Carbonyl Migration Research Articles

Carbonyl Migration in Uronates Affords a Potential Prebiotic Pathway for Pentose Production.

Carbohydrate biosynthesis is fundamental to modern terrestrial biochemistry, but how this collection of metabolic pathways originated remains an open question. Prebiotic sugar synthesis has focused primarily on the formose reaction and Kiliani-Fischer homologation; however, how they can transition to extant biochemical pathways has not been studied. Herein, a nonenzymatic pathway for pentose production with similar chemical transformations as those of the pentose phosphate pathway is demonstrated. Starting from a C6 aldonate, namely, gluconate, nonselective chemical oxidation yields a mixture of 2-oxo-, 4-oxo-, 5-oxo-, and 6-oxo-uronate regioisomers. Regardless at which carbinol the oxidation takes place, carbonyl migration enables β-decarboxylation to yield pentoses. In comparison, the pentose phosphate pathway selectively oxidizes 6-phosphogluconate to afford the 3-oxo-uronate derivative, which undergoes facile subsequent β-decarboxylation and carbonyl migration to afford ribose 5-phosphate. The similarities between these two pathways and the potential implications for prebiotic chemistry and protometabolism are discussed.

Polyhedral Ferraboranes with Iron Carbonyl Vertices: Carbonyl Migration Processes in the Iron Tetracarbonyl Derivatives.

The structures and energetics of the neutral Bn-1Hn-1Fe(CO)x (x = 4, 3) and the dianions [Bn-1Hn-1Fe(CO)3]2- (n = 6-14) have been investigated by density functional theory. The low-energy structures of the tricarbonyl dianions [Bn-1Hn-1Fe(CO)3]2- are all found to have closo deltahedral structures in accordance with their 2n+2 skeletal electrons. The low-energy structures of the neutral tricarbonyls Bn-1Hn-1Fe(CO)3 (n = 6-14) with only 2n skeletal electrons are based on capped (n-1)-vertex closo deltahedra (n = 6, 7, 8) or isocloso deltahedra with a degree 6 vertex for the iron atom. The closo 8- and 9-vertex deltahedra are also found in low-energy Bn-1Hn-1Fe(CO)3 structures relating to the nondegeneracy of their frontier molecular orbitals. Carbonyl migration occurs in most of the low-energy structures of the tetracarbonyls Bn-1Hn-1Fe(CO)4. Thus, migration of a carbonyl group from an iron atom to a boron atom gives closo Bn-2Hn-2(BCO)(μ-H)Fe(CO)3 structures with a BCO vertex and a hydrogen atom bridging a B-B deltahedral edge. In other low-energy Bn-1Hn-1Fe(CO)4 structures, a carbonyl group is inserted into the central n-vertex FeBn-1 deltahedron to give a Bn-1Hn-1(CO)Fe(CO)3 structure with a central (n+1)-vertex FeCBn-1 deltahedron that can be an isocloso deltahedron or a μ3-BH face-capped n-vertex FeCBn-2 closo deltahedron. Other low-energy Bn-1Hn-1Fe(CO)4 structures include Bn-1Hn-1Fe(CO)2(μ-CO)2 structures with two of the carbonyl groups bridging FeB2 faces (n = 6, 7, 10) or Fe-B edges (n = 12) or structures in which a closo Bn-1Hn-1 ligand (n = 6, 7, 10, 12) is bonded to an Fe(CO)4 unit with exclusively terminal carbonyl groups through B-H-Fe bridges.

Origins of Catalyst-Controlled Chemoselectivity in Transition-Metal-Catalyzed Divergent Epoxide Conversion

Transition-metal-catalyzed transformation reactions of epoxides can provide practical C2 synthons in synthetic chemistry. These reactions offer a feasible strategy for catalyst-controlled epoxide divergent transformations. Therefore, finding out the crucial factors controlling chemoselectivity is the key to the rational design of transition-metal-catalyzed divergent conversions with high selectivity. In these studies, we have selected and systematically explored the general mechanism of both Mn(CO)5–- and Co(CO)4–-catalyzed divergent epoxide transformations associated with different products, namely, alkenes and β-lactones. Our computational studies showed that the chemoselective reaction undergoes either a retro-[3 + 2] step forming an alkene or a carbonyl migration insertion step for generating a β-lactone. For the Mn-catalyzed reaction, the energy barrier of the retro-[3 + 2] step is lower than that of the carbonyl migration insertion step, but the case is reversed in the Co-catalyzed reaction. Further analysis revealed that the spatial configurations of metal complexes and Pauli repulsion controlled by the metal atomic radius could be responsible for the phenomenon. The insights obtained are not only important for understanding chemoselectivity determined by the inherent properties of transition metals but also provide a valuable case for studying transition-metal-catalyzed reactions with catalyst-controlled chemoselectivity.

