Insertion reactions of macrocyclic rhodium carbenoids: a novel method for the synthesis of cryptands

Reaction of macrocyclic diazocarbonyl compounds and alcohols or diols in the presence of rhodium(II) acetate catalyst led to functionalized macrocyclic di- or tetralactones via O-H insertion. Interestingly, the double O-H insertion reaction with dihydroxy compounds gave cryptands of various ring sizes.     

Anomalous intramolecular C-H insertion reactions of rhodium carbenoids: factors influencing the reaction course and mechanistic implications

The intramolecular insertion of rhodium carbenoids into the alpha-C-H bonds of allylic ethers to give 3(2H)-furanones has been explored. Cyclopropanation is favored irrespective of the complex used for carbenoid generation or the substitution pattern of the allylic ether, unless a substituent is placed on the tether connecting the ether to the alpha-diazo ketone. Unusual acetal products resulting from an anomalous C-H insertion process are obtained in addition to the expected 3(2H)-furanones formed by conventional carbenoid C-H insertion. These acetals are the favored C-H insertion products in certain circumstances and particularly in cases where carbenoid generation is effected using an electron-deficient rhodium complex. Experiments with simple deuterium labeled substrates reveal that anomalous C-H insertion products arise by a mechanism that is distinct from that leading to the formation of conventional C-H insertion products. The formation of acetal products and the outcome of reactions performed using deuterium-labeled substrates suggest that a mechanism involving hydride migration to the rhodium center of the carbenoid is operative.     

Cyclopropyl carbenoid insertion into alkenylzirconocenes—a convergent synthesis of alkenylcyclopropanes and alkylidenecyclopropanes

The insertion of cyclopropyl carbenoids into alkenylzirconocenes, derived by hydrozirconation of terminal alkynes, affords allylzirconium species which react with protons and isonitriles to afford alkenylcyclopropanes, and with aldehydes to afford alkylidene cyclopropanes. The addition of lithium carbenoid to zirconium occurs with the inversion of the organolithium centre.     

A new route to hindered tertiary amines

The Rh(2)(OAc)(4)-stabilized carbenoid derived from dimethyl diazomalonate has been found to insert into the N-H bond of sterically hindered secondary aliphatic amines to afford hindered tertiary aliphatic amines in quite satisfactory yields. For example dimethyl 2-(dicyclohexylamino)propanedioate was formed in 85% yield from dicyclohexylamine, and the severely hindered dimethyl 2-(2,2,6,6-tetramethyl-1-piperidinyl)propanedioate was formed in 38% yield from 2,2,6,6-tetramethylpiperidine. The Rh(2)(OAc)(4) - dimethyl diazomalonate reaction was found to work also for arylalkylamines and diarylamines. In these cases, small amounts of products resulting from formal insertion of the carbenoid into an aromatic C-H bond were detected. Substitution at ortho positions caused the yield of C-H insertion products to increase. Other diazo compounds, viz. ethyl diazoacetoacetate, 2-diazocyclohexane-1,3-dione, and 2-diazo-5,5-dimethylcyclohexane-1,3-dione, performed satisfactorily in Rh(2)(OAc)(4)-catalyzed reactions with arylalkylamines and diarylamines, but led to complicated reaction mixtures with dialkylamines.     

含吡啶环系西佛碱大环配合物和氮杂大环自由配体的合成

2, 6-二羟甲基吡啶(1)经活性MnO~2氧化得到2, 6-二甲酰基吡啶(2)。邻硝基苯酚与N-取代的二(氯乙基)胺在DMF溶液中反应, 得到N-取代的1, 5-二(邻硝基苯氧基)-3-氮杂戊烷(3a～3c), 再经水合肼/Raney Ni还原, 获得N-取代的1, 5-二(邻氨基苯氧基)-3-氮杂戊烷(4a～4c)。利用Ba^2^+作为模板离子, (2)分别与(4a～4c)反应, 合成了一类新的含吡啶环系西佛碱大环配合物I-III, 配合物I、III与NaBH~4的乙醇溶液还原解络, 得到氮杂大环自由配体IV和V。所有西佛碱大环配合物和氮杂大环自由配体均经元素分析、IR、^1H NMR、MS等证实了它们的结构和组成。     

Synthesis, including asymmetric synthesis, of 1-substituted cyclopentenes from cyclobutanones with one-carbon ring-expansion by 1,2-carbon-carbon insertion of magnesium carbenoids

Treatment of 1-chlorovinyl p-tolyl sulfoxides, which were derived from cyclobutanones and chloromethyl p-tolyl sulfoxide, with lithium enolate of tert-butyl carboxylates, amides, lithium α-sulfonyl carbanions, and lithium α-carbanion of acetonitrile gave adducts in high to quantitative yields. The adducts were treated with Grignard regents, such as i-PrMgCl and EtMgCl in toluene to afford 1-substituted cyclopentenes in good to high yields with one-carbon ring-expansion via 1,2-carbon-carbon (1,2-CC) insertion reaction of the generated magnesium carbenoid intermediates. The magnesium carbenoid 1,2-CC insertion was found to be highly stereospecific. When optically pure chloromethyl p-tolyl sulfoxide was used in this procedure, optically active 1-substituted cyclopentenes were obtained in high optical purity.     

