Cristina Aragoncillo

Additions of Allenyl/Propargyl Organometallic Reagents to 4‐Oxoazetidine‐2‐carbaldehydes: Novel Palladium‐Catalyzed Domino Reactions in Allenynes

Metal-mediated carbonyl allenylation and propargylation of 4-oxoazetidine-2-carbaldehydes were investigated in aqueous environment. Different propargyl bromide and metal promoters showed varied regio- and stereoselectivities on product formation. In addition, an unprecedented one-pot stereoselective synthesis of beta-chlorinated allylic alcohols, which can also be considered as functionalized allylsilanes, has been developed, which involves tin(IV) chloride-mediated reaction of propargyltrimethylsilane and 4-oxoazetidine-2-carbaldehydes. Some of the resulting coupling products were submitted to transition metal catalyzed reactions, such as the allenic Pauson-Khand and palladium-catalyzed reactions, leading to novel fused or bridged tricyclic beta-lactams. Remarkably, a novel domino process, namely the allene cyclization/intramolecular Heck reaction was found. A likely mechanism for the cascade reaction should involve an intramolecular cyclization on a (pi-allyl)palladium complex and a Heck-type reaction.

Cyclization reactions of bis(allenes) for the synthesis of polycarbo(hetero)cycles

The chemistry of allenes is an appealing topic which fascinates chemists nowadays. Their reactivity and versatility makes this skeleton a useful moiety to create a great variety of structures depending on the functional groups attached and the reaction conditions used. Recently, there is a growing interest in the study of the reactivity of bis(allenes) inspired in the chemistry developed in simple allenes. In this review a collection of examples of cyclization reactions of bis(allenes) is presented as well as the future perspectives.

A Novel One‐Step Approach for the Preparation of α‐Amino Acids, α‐Amino Amides, and Dipeptides from Azetidine‐2,3‐diones

A remarkable reaction of azetidine-2,3-diones with primary as well as secondary amines, and water is presented. Simply by varying the nucleophile, an unprecedented one-step synthesis of α-amino acids, α-amino amides, and dipeptides, was developed in both the racemic and optically pure forms. The current mechanistic hypothesis invokes a concerted process involving CO extrusion. However, a stepwise pathway can also account for these novel transformations.

Asymmetric synthesis of densely functionalized 3-substituted 3-hydroxy-β-lactams via novel, highly stereoselective Baylis-Hillman and allylation reactions of enantiopure 3-oxo-2-azetidinones

Abstract New asymmetric routes based on both Baylis-Hillman and allylation reactionsof enantiopure 3-oxo-2-azetidinones are used for the highly stereoselective, efficient preparation of densely functionalized 3-substituted 3-hydroxy-β-lactams.

Organocatalyzed three-component Ugi and Passerini reactions of 4-oxoazetidine-2-carbaldehydes and azetidine-2,3-diones. Application to the synthesis of γ-lactams and γ-lactones.

The organocatalyzed U-3CR of 4-oxoazetidine-2-carbaldehydes has been studied. In addition, the organocatalyzed P-3CR of 4-oxoazetidine-2-carbaldehydes and azetidine-2,3-diones has been described for the first time. U-3CR and P-3CR adducts have been obtained in good yields and reasonable diastereoselectivities. Phenyl phosphinic acid has been the catalyst of choice to study the scope of both organocatalyzed multicomponent reactions using a variety of β-lactams, isocyanides, and amines. Highly functionalized U-3CR and P-3CR adducts derived from β-lactams have proved to be useful substrates for the preparation of enantiopure γ-lactams and γ-lactones via N1-C2 β-lactam ring opening/cyclization under acidic or basic conditions.

Regio- and diastereoselective synthesis of β-lactam-triazole hybrids via Passerini/CuAAC sequence.

Passerini (P-3CR) and Passerini-Smiles reactions were investigated in azetidine-2,3-diones, affording the corresponding 3,3-disubstituted-β-lactams with complete diastereoselectivity in high yields. The study has been carried out using different isocyanides, carboxylic acids, and phenols showing the scope of both reactions. In addition, the regioselective synthesis of highly functionalized β-lactam-triazole hybrids has been developed via a Passerini/CuAAC sequence. Interestingly, the use of dialkynes/diazides or trialkynes/triazides as linkers in the CuAAC step has allowed the synthesis of C(2) and C(3) symmetric β-lactam-triazole hybrids, respectively.

Rhodium-Catalyzed Synthesis of 3-Hydroxy-β-lactams via Oxonium Ylide Generation: Three-Component Reaction between Azetidine-2,3-diones, Ethyl Diazoacetate, and Alcohols

3-Substituted-3-hydroxy-beta-lactams, with two new adjacent stereogenic centers, have been prepared in a single step by a rhodium-catalyzed, three-component reaction between azetidine-2,3-diones, ethyl diazoacetate, and alcohols. Good to moderate stereoselectivity was obtained depending on the alcohol used. The stereochemistry of the new centers has been undoubtedly assigned by single crystal X-ray diffraction.

Microwave-promoted synthesis of bicyclic azocine-β-lactams from Bis(allenes)

A metal-free preparation of structurally novel bicyclic azocine-β-lactams has been developed. The first examples accounting for the preparation of eight-membered rings from bis(allenes) in the absence of metals have been achieved by the thermolysis of nonconjugated 2-azetidinone-tethered bis(allenes) on application of microwave irradiation. This selective carbocyclization reaction has been studied experimentally, and additionally, its mechanism has been investigated by a DFT study.

Tunable Metal-Catalyzed Heterocyclization Reactions of Allenic Amino Alcohols: An Experimental and Theoretical Study

Controlled preparation of 2,5-dihydro-1H-pyrroles, 3,6-dihydro-2H-pyrans, and pyrroles has been achieved through switchable chemo- and regioselectivity in the metal-catalyzed heterocyclization reactions of allenic amino alcohols. The gold-catalyzed cycloisomerization reaction of α-amino-β-hydroxyallenes was effective as 5-endo cyclization by addition of amino functionality to the distal allene carbon to yield enantiopure 2,5-dihydro-1H-pyrroles, whereas their palladium-catalyzed cyclizative coupling reactions furnished 3,6-dihydro-2H-pyrans through a chemo- and regioselective 6-endo cycloetherification. Conversely, the gold-catalyzed heterocyclization reaction of β-amino-γ-hydroxyallenes generated exclusively pyrrole derivatives. These results could be explained through a chemo- and regioselective 5-exo aminocyclization to the central allene carbon followed by aromatization. Chemo- and regioselectivity depend on both linker elongation as well as the type of catalyst. This behavior can be justified by means of density functional theory calculations.

Metal‐Free Allene‐Based Synthesis of Enantiopure Fused Polycyclic Sultones

The controlled metal-free preparation of fused δ-sultone derivatives has been developed starting from hydroxyallenynes. The use of 2-(3,3-diethyltriaz-1-enyl)-4-methylbenzene-1-sulfonyl chloride in a sulfonylation/rearrangement sequence gives access to 1,3-dien-2-yl arenesulfonates. These functionalized enynes suffered a direct cyclization/desaturation radical cascade, allowing the synthesis of a variety of enynyl [1,2]oxathiine 1,1-dioxides. Stereoselective cyclization of the readily formed core through intramolecular Diels-Alder reaction has also been demonstrated, affording β-lactam- and glucofuranoside-fused δ-sultone polycycles. These selective reactions have been studied experimentally and additionally, their reaction mechanisms have been investigated computationally by means of density functional theory calculations.