Synthesis of Unnatural α-Amino Acids from (Pyridin-2-yl) Carbamate via CIPE-Induced Carbonyl Migration.

Synthetic methods of unnatural α-amino acids have always been the focus of extensive research due to their significant bioactivities. However, convenient transition-metal-free catalyzed methods are still in demand. Herein, we report a novel strategy for the construction of an unnatural α-amino acid skeleton via intramolecular rearrangement of carbamates, which are readily available from amines and their common protecting groups. This rearrangement could afford a variety of amino ester products in up to 98% yield, even in gram-scale reaction. The reaction mechanism was studied in detail through experiments and theoretical calculations. The complex-induced proximity effect (CIPE) from the 2-pyridyl group is shown to be indispensable for this transformation.

Metal-free hypervalent iodine-promoted tandem carbonyl migration and unactivated C(Ph)-C(Alkyl) bond cleavage for quinolone scaffold synthesis.

An unexpected iodine(III)-mediated C(sp3)-C(sp2) bond cleavage of 3-(methylamino)-2-(2-substitutedbenzoyl)acrylates for efficient synthesis of privileged scaffold 4-quinolones was described. Notably, a wide range of alkyl groups (e.g. methyl, tert-butyl or alkyl chain) can be conveniently cleaved in this system. The detailed mechanism studies revealed that the transformation proceeded through cascade ipso-cyclization and 1,2-carbonyl migration, the smaller bond energy determined ortho C-C bond cleavage rather than C-H bond cleavage, via an enamine radical intermediate.

Access to and Reactivity of Fe0, Fe−I, FeI, and FeII PCcarbeneP Pincer Complexes

AbstractDespite their promising metal–ligand cooperative reactivity, PCcarbeneP pincer ligands are rarely reported for first‐row transition‐metal centres. Using a dehydration methodology, we report access to an Fe0 PCcarbeneP pincer complex (1) that proceeds via an isolated α‐hydroxylalkyl hydrido complex (3). Reversible carbonyl migration to the carbene position in 1 is found to allow coordination chemistry and E−H bond addition (E=H, B, Cl) across the iron–carbene linkage, representing a unique mechanism for metal–ligand cooperativity. The PCcarbeneP pincer ligand is also found to stabilize formal FeII, FeI, and Fe−I oxidation states, as demonstrated with synthesis and characterization of the complexes [11‐X][BArF20] (X=Br, I), 12, and K[13]. Compound K[13] is found to be highly reactive, and abstracts hydrogen from a range of aliphatic C−H sources. Computational analysis by DFT suggests that the formal FeI and Fe−I complexes contain significant carbene radical character. The ability of the PCcarbeneP ligand scaffold to partake in metal–ligand cooperativity and to support a range of iron oxidation states renders it as potentially useful in many catalytic applications.

Access to and Reactivity of Fe0 , Fe-I , FeI , and FeII PCcarbene P Pincer Complexes.

Despite their promising metal-ligand cooperative reactivity, PCcarbene P pincer ligands are rarely reported for first-row transition-metal centres. Using a dehydration methodology, we report access to an Fe0 PCcarbene P pincer complex (1) that proceeds via an isolated α-hydroxylalkyl hydrido complex (3). Reversible carbonyl migration to the carbene position in 1 is found to allow coordination chemistry and E-H bond addition (E=H, B, Cl) across the iron-carbene linkage, representing a unique mechanism for metal-ligand cooperativity. The PCcarbene P pincer ligand is also found to stabilize formal FeII , FeI , and Fe-I oxidation states, as demonstrated with synthesis and characterization of the complexes [11-X][BArF 20 ] (X=Br, I), 12, and K[13]. Compound K[13] is found to be highly reactive, and abstracts hydrogen from a range of aliphatic C-H sources. Computational analysis by DFT suggests that the formal FeI and Fe-I complexes contain significant carbene radical character. The ability of the PCcarbene P ligand scaffold to partake in metal-ligand cooperativity and to support a range of iron oxidation states renders it as potentially useful in many catalytic applications.

