Intramolecular CH Insertion Research Articles

Amine-mediated synthesis of amides from 1,3-dicarbonyl compounds through a domino diazo transfer/aminolysis process

The dual role of amines as both catalysts and substrates for the synthesis of diazo compounds or carboxamides from 1,3-dicarbonyl compounds is described herein. In the presence of a suitable diazo transfer agent, primary and cyclic secondary amines act as basic catalysts for the diazo transfer reaction to malonates, β-keto esters, and β-diketones. Depending on the structure of the 1,3-dicarbonyl compound and the nucleophilicity of the amine, the resulting α-diazo-β-keto ester undergoes cleavage of the acyl group to give amides. A multifunctionalized γ-azido-α-diazo-β-keto ester was cleanly prepared in good yields by this one-pot protocol under practical and safe conditions, being employed in a Knoevenagel-type condensation with aromatic aldehydes to give densely functionalized diazo azido compounds. Further treatment of these unsaturated γ-azido-α-diazo-β-keto esters with primary amines readily furnished the corresponding α-azidocinnamamides in high yields, which were used in the synthesis of novel indole-2-carboxamides through the rhodium-catalyzed intramolecular CH insertion.

Specific intramolecular aromatic C[sbnd]H insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp3)−H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp2)−H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp2)−H and aliphatic 1,5- and 1,6-C(sp3)−H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp3)−H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp2)−H insertion.

ChemInform Abstract: Versatile Donor—Acceptor Cyclopropenes in Metal Carbene Transformations

AbstractReview: [28 refs.

Synthesis, structure and pyrolysis of stabilised phosphonium ylides containing saturated oxygen heterocycles.

A range of twelve stabilised phosphonium ylides containing tetrahydrofuran, tetrahydropyran or 2,2-dimethyl-1,3-dioxolane rings have been prepared and fully characterised, including one X-ray structure determination of each type. The X-ray structures confirm the P=C and C=O functions to be syn and all the compounds undergo thermal extrusion of Ph3PO to give the corresponding alkynes. In some cases there is also competing loss of Ph3P to give different carbene-derived products and evidence has been obtained for the generation of 2-phenyloxete in this way. Raising the pyrolysis temperature leads in several cases to new secondary reactions of the alkyne products involving