Diazo Decomposition Research Articles

Diazo Decomposition and Carbene Transfer Mediated by a Pincer Gold(III) Complex

Diazo Decomposition and Carbene Transfer Mediated by a Pincer Gold(III) Complex

Pd‐Catalyzed [3+6+3+6] Macrocyclizations of Aryl α‐Diazo‐β‐Ketoesters

AbstractThanks to Pd(II)‐catalysis, an efficient synthesis of unsaturated macrocycles is achieved by [3+6+3+6] condensation of cyclic ethers with aryl α‐diazo‐β‐ketoesters. The presence of the electron‐rich aryl ester moieties forbids the use of dirhodium complexes as these diazo decomposition catalysts provoke unforeseen intermolecular Csp2−H insertion reactions that derail the targeted reactivity. However, with Pd(acac)2, using high concentration conditions (1 M), a variety of 18‐membered macrocycles (16 examples) is afforded with both aryl and alkyl diazo reagents. Catalyst selection for either electrophilic aromatic substitution (Rh) or ylide (Pd) pathways are explained by computational approaches.

Rhodium(I)-Catalyzed O-H Insertions on O-Protected α-Diazo-β-Hydroxyesters.

The X-H insertion reaction constitutes a powerful tool to create diversity through the diazo decomposition of diazocarbonyl compounds. However, until now, X-H insertion on α-diazo-β-aryl-β-hydroxyester scaffolds, readily prepared by aldol-type addition, remained a challenge for the organic chemist. We report herein the first O-H insertions on O-protected α-diazo-β-aryl-β-hydroxyesters, providing straightforward access to a wide range of α,β-dioxygenated esters through modulation of the alcohol and of the aryl substituent. The key feature to achieving this transformation is the use of Rh(I) catalysts, which proved to be crucial to favor the targeted O-H insertion product over the competing 1,2-H and 1,2-Ar migration products. Overall, 32 O-H insertion products have been prepared, in moderate to good yields, with a diastereoisomeric ratio up to 7.5:1 in favor of the syn diastereoisomer.

Construction of Ge-Stereogenic Center by Desymmetric Carbene Insertion of Dihydrogermanes.

We developed a method for the enantioselective synthesis of germanium-stereogenic compounds by the desymmetric carbene insertion of dihydrogermanes. A chiral rhodium phosphate catalyst decomposes diaryldiazo-methanes to generate rhodium carbenes that insert enantioselectively into one of the two Ge-H bonds of dihydrogermanes to form germanium-stereogenic compounds under mild reaction conditions. By this method, a variety of chiral germanes with germanium-stereogenic centers were synthesized in high yields and excellent enantioselectivities. Kinetic studies of the reaction showed that the diazo decomposition process was the rate-determining step. The remaining Ge-H bond of the chiral germane products provides a possibility for preparing chiral tetra-substituted germanium-stereogenic compounds.

Heteroleptic Dirhodium(II) Complexes with Redox‐Active Ferrocenyl Ligands: Synthesis, Electrochemical Properties, and Redox‐Responsive Chemoselectivity in Carbene C−H Insertion

AbstractA series of original heteroleptic dirhodium(II) complexes (4 a–j) of formula [Rh2(OAc)3(L)], where L is a redox‐active ferrocenecarboxylate ligand, has been prepared. These dirhodium(II) complexes have been characterised by NMR, mass spectrometry and cyclic voltammetry. All complexes show a quasi‐reversible redox behaviour for the ferrocenyl unit. The latter can be selectively oxidised by [N(4‐C6H4Br)3]+BF4−. Four selected heteroleptic complexes 4 a, 4 b, 4 f and 4 i, have been evaluated as catalysts for the intramolecular decomposition of a diazo compound 5. The ratio between the aromatic substitution product 6 and the aliphatic C−H insertion product 7 increases (up to 19 % increase) when using the in situ generated oxidised form of the dirhodium(II) complexes (4 a+BF4− to 4 i+BF4−). This shows that the oxidation of the ferrocenecarboxylate ligand has an effect on the chemoselectivity of the dirhodium‐catalysed diazo decomposition, and thus that the electronic properties of a complex can be tuned without exchanging ligands.

Spirocyclic Amide Acetal Synthesis by [CpRu]‐Catalyzed Condensations of α‐Diazo‐β‐Ketoesters with γ‐Lactams

AbstractThe synthesis of spirocyclic amide acetals (33–93 %) has been achieved through Ru(II)‐catalyzed condensations ofN‐carbamate protected pyrrolidinones with metal carbenes derived from α‐diazo‐β‐ketoesters. Thanks to the mildness of the diazo decomposition conditions induced by a 1 : 1 combination of [CpRu(MeCN)3][BArF] and 1,10‐phenanthroline, the formation of the sensitive products is possible. Full characterization of this carbonyl‐ylide mediated process is provided by DFT calculations.