Unusual effects of the bulky 1-norbornyl group in cobalt carbonyl chemistry: low-energy structures with agostic hydrogen atoms

Low-energy (nor)Co(CO)n (n = 3, 2) and (nor)2Co2(CO)n (nor = 1-norbornyl; n = 6, 5) structures are found to have agostic hydrogen atoms from a CH2 group adjacent to the Co–C bond forming C–H–Co bridges. In addition, low-energy structures are found with (nor)CO acyl ligands resulting from carbonyl migration.

Carbonyl migration from phosphorus to the metal in binuclear phosphaketenyl metal carbonyl complexes to give bridging diphosphido complexes

Carbonyl groups from bridging phosphaketenyl ligands in Mn2(CO)8(μ-PCO)2 are predicted to migrate from phosphorus to manganese upon decarbonylation, giving the diphosphido Mn2(CO)n+2(μ-P2) derivatives.

The synthesis and photolysis mechanisms of 8-nitroquinoline-based photolabile caging groups for carboxylic acid

Photolabile protecting groups have been extensively studied and applied for protection of small biological molecules, which make it convenient to detect the biological processes of the caged compounds. In this study, a series of 8-nitroquinoline-based photolabile caging groups for carboxylic acid were synthesized with improved photolysis efficiency. Among them, 6-bromo-8-nitro-1, 2-dihydroquinolinyl chromophore was proven the best derivative on account of its longest absorption wavelength (345 nm), highest caging ability, and quantum yield (Φ = 0.003). Moreover, density functional theory calculations were performed in order to study the photolysis mechanisms. Theoretical calculations revealed that the reaction was kinetically inert under general mild condition with the high barrier height of 34.3 kcal/mol at carbonyl migration step, while under the photolysis condition, because of the large energy gap (64.5 kcal/mol) between S0 and S1 states, the reaction should be accessible in the triplet ground state (T1) through successive excitation of S0 S1 states, subsequent intersystem crossing of S1 T1 states, and finally returned to the stable S0 state for product via potential energy surface crossing between T1 and S0 states. Copyright © 2014 John Wiley & Sons, Ltd.

ChemInform Abstract: Gold‐Catalysis: Highly Efficient and Regio‐Selective Carbonyl Migration in Alkynyl‐Substituted Indole‐3‐carboxamides Leading to Azepino[3,4‐b]indol‐1‐ones.

An unprecedented rearrangement/anellation sequence allows the clean synthesis of azepino[3,4-b]indol-1-ones from readily available starting materials. Alkyne-substituted indole-3-carboxamides were prepared and converted to azepino[3,4-b]indol-1-ones by the SPhosAuNTf2 catalyst (SPhos=2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl). The new connectivity, which involves an unprecedented 3,2-shift of an acylamino group for the product formation, was proven by a crystal structure analysis.

Gold‐Catalysis: Highly Efficient and Regio‐Selective Carbonyl Migration in Alkynyl‐Substituted Indole‐3‐Carboxamides Leading to Azepino[3,4‐b]indol‐1‐ones

AbstractAn unprecedented rearrangement/anellation sequence allows the clean synthesis of azepino[3,4‐b]indol‐1‐ones from readily available starting materials. Alkyne‐substituted indole‐3‐carboxamides were prepared and converted to azepino[3,4‐b]indol‐1‐ones by the SPhosAuNTf2 catalyst (SPhos=2‐dicyclohexylphosphino‐2′,6′‐dimethoxybiphenyl). The new connectivity, which involves an unprecedented 3,2‐shift of an acylamino group for the product formation, was proven by a crystal structure analysis.