Solvent effects in a carbenoid N-H insertion route to triarylamines via 2-diazo-1,3-cyclohexanedione

The Rh-carbenoid derived from 2-diazo-1,3-cyclohexanedione inserts into the N-H bond of arylalkylamines and diarylamines. A solvent for this reactive carbenoid is suggested. The insertion products undergo a Pd-mediated aromatization to afford alkyldiarylamines and triarylamines.     

Synthesis of 2-aminothiazoles via rhodium-catalyzed carbenoid insertion/annulation of sulfoxonium ylides with thioureas

Sulfoxonium ylides as carbene precursors couple smoothly with thioureas in the presence of 5 mol% of rhodium(II) acetate dimmer via carbenoid insertion to afford the corresponding 2-aminothiazoles with high chemoselectivity, providing a facile and efficient approach to access a variety of 2-aminothiazole derivatives with good functional groups tolerance.     

Biomimetic reactions of some macrocyclic diterpenes

Some macrocyclic diterpenes derived from euphohelioscopin A and euphornin have been stereoselectively converted into the jatropholane- and daphnane-type compounds and the known tricyclic compound which has been treated with phCOCl - pyridine to afford euphohelionone, the new type of diterpene isolated from euphorbia helioscopia L.     

Syntheses of novel 4-tert-alkyl ether proline-based 16- and 17-membered macrocyclic compounds

Starting from N-Cbz-4-hydroxyproline methyl ester 1, a boron trifluoride-diethyl etherate-catalyzed reaction provided 4-tert-alkyl ether proline 4. Two deprotections and amide bond formations furnished the phenol alcohol 2. The macrocyclization of 2 was accomplished through a Mitsunobu reaction using triphenylphosphine and 1,1'-(azodicarbonyl)dipiperidine (ADDP), to afford novel 16- and 17-membered proline-based macrocyclic compounds of type 3.     

A method for the synthesis of cyclopropanes by regiospecific and regioselective magnesium carbenoid 1,3-CH insertion as the key reactions

Addition reaction of two geometrical isomers of 1-chlorovinyl p-tolyl sulfoxides, derived from unsymmetrical ketones and chloromethyl p-tolyl sulfoxide, with lithium enolate of tert-butyl acetate gave single diastereomers of the adduct, respectively. Treatment of each diastereomer with i-PrMgCl resulted in the formation of magnesium carbenoid. Highly regiospecific 1,3-CH insertion reaction was found to take place from each magnesium carbenoid to afford cyclopropanes. On the other hand, when the unsymmetrical ketones bearing an oxygen- or a nitrogen-functional group on the α-carbon were used in this procedure, the regioselective 1,3-CH insertion reaction proceeded mainly. Stereochemistry of the adducts, reaction mechanism, and essence of the specificity and the selectivity are discussed.     

Binuclear and polynuclear transition metal complexes with macrocyclic ligands. 3. New polydentate macrocyclic ligands in reactions of 4-alkyl-2,6-diformylphenols with 1,2-diaminobenzenes

The mechanism of abnormal condensation of 2,6-diformyl-4-R-phenols with 1,2-diaminobenzenes accompanied by the reduction of two of four double C=N bonds in macrocyclic Schiff"s bases formed was studied by DFT (gradient-corrected PBE functional, TZ2p basis set). In the first step, [1+1] Schiff"s base is formed and disproportionates further to afford amine and benzoimidazolylphenols. Two new macrocyclic polydentate ligands containing two CH₂—NH moieties in the rings were synthesized. The reduction of one of these ligands with sodium borohydride gave the new macrocyclic ligand, whose structure and conformations were studied by the DFT method.     

Binuclear and polynuclear transition metal complexes with macrocyclic ligands. 5. Novel complexes of asymmetric polydentate macrocyclic Schiff bases. Step-by-step synthesis

Reactions of 2,6-bis(3-aminopropylaminocarbonyl)pyridine (1) with 4-tert-butyl-2,6-diformylphenol and 2,5-diformylpyrrole in the presence of Ba(ClO₄)₂ in EtOH afford barium complexes with asymmetric macrocyclic Schiff bases as soft and hard ligands. The reaction of compound 1 with Cu(OCOCMe₃)₂ involves closure of a tetrahydropyrimidine ring to give a mononuclear complex, which was structurally characterized by X-ray diffraction analysis.     

Thermal Cyclization of Copper Carbenoid of α‐Dizao α‐Phosphorylacetate: Unexpected and Novel Access to Oxaphosphirane

Under the catalysis of Cu(OTf)₂ in refluxing CH₂Cl₂, ethyl α‐dizao α‐(diethylphosphoryl)acetate was shown to undergo a new cyclization reaction to afford a pentacovalent oxaphosphirane product. The reaction is proposed to occur through the addition of the P=O double bond to the copper carbenoid, followed by the hydrolysis of the ylide intermediate. Our finding represents the first example on producing oxaphosphiranes from dizao phosphoryl compounds. On the other hand, the corresponding rhodium carbenoid displayed the different reactivity under the same thermal conditions, to produce the β‐propiolactone through the well‐recognized C‐H insertion pathway.     

