One‐Pot Synthesis of Pyrazoles through a Four‐Step Cascade Sequence

A one‐pot synthesis of 3,4,5‐ and 1,3,5‐pyrazoles from tertiary propargylic alcohols and para‐tolylsulfonohydrazide has been accomplished. The pyrazoles are formed through a four‐step cascade sequence, including FeCl₃‐catalyzed propargylic substitution, aza‐Meyer–Schuster rearrangement, base‐mediated 6π electrocyclization, and thermal [1,5] sigmatropic shift. In this reaction, the 3,4,5‐ and 1,3,5‐pyrazoles are produced selectively according to different substituents in the starting alcohols.     

Phosphine‐Free Palladium‐Catalyzed Allene Carbopalladation/Allylic Alkylation Domino Sequence: A New Route to 4‐(α‐Styryl) γ‐Lactams

Free to decide : Various 4‐(α‐styryl) γ‐lactams are synthesized in 61–88 % yield by a phosphine‐free palladium‐catalyzed carbopalladation/allylic alkylation domino sequence (see scheme). The cyclization is totally regio‐ and diastereoselective in favor of the 3,4‐trans‐disubstituted γ‐lactam. The process is successfully applied to the synthesis of a new aza analogue of the naturally occurring lignan (+)‐oxo‐parabenzlactone.

     

Modular Synthesis of Novel Macrocycles Bearing α,β‐Unsaturated Chemotypes through a Series of One‐Pot,Sequential Protocols

A series of one‐pot, sequential protocols was developed for the synthesis of novel macrocycles bearing α,β‐unsaturated chemotypes. The method highlights a phosphate tether‐mediated approach to establish asymmetry, and consecutive one‐pot, sequential processes to access the macrocycles with minimal purification procedures. This library amenable strategy provided diverse macrocycles containing α,β‐unsaturated carbon‐, sulfur‐, or phosphorus‐based warheads.     

Simple Access to Highly Functional Bicyclic γ‐ and δ‐Lactams: Origins of Chirality Transfer to Contiguous Tertiary/Quaternary Stereocenters Assessed by DFT

This paper describes the synthesis of both polysubstituted oxazolo‐pyrrolidinones and ‐piperidinones by a domino process. The methodology is based on the reaction between hydroxyl halogenoamides and Michael acceptors, which leads efficiently to bicyclic lactams. The process is compatible with unsymmetrical electron‐withdrawing groups on the Michael acceptor, which allows the formation of two contiguous and fully controlled tertiary and quaternary stereocenters. In the case of tetrasubstituted Michael acceptors, two adjacent quaternary stereocenters are formed in good yield. Starting from (R)‐phenylglycinol derived amides results in the formation of enantioenriched bicyclic lactams in low to good yields and with high levels of stereoselectivity, thus greatly increasing the scope and interest of this strategy. The origins of chirality transfer and diastereoselectivity were studied by DFT calculations and have been attributed to a kinetic control in one of the last two steps of the reaction sequence. This selectivity is dependent upon both the substituents on the Michael acceptor and the sodium cation chelation.     

One‐Pot Organocatalytic Tandem Aldol/Polycyclization Reactions between 1,3‐Dicarbonyl Compounds and α,β,γ,δ‐Unsaturated Aldehydes for the Straightforward Assembly of Cyclopenta[b]furan‐Type Derivatives: New Insight into the Knoevenagel Reaction

A new cascade pathway viable for Knoevenagel chemistry that involves the coupling between 1,3‐dicarbonyl systems and α,β,γ,δ‐unsaturated aldehydes has been developed. The process comprises the combination of a classic aldol‐type condensation and a rare spontaneous metal‐free cycloisomerization, representing a convergent and innovative approach for the stereoselective synthesis of cyclopenta[b]furan‐type derivatives. The scope and limitations with respect to both reaction partners and mechanistic features were investigated. Meaningfully, our study provides valuable guidance concerning the structural and electronic effects controlling the reactivity of conjugated polyene carbonyl systems.     

Domino Radical Addition/Oxidation Sequence with Photocatalysis: One‐Pot Synthesis of Polysubstituted Furans from α‐Chloro‐Alkyl Ketones and Styrenes

A new domino reaction has been developed that allows the combination of styrenes and α‐alkyl ketone radicals to afford a wide array of polysubstituted furans in good to excellent yields under mild and simple reaction conditions. The key to success of this novel protocol is the use of photocatalyst fac‐Ir(ppy)₃ and oxidant K₂S₂O₈. Mechanistic studies by a radical scavenger and photoluminescence quenching suggest that a radical addition/oxidation pathway is operable.     