Asymmetric Carbonyl Migration of α-Amino Acid Derivatives via Memory of Chirality

N-tert-Butoxycarbonylcarbamates of α-amino acid derivatives underwent asymmetric carbonyl migration by treatment with KHMDS in DMF to give α-amino acid derivatives with an additional ester group at the newly formed tetrasubstituted carbon center in up to 99% ee.

Cationic rhodium(I) complex-catalyzed σ- and π-bond activation cascade: Isomerization of allyl propargyl ethers to allenic aldehydes and dienals

A cationic rhodium(I)/1,1'-bis(diphenylphosphino)ferrocene (dppf) complex catalyzes isomerization of allyl propargyl ethers to allenic aldehydes in good yields at room temperature 40 °C. At 80 °C, carbonyl migration from allenic aldehydes proceeds further to give dienals in good yields. The cationic rhodium(I)/dppf complex acts as a dual catalyst for activation of σ- and π-bonds in these isomerization reactions.

Platinum-Catalyzed Synthesis of Pyrrolo[3,2-c]azepin-4-ones

Aiming to synthesize new pyrrolo[2,3-c]azepin-8-one derivatives 4 from the ­Sonogashira product 2 of the acetylenic pyrrole 1 under gold or platinum catalysis, Beller and co-workers unexpectedly obtained the isomeric pyrrolo[2,3-c]azepin-4-ones. Thus, instead of the expected endo-dig cyclization of 2 to give 4, the presumed initial acetylenic gold(III) or platinum(IV) complex undergoes C2 to C3 carbonyl migration prior to the alternative C2 endo-dig cyclization to yield the isomer 3. The reaction proceeds in the presence of AuCl3 or H2PtCl6˙6H2O, with H2PtCl6˙6H2O giving the best results. Alkynes with R = Ar gave moderate to good yields of products, whereas heteroaromatic-substituted alkynes led to poorer yields.

Cationic Rhodium(I)−dppf Complex-Catalyzed Olefin Isomerization/Propargyl Claisen Rearrangement/Carbonyl Migration Cascade

We have established that a cationic rhodium(I)-dppf complex catalyzes isomerizations of allyl propargyl ethers to allenic aldehydes in good yields from room temperature to 40 degrees C. On the other hand, carbonyl migration reactions from allenic aldehydes further proceed to give dienals in good yields at 80 degrees C.

Chemistry of Unsaturated Group 6 Metal Complexes with Bridging Hydroxy and Methoxycarbyne Ligands. 5. Heterometallic Clusters Derived from the Neutral Complex [Mo2(η5-C5H5)2(μ-COMe)(μ-PCy2)(μ-CO)

The unsaturated complex [Mo2Cp2(μ-COMe)(μ-PCy2)(μ-CO)] (1) reacts with the solvate manganese complexes [MnL(CO)2(THF)] (L = Cp, η5-C5H4Me) rapidly at room temperature in toluene solution to give the corresponding electron-precise clusters [MnMo2Cp2L(μ3-COMe)(μ-PCy2)(CO)4] (Mo−Mo = 2.986(1) Å when L = Cp), which follow from the addition of the manganese fragment to compound 1 and further spontaneous carbonylation. In contrast, the incorporation of the group 8 metal fragments M(CO)4 occurs selectively either at room temperature (reaction with [Fe2(CO)9]) or under photochemical activation (reaction with [Ru3(CO)12]) to give the 46-electron derivatives [Mo2MCp2(μ3-COMe)(μ-PCy2)(CO)5] (M = Fe, Ru), which follow from the addition of the M(CO)4 fragment to compound 1 and carbonyl migration from M to molybdenum. Simple addition of a metal fragment to the triple intermetallic bond of 1 is observed in its reaction with CuCl, which gives the unsaturated derivative [CuMo2ClCp2(μ3-COMe)(μ-PCy2)(μ-CO)]. Compound 1 can also yield tetranuclear derivatives. Thus, it reacts with [Co2(CO)8] at room temperature to give a mixture of the clusters [Co2Mo2Cp2(μ3-COMe)(μ-PCy2)(μ-CO)2(CO)4] and [Co2Mo2Cp2(μ3-COMe)(μ-PCy2)(μ-CO)(CO)6]. The heptacarbonyl compound has the expected composition, i.e., the one resulting from the addition of a Co2(CO)6 fragment to compound 1, but not the expected structure, since the PCy2 ligand is found as bridging one Mo−Co edge of the tetrahedral metal core, according to an X-ray diffraction study. In contrast, the hexacarbonyl cluster roughly has the expected structure, but has one carbonyl below the number that might have been anticipated, with the resulting unsaturation being mainly located at the Mo−Mo bond (2.686(1) Å) of this tetrahedral cluster.

