catalyzed dynamic kinetic asymmetric allenylation with racemic allenylic esters. The protocol is suitable for a wide range of substrates including the challenging allenylic esters with less sterically bulky substituents and provided chiral allenylic products bearing 1,3-nonadjacent stereocenters with high levels of enantio- and diastereoselectivities (up to >20:1 dr and >99% ee). Furthermore, several representative transformations involving axial-to-central chirality transfer were conducted, affording useful structural motifs containing nonadjacent stereocenters in a diastereodivergent manner.

Enabled by the newly developed ligand, Ming-Phos, the first example of palladium-catalyzed highly enantioselective coupling of racemic propargylic benzoates with organoboronic acids for chiral allenes synthesis has been developed. Excellent asymmetric induction has been achieved with a decent substrate scope. Synthetic potentials for the construction of polycyclic compounds with multiple chiral centers have been demonstrated.

The first palladium-catalyzed asymmetric Heck reaction between aryl triflates and alkynes to give trisubstituted allenes with high er under mild reaction conditions is described. The key to the success is the discovery and fine-tuning of the different N-substituents of Xu-Phos, which ensure the enantioselectivity and reactivity. Synthetic transformation of the chiral allenes with high chirality transfer was also demonstrated.

Three-carbon axial chirality has been asymmetrically established from racemic one-carbon central chirality efficiently at room temperature: we report here the discovery of the first catalytic asymmetric carbonylation of readily available racemic propargylic carbonates to access optically active 2,3-allenoates with fairly high ee. The combination of [(π-allyl)PdCl]2 with [(R)-ECNU-Phos], a new chiral bisphosphine ligand based on a biphenyl skeleton, demonstrates high enantioselectivity. Both enantiomers of allenoates can be obtained at room temperature by applying either (R)- or (S)-ECNU-Phos.

Oxidation from alcohols to carboxylic acids, a class of essential chemicals in daily life, academic laboratories, and industry, is a fundamental reaction, usually using at least a stoichiometric amount of an expensive and toxic oxidant. Here, an efficient and practical sustainable oxidation technology of alcohols to carboxylic acids using pure O2 or even O2 in air as the oxidant has been developed: utilizing a catalytic amount each of Fe(NO3)3·9H2O/TEMPO/MCl, a series of carboxylic acids were obtained from alcohols (also aldehydes) in high yields at room temperature. A 55 g-scale reaction was demonstrated using air. As a synthetic application, the first total synthesis of a naturally occurring allene, i.e., phlomic acid, was accomplished.

Olefins, compounds with a carbon–carbon double bond, are of fundamental importance, and stereodefined construction of tetrasubstituted carbon–carbon double bond is a significant challenge. Here we show a unique and practical method for the preparation of stereodefined, fully substituted olefins via conjugate addition of organozinc reagents to readily available 2,3-allenals. Through mechanistic studies, it is confirmed that the geometry of the newly formed double bond is controlled by unique regiospecific oxygen-protonation of the enolate intermediates, generating 1,3-alkadienols. Such alkadienols would undergo a concerted 1,5-H-transfer reaction via a six-membered transition state to ensure the configuration of the carbon–carbon double bond in the final products. Using the readily available organozinc reagents and 2,3-allenals provides a very rapid access to a wide range of tetrasubstituted olefins with defined stereochemistry, bearing an extremely versatile aldehyde functionality.

We have realized a cyclization reaction of 2,3-allenoic acids 1 in the presence of simple alkyl- or aryl-substituted allenes 3. In this reaction, the cyclic oxypalladation of 2,3-allenoic acid with Pd(II) would afford the furanonyl palladium intermediate 2, which could be trapped by the simple allene to afford a pi-allylic intermediate anti-9. This intermediate anti-9 could be nucleophilically attacked by Br- to yield 4-(1'-bromoalk-2'(Z)-en-2'-yl)furan-2(5H)-one derivatives Z-5 and Pd(0). The in-situ formed Pd(0) was efficiently converted to the catalytically active Pd(II) species by benzoquinone in HOAc. The functional groups, such as malonate, acetoxyl, and phthalic amide in allene 3, are tolerable under the current conditions. High efficiency of chirality transfer was observed when optically active 2,3-allenoic acids were used, which reveals that the formation of the intermediates 2 was a highly stereoselective anti-oxypalladation process. The highly selective formation of Z-isomer may be explained by face-selective coordination of allene 3 with the palladium atom in intermediate 2: the palladium atom coordinates to the terminal C=C double bond of allene 3 from the face opposite to the substituent group to avoid the steric congestion. The products Z-5 could be further elaborated via the S(N)2 nucleophilic substitution with amine or sodium benzenesulfinate, the reduction of the C-Br bond by NaBH(4), and the CuBr.SMe(2)-catalyzed S(N)2'-substitution with CH(3)MgBr.

2-Methylene- or alkylidenecyclopropanyl ketones were easily prepared by the regioselective cyclopropanation of allenes or the reaction of methylene-/alkylidenecyclopropanyllithium with N,N-dimethyl carboxylic acid amides. Due to the presence of the exo-cyclic C=C bond and the strained cyclopropane, their highly selective ring-opening cycloisomerization using PdCl(2)(CH(3)CN)(2), NaI (or PdCl(2)(CH(3)CN)(2) + NaI), and Pd(PPh(3))(4) as catalysts provided five different products, i.e., 4H-pyrans, 2,3,4-trisubstituted furans (or 4,5-disubstituted-3-alkylidene-2,3-dihydrofurans), and 2,3,4,5-tetrasubtituted furans (or 2,4,5-trisubstituted-3-alkylidene-2,3-dihydrofurans) in good yields, respectively, depending on the nature of the catalyst and reaction conditions. The less-substituted C=C bonds in these products can be highly selectively hydrogenated or hydroborated to afford new heterocyclic products stereoselectively. These three types of different reactions may proceed through a highly regioselective cleavage of a carbon-carbon single bond in the cyclopropane ring triggered by regioselective halometalation of the C=C bond and beta-decarbopalladation, halogen anion attack on the nonsubstituted carbon atom of the cyclopropane ring, or the direct oxidative addition of the distal carbon-carbon single bond of the cyclopropane ring with Pd(0). In some cases substituent effects were successfully applied to synthesize 2H-pyrans 8 and 3-alkylidene-2,3-dihydrofurans 5, which also provided some mechanistic information.

A highly regio- and stereoselective halohydroxylation of 1,2-allenyl sulfoxides with X(+) and water was developed. The reaction shows E-stereoselectivity. In the iodohydroxylation reaction, I(2) was used to introduce the iodine atom. For bromohalohydroxylation, CuBr(2), NBS, or Br(2) can be used. When using I(2), NBS, or Br(2), the addition of LiOAc.2H(2)O is necessary for high yields of the halohydroxylation products. The chlorohydroxylation reaction was preformed by milling 1,2-allenyl sulfoxides and CuCl(2).2H(2)O with silica gel. Under the catalysis of a Pd(0) complex, the halohydroxylation products, that is, E-2-halo-1-phenylsulfinyl-1-alken-3-ols, can undergo Sonogashira, Suzuki, and Negishi cross-coupling reactions leading to Z-2-substituted-1-phenylsulfonyl-1-alken-3-ols. The C-S bond of the coupling product may undergo a further coupling reaction with organozincs under the catalysis of an Ni catalyst. Here, the presence of a hydroxyl group is important for a smooth coupling involving the C-S bond. Thus, optically active stereodefined multisubstituted allylic alcohols can be prepared by the reaction of the easily available optically active propargylic alcohols with sulfinyl chloride followed by E-halohydroxylation and a selective Pd- or Ni-coupling reaction.