One‐Pot Synthesis of N‐Substituted β‐Amino Alcohols from Aldehydes and Isocyanides

A practical two‐stage one‐pot synthesis of N‐substituted β‐amino alcohols using aldehydes and isocyanides as starting materials has been developed. This method features mild reaction conditions, broad scope, and general tolerance of functional groups. Based on a less common central carbon–carbon bond disconnection, this protocol complements traditional approaches that involve amines and various carbon electrophiles (epoxides, α‐halo ketones, β‐halohydrins). Medicinally relevant products can be prepared in a concise and efficient way from simple building blocks, as demonstrated in the synthesis of the antiasthma drug salbutamol. Upgrading the synthesis to an enantioselective variant is also feasible.     

One‐Pot Synthesis of Polysubstituted Benzenes through a N,N‐dimethyl‐4‐aminopyridine (DMAP)‐Catalyzed [4+2] Benzannulation of 1,3‐Bis(sulfonyl)butadienes and γ‐Substituted Allenoates

A new strategy for the one‐pot synthesis of polysubstituted benzenes through a N,N‐dimethyl‐4‐aminopyridine (DMAP)‐catalyzed [4+2] benzannulation from readily prepared 1,3‐bis(sulfonyl)butadienes and γ‐substituted allenoates is described. This method provides a facile, metal‐free and general route to highly substituted benzenes under mild conditions in moderate‐to‐good yields with complete regioselectivity.     

Efficient Domino Hydroformylation/Benzoin Condensation: Highly Selective Synthesis of α‐Hydroxy Ketones

An improved domino hydroformylation/benzoin condensation to give α‐hydroxy ketones has been developed. Easily available olefins are smoothly converted into the corresponding α‐hydroxy ketones in high yields with excellent regioselectivities. Key to success is the use of a specific catalytic system consisting of a rhodium/phosphine complex and the CO₂ adduct of an N‐heterocyclic carbene.     

One‐Pot Synthesis of Lactams from Cycloalkanes and tert‐Butyl Nitrite by Using N‐Hydroxyphthalimide as Key Catalyst

Lactams were successfully synthesized in the one‐pot reaction of cycloalkanes and tBuONO in the presence of N‐hydroxyphthalimide as a key catalyst. Cyclododecane and cyclohexane were treated with tBuONO followed by triethylamine and then cyanuric chloride in a one‐pot manner to give laurolactam and ε‐caprolactam, respectively, in good yields. The Beckmann rearrangement of oximes by cyanuric chloride was found to be accelerated by the use of 1,1,1,3,3,3‐hexafluoro‐2‐propanol as solvent. The method provides the first successful environmentally benign direct synthetic route to lactams from cycloalkanes without the formation of any salt.     

Palladium‐Catalyzed Oxidative Carbonylation of N‐Allylamines for the Synthesis of β‐Lactams

β‐Lactam scaffolds are considered to be ideal building blocks for the synthesis of nitrogen‐containing compounds. A new palladium‐catalyzed oxidative carbonylation of N‐allylamines for the synthesis of α‐methylene‐β‐lactams is reported. DFT calculations suggest that the formation of β‐lactams via a four‐membered‐ring transition state is favorable.     

One‐Pot Organocatalytic Asymmetric Synthesis of 3‐Nitro‐1,2‐dihydroquinolines by a Dual‐Activation Protocol

Generally, amine‐catalyzed enantioselective transformations rely on chiral enamine or unsaturated iminium intermediates. Herein, we report a protocol involving dual activation by an aromatic iminium and hydrogen‐bonding. An enantioselective aza‐Michael–Henry domino reaction of 2‐aminobenzaldehydes with nitroolefins has been developed through this protocol using primary amine thiourea catalysts to provide a variety of 3‐nitro‐1,2‐dihydroquinolines in moderate yields and with up to 90 % ee. The mechanism for the catalytic enantioselective reaction was confirmed by ESI mass spectrometric detection of the reaction intermediates. The products formed are substructures found in skeletons of important biological and pharmaceutical molecules.     

One‐Pot Sequential Organocatalysis: Highly Stereoselective Synthesis of Trisubstituted Cyclohexanols

A highly diastereoselective (d.r. >99:1) and enantioselective (ee value up to 96 %) synthesis of trisubstituted cyclohexanols was achieved by using a one‐pot sequential organocatalysis that involved a quinidine thiourea‐catalyzed tandem Henry–Michael reaction between nitromethane and 7‐oxo‐hept‐5‐en‐1‐als followed by a tetramethyl guanidine (TMG)‐catalyzed tandem retro‐Henry–Henry reaction on the reaction products of the tandem Henry–Michael reaction. Through a mechanistic study, it has also been demonstrated that similar results may also be achieved with this one‐pot sequential organocatalysis by using the racemic Henry product as the substrate.