Probing the catalytic mechanism of S-ribosylhomocysteinase (LuxS) with catalytic intermediates and substrate analogues.

S-Ribosylhomocysteinase (LuxS) cleaves the thioether bond in S-ribosylhomocysteine (SRH) to produce homocysteine (Hcys) and 4,5-dihydroxy-2,3-pentanedione (DPD), the precursor of the type II bacterial quorum sensing molecule (AI-2). The catalytic mechanism of LuxS comprises three distinct reaction steps. The first step involves carbonyl migration from the C1 carbon of ribose to C2 and the formation of a 2-ketone intermediate. The second step shifts the C=O group from the C2 to C3 position to produce a 3-ketone intermediate. In the final step, the 3-ketone intermediate undergoes a beta-elimination reaction resulting in the cleavage of the thioether bond. In this work, the 3-ketone intermediate was chemically synthesized and shown to be chemically and kinetically competent in the LuxS catalytic pathway. Substrate analogues halogenated at the C3 position of ribose were synthesized and reacted as time-dependent inhibitors of LuxS. The time dependence was caused by enzyme-catalyzed elimination of halide ions. Examination of the kinetics of halide release and decay of the 3-ketone intermediate catalyzed by wild-type and mutant LuxS enzymes revealed that Cys-84 is the general base responsible for proton abstraction in the three reaction steps, whereas Glu-57 likely facilitates substrate binding and proton transfer during catalysis.

Carbohydrate pyrolysis mechanisms from isotopic labeling: Part 2. The pyrolysis of d-glucose: General disconnective analysis and the formation of C 1 and C 2 carbonyl compounds by electrocyclic fragmentation mechanisms

The flash pyrolysis of d-glucose was investigated by the use of isotopic labeling with 13C, in conjunction with GC/MS. Co-pyrolysis of uniformly labeled and unlabeled d-glucose established the extent of unimolecular formation of each of the pyrolysis products. A complete set of singly labeled d-glucose isotopologs was used to determine the origin of specific carbons within each of the pyrolysis products. The Cyclic Grob 1,3-diol fragmentation and the tandem alkaline pinacol rearrangement/retro-aldol fragmentation (TAPRRAF) discovered from the pyrolysis of glycerin were applied to the analysis of pyrolytic fragmentation pathways for d-glucose. These mechanisms provide means of initial carbon–carbon bond breakage, and are consistent with the high proportion of carbon-unimolecularity observed for many of the volatile low-molecular weight products of the reaction. These and other reactions, including the retro-aldol fragmentation, carbonyl migration, dehydration, ene-reaction, retro-Claisen cleavage, hydrolysis, or alcoholysis were applied conceptually to the initial fragments resulting from either mechanism to ascertain the ultimate fate of the carbons of d-glucose. The “predicted” results were then compared with labeling patterns observed by experiment. The most promising rationalizations provided by this exercise are presented herein, for the formation of five C 1 and C 2 carbonyl-containing pyrolysis products: formaldehyde, formic acid, acetaldehyde, glycolaldehyde and acetic acid.

Synthesis of Indazoles by the [3+2] Cycloaddition of Diazo Compounds with Arynes and Subsequent Acyl Migration

The [3+2] cycloaddition of a variety of diazo compounds with o-(trimethylsilyl)aryl triflates in the presence of CsF or TBAF at room temperature provides a very direct, efficient approach to a wide range of potentially biologically and pharmaceutically interesting substituted indazoles in good to excellent yields under mild reaction conditions. Simple diazomethane derivatives afford N-unsubstituted indazoles or 1-arylated indazoles, depending upon the stoichiometry of the reagents and the reaction conditions, while dicarbonyl-containing diazo compounds undergo carbonyl migration to afford 1-acyl or 1-alkoxycarbonyl indazoles selectively.