High stereoselective preparation of O-protected 2-trifluoromethyl 3-bromoallylic alcohols from 1,1-dibromo-1-alkenes

A highly stereoselective lithium-bromine exchange reaction of 2-trifluoromethyl-3,3-dibromoallylic alcohols is described. (E)- and (Z)-2-trifluoro-3-bromoallylic alcohols were obtained in THF and hexane, respectively. The lithium carbenoid intermediate was stable even at -40 degrees C and could be trapped by various electrophiles to afford functionalized 2-trifluoromethyl-3-bromoallylic alcohols. [reaction: see text]     

Ruthenium-catalyzed stereoselective intramolecular carbenoid C-H insertion for beta- and gamma-lactam formations by decomposition of alpha-diazoacetamides

[reaction: see text] An operationally simple catalytic system based on [RuCl(2)(p-cymene)(2)] was developed for stereoselective cyclization of alpha-diazoacetamides by intramolecular carbenoid C-H insertion, and beta-lactams were produced in excellent yields and >99% cis-stereoselectivity. The Ru-catalyzed reactions can be performed without the need for slow addition of diazo compounds and inert atmosphere. With alpha-diazoanilides as substrate, the carbenoid insertion was directed selectively to aromatic C-H bond leading to gamma-lactam formation (>95% yield).     

Synthetic studies toward sarain A. Formation of the western macrocyclic ring

Starting with the tricyclic core 2b, annulation to form the 13-membered western ring of sarain A has been achieved to afford the macrocycle 30a by initial construction of the sterically congested quaternary center at C-3, followed by elaboration of the C-3 side-chain and ring-closing olefin metathesis. Also included is a parallel conversion of tricycle 2c to macrocycle 30b containing a functionalized side-chain at N-1 suitable for attachment of the eastern macrocyclic ring.     

Synthesis of chiral linear and macrocyclic candidates: VI. Synthesis and antibacterial activity of some macrocyclic tripeptides and linear dipeptide Schiff bases

A series of macrocyclic tripeptides and linear dipeptide Schiff base derivatives has been synthesized using pyridine-3,5-dicarboxylic acid and L-phenyalanine methyl ester as starting materials. Treatment of pyridine-3,5-dicarbonyl dichloride with L-phenylalanine methyl ester gave N,N′-(pyridine-3,5-diyldicarbonyl)bis(L-phenyalanine methyl ester) which was hydrolyzed with 1N sodium hydroxide to the corresponding bis-acid, and the latter was cyclized with diamino acids to afford macrocyclic tripeptide derivatives. The reaction of the bis ester with hydrazine hydrate gave bis-hydrazide, which was condensed with aldehydes to obtain the corresponding Schiff base derivatives. The structures of the newly synthesized compounds were confirmed by IR, ¹H and ¹³C NMR, and MS spectral data and elemental analyses. The antimicrobial activities of some of the newly synthesized compounds were comparable with that of Streptomycin used as control.     

Synthesis and molecular orbital calculations of some benzo-substituted macrocyclic diamides and their corresponding macrocyclic dithiodiamides

A new series of benzo-substituted macrocyclic diamides were prepared by nucleophilic reaction of the appropriate dipotassium salts with the corresponding bis(halo) compounds in refluxing DMF. Treatment of the novel macrocyclic diamides with Lawesson's reagent in refluxing toluene led to the formation of the corresponding macrocyclic dithiodiamides in good yields. Molecular orbital calculations were performed at the semi-empirical level AM1 on some of the studied macrocycles. Thermodynamic functions show that the most stable structures in gas phase that have internal amine groups are less in energy than the other ones that have internal carbonyl groups. The solvent polarity does not appreciably affect the stability trend of the three conformers of each compound due to their comparable dipole moments. A complete and thorough survey of proton affinity (PA) and proton detachment energies (PDE) on each of the possible sites has been performed.     

A versatile synthesis, including asymmetric synthesis, of bicyclo[n.1.0]alkanes from cyclic ketones via the magnesium carbenoid 1,3-CH insertion as a key reaction

Treatment of 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from various cyclic ketones and chloromethyl p-tolyl sulfoxide in three steps, in high yields, with lithium enolate of tert-butyl acetate or its homologues gave the adducts in quantitative yields. The adducts were treated with isopropylmagnesium chloride in ether in dry toluene as the reaction solvent to afford bicyclo[n.1.0]alkanes in high to quantitative yields via magnesium carbenoid 1,3-CH insertion. When this method was carried out starting from unsymmetrical cyclic ketones and (R)-chloromethyl p-tolyl sulfoxide, an asymmetric synthesis of bicyclo[n.1.0]alkane was realized.