A Rh(III)-catalyzed o-C–H bond functionalization-based allenylation reaction of allenylsilanes 2 with N-methoxybenzamides 1 affords poly-substituted allenylsilanes with a wide range of attractive functional groups in moderate to excellent yields under very mild conditions (20 °C, compatible with ambient air and moisture). Those products may be transformed to different products with attractive structural features. Careful mechanistic studies suggest the reaction proceeds via o-rhodation, regioselective insertion, and β-H elimination.

An efficient Rh(III)-catalyzed stepwise ortho allylation of N-methoxybenzamides 1 with polysubstituted allenes is reported. This C–H functionalization involving allenes is conducted under very mild conditions (−20 °C or room temperature) and compatible with ambient air and moisture, and it can be applied to terminal or internal allenes with different synthetically attractive functional groups. Highly efficient axial chirality transfer has been realized, yielding optically active lactones.

ZnI(2) has been identified as the catalyst for the one-step synthesis of allenes from terminal alkynes and aldehydes with morpholine as the base in toluene. The reaction is believed to proceed via the intermediacy of propargylic amines, which was converted to allenes by a sequential hydride transfer and beta-elimination process. The reaction is applicable for both aromatic and aliphatic aldehydes. Functionalities such as halide, hydroxyl, or amine may be tolerated.

Cyclometallation of two unsaturated carbon-carbon bonds usually requires the application of low-valent metal catalysts, which could cleave the propargylic ester linkage. Thus, it is desirable to identify a catalyst which could undergo cyclometallation without cleaving the propargylic ester linkage. In this paper, we used trans-RhCl(CO)(PPh(3))(2) to realize the cyclometallation of propargylic 2,3-dienoates. The substituents at the 4-position of allenoate moiety nicely control the reaction pathway: when the 4-position of propargylic 2,3-dienoate 1 was monosubstituted with an aryl group, the bicyclic intermediate 7 formed by the cyclometallation could highly selectively undergo carbometalation with the alkyne moiety in the second molecule of propargylic 2,3-dienoate 1 to afford metallabicyclic intermediates 8a or 8b. Subsequent reductive elimination would afford 9, which could undergo an intramolecular Diels-Alder reaction resulting in the formation of polycyclic bis(delta-lactone)-containing structures 2. The intermediate could be trapped by adding 3-methoxyprop-1-yne affording cyclization-aromatization product 4p highly selectively. If the substituent at the 4-positon of the 2,3-allenoate moiety has a beta-H atom, sequential unimolecular cyclometallation/beta-H elimination/reductive elimination occurs to afford cross-conjugated 5(Z)-alkylidene-4-alkenyl-5,6-dihydropyran-2-ones. The Z-stereochemistry of the exo double bond was determined by the cyclometallation. Some of the alpha,beta-unsaturated delta-lactones could be easily converted to other synthetically useful compounds via reduction reaction, hydrogenation, and iodination/coupling protocol.

An efficient highly regio- and stereoselective iron-catalyzed conjugate addition of 2,3-allenoates with primary or secondary alkyl, phenyl, or vinyl Grignard reagents to synthesize multi-substituted beta,gamma-unsaturated enoates has been reported. The in situ formed magnesium dienolate may readily react with different electrophilic reagents to construct an allylic quaternary carbon at the alpha-position of the ester group.

An efficient protocol for the synthesis of eight-membered bicyclic compounds from the cycloisomerization of 1,2,4Z,7-tetraenes has been established. The possible intermediate for this transformation was trapped by its Diels−Alder reaction with N-ethyl maleimide. Thus the reaction may proceed via the sequential processes involving [1,5]-hydrogen migration and electrocyclization.

Cross-coupling cyclization reaction between 2,3-allenoic acids 1 and 2,3-allenols 2, in which two allenes functioned differently, was realized to afford 4-(1',3'-dien-2'-yl)-2(5H)-furanone derivatives 3. The reaction may proceed via an oxypalladation, insertion, and beta-hydroxide elimination process. A high E-stereoselectivity of the new formed C=C double bond was observed.