External Photocatalyst-Free Visible Light-Promoted 1,3-Addition of Perfluoroalkyl Iodides to Vinyldiazoacetates

External Photocatalyst-Free Visible Light-Promoted 1,3-Addition of Perfluoroalkyl Iodides to Vinyldiazoacetates

Recent advances in [3+2] cycloaddition of allenes with 1,3-carbonyl ylides; Rh(ii)-catalyzed access to bridged polyoxocarbocyles

This study summarizes the stereochemical outcomes of [3+2] cycloaddition of allene molecules with 1,3-dipolar carbonyl ylides derived from Rh(ii) carbene-mediated diazo decomposition for the formation of highly diastereoselective poly oxacarbocycles.

Preparation and Structural Characterization of [CpRu(1,10‐phenanthroline)(CH3CN)][X] and Precursor Complexes (X=PF6, BArF, TRISPHAT‐N)

AbstractCationic [Ru(η5‐C5H5)(CH3CN)3]+ complex, tris(acetonitrile)(cyclopentadienyl)ruthenium(II), gives rise to a very rich organometallic chemistry. Combined with diimine ligands, and 1,10‐phenanthroline in particular, this system efficiently catalyzes diazo decomposition processes to generate metal‐carbenes which undergo a series of original transformations in the presence of Lewis basic substrates. Herein, syntheses and characterizations of [CpRu(Phen)(L)] complexes with (large) lipophilic non‐coordinating (PF6− and BArF−) and coordinating TRISPHAT‐N− anions are reported. Complex [CpRu(η6‐naphthalene)][BArF] ([1][BArF]) is readily accessible, in high yield, by direct counterion exchange between [1][PF6] and sodium tetrakis[3,5‐bis(trifluoromethyl)phenyl]borate (NaBArF) salts. Ligand exchange of [1][BArF] in acetonitrile generated stable [Ru(η5‐C5H5)(CH3CN)3][BArF] ([2][BArF]) complex in high yield. Then, the desired [CpRu(Phen)(CH3CN)] ([3]) complexes were obtained from either the [1] or [2] complex in the presence of the 1,10‐phenanthroline as ligand. For characterization and comparison purposes, the anionic hemilabile ligand TRISPHAT−N (TTN) was introduced on the ruthenium center, from the complex [3][PF6], to quantitatively generate the desired complex [CpRu(Phen)(TTN)] ([4]) by displacement of the remaining acetonitrile ligand and of the PF6− anion. Solid state structures of complexes [1][BArF], [2][BArF], [3][BArF], [3][PF6] and [4] were determined by X‐ray diffraction studies and are discussed herein.

Enantioselective Si-H Insertion Reactions of Diarylcarbenes for the Synthesis of Silicon-Stereogenic Silanes.

We report the first example of enantioselective, intermolecular diarylcarbene insertion into Si-H bonds for the synthesis of silicon-stereogenic silanes. Dirhodium(II) carboxylates catalyze an Si-H insertion using carbenes derived from diazo compounds where selective formation of an enantioenriched silicon center is achieved using prochiral silanes. Fourteen prochiral silanes were evaluated with symmetrical and prochiral diazo reactants to produce a total of 25 novel silanes. Adding an ortho substituent on one phenyl ring of a prochiral diazo enhances enantioselectivity up to 95:5 er with yields up to 98%. Using in situ IR spectroscopy, the impact of the off-cycle azine formation is supported based on the structural dependence for relative rates of diazo decomposition. A catalytic cycle is proposed with Si-H insertion as the rate-determining step, supported by kinetic isotope experiments. Transformations of an enantioenriched silane derived from this method, including selective synthesis of a novel sila-indane, are demonstrated.

One-Step Synthesis of Diaza Macrocycles by Rh(II)-Catalyzed [3 + 6 + 3 + 6] Condensations of Morpholines and α-Diazo-β-ketoesters.

Selective formation of oxonium ylides from morpholines and α-diazo-β-ketoesters was achieved. This was applied to the high-concentration (0.5 M) dirhodium-catalyzed (0.1 mol %) [3 + 6 + 3 + 6] synthesis of 18-membered ring diaza macrocycles (46%-72%). Late-stage functionalization of these derivatives is demonstrated. Mechanistic evidence for a novel (undesired) diazo decomposition pathway is also reported.

Isolation of a Reactive Tricoordinate α-Oxo Gold Carbene Complex.

The [(P,P)Au=C(Ph)CO2 Et]+ complex 3 [where (P,P) is an o-carboranyl diphosphine ligand] was prepared by diazo decomposition at -40 °C. It is the first α-oxo gold carbene complex to be characterized. Its crystallographic structure was determined and DFT calculations have been performed, unraveling the key influence of the chelating (P,P) ligand. The gold center is tricoordinate and the electrophilicity of the carbene center is decreased. Complex 3 mimics transient α-oxo gold carbenes in a series of catalytic transformations, and provides support for the critical role of electrophilicity in the chemoselectivity of phenol functionalization (O-H vs. C-H insertion).

Isolation of a Reactive Tricoordinate α‐Oxo Gold Carbene Complex

AbstractThe [(P,P)Au=C(Ph)CO2Et]+ complex 3 [where (P,P) is an o‐carboranyl diphosphine ligand] was prepared by diazo decomposition at −40 °C. It is the first α‐oxo gold carbene complex to be characterized. Its crystallographic structure was determined and DFT calculations have been performed, unraveling the key influence of the chelating (P,P) ligand. The gold center is tricoordinate and the electrophilicity of the carbene center is decreased. Complex 3 mimics transient α‐oxo gold carbenes in a series of catalytic transformations, and provides support for the critical role of electrophilicity in the chemoselectivity of phenol functionalization (O−H vs. C−H insertion).

Asymmetric Total Syntheses of Kopsia Indole Alkaloids.

The asymmetric total syntheses of a group of structurally complex Kopsia alkaloids, (-)-kopsine, (-)-isokopsine, (+)-methyl chanofruticosinate, (-)-fruticosine, and (-)-kopsanone, has been achieved. The key strategies for the construction of the molecular complexity in the targets included an asymmetric Tsuji-Trost rearrangement to set the first quaternary carbon center at C20, an intramolecular cyclopropanation by diazo decomposition to install the second and third quaternary carbon centers at C2 and C7, respectively, and a SmI2 -promoted acyloin condensation to assemble the isokopsine core. A radical decarboxylation of an isokopsine-type intermediate results in a thermodynamic partial rearrangement to give N-decarbomethoxyisokopsine and N-decarbomethoxykopsine, two key intermediates for the syntheses of Kopsia alkaloids with different subtype core structures.

Asymmetric Total Syntheses of Kopsia Indole Alkaloids

AbstractThe asymmetric total syntheses of a group of structurally complex Kopsia alkaloids, (−)‐kopsine, (−)‐isokopsine, (+)‐methyl chanofruticosinate, (−)‐fruticosine, and (−)‐kopsanone, has been achieved. The key strategies for the construction of the molecular complexity in the targets included an asymmetric Tsuji–Trost rearrangement to set the first quaternary carbon center at C20, an intramolecular cyclopropanation by diazo decomposition to install the second and third quaternary carbon centers at C2 and C7, respectively, and a SmI2‐promoted acyloin condensation to assemble the isokopsine core. A radical decarboxylation of an isokopsine‐type intermediate results in a thermodynamic partial rearrangement to give N‐decarbomethoxyisokopsine and N‐decarbomethoxykopsine, two key intermediates for the syntheses of Kopsia alkaloids with different subtype core structures.

Selective Synthesis of Six Products from a Single Indolyl α-Diazocarbonyl Precursor.

Indolyl α-diazocarbonyls can be selectively cyclized to give six distinct products through the careful choice of catalyst and reaction conditions. A range of catalysts were used, including complexes of Rh(II) , Pd(II) , and Cu(II) , as well as SiO2 , to promote diazo decomposition and subsequent cyclization/rearrangement through a range of mechanistic pathways.

Synthesis of Spiro Ketals, Orthoesters, and Orthocarbonates by CpRu-Catalyzed Decomposition of α-Diazo-β-ketoesters.

Reactions of α-diazo-β-ketoesters with cyclic ketones, lactones, and carbonates are reported. Thanks to the combined use of salt [CpRu(CH3CN)3][BArF] and 1,10-phenanthroline as catalyst for the diazo decomposition, effective and practical syntheses of spiro bicyclic ketals, orthoesters, and orthocarbonates are afforded.

Rapid Generation and Safe Use of Carbenes Enabled by a Novel Flow Protocol with In-line IR spectroscopy.

A powerful new continuous process for the formation and use of donor/acceptor-substituted carbenes is described. The safety profile of diazo group transfer on methyl phenylacetate was determined including kinetic studies in batch and in flow using in-line IR analysis. Batch work-up and liquid chromatography were circumvented by developing an optimized liquid/liquid flow separation method providing aryl diazoacetates in high purity. Fast screening of reaction conditions in flow with in-line IR analysis allowed rapid reaction optimization. Finally, a multistep process of diazo group transfer, extraction, separation and subsequent diazo decomposition combined with multiple X-H insertion reactions was established.

ChemInform Abstract: Regiospecific and Highly Stereoselective Synthesis of β‐Amino (Z)‐Enylphosphonates via β‐Hydrogen Migration Reaction of Dialkyl α‐Diazophosphonates Catalyzed by AgOTf.

A series of dialkyl α-diazophosphonates bearing different substituents have been prepared from natural amino acids in order to investigate the steric effect in 1,2-migration reaction of metal carbenes. The diazo decomposition of the diazophosphonates using the AgOTf/NaBArF complex resulted in β-hydrogen migration to give β-amino (Z)-enylphosphonates in good yields with high regio- and stereoselectivity. A possible reaction mechanism shows that the steric effect could dramatically influence the geometric isomerism aptitude. This new method for constructing (Z)-β-amino vinylphosphonates should be of general utility in organic synthesis.

ChemInform Abstract: Ring‐Expansion Reaction of Isatins with Ethyl Diazoacetate Catalyzed by Dirhodium(II)/DBU Metal‐Organic System: En Route to Viridication Alkaloids.

AbstractA sequential process for the Eistert ring expansion of isatins with ethyl diazoacetate is developed consisting of a DBU‐promoted addition of the diazoester to the isatin 3‐carboxy group followed by Rh(II)‐catalyzed diazo decomposition of the isatin diazo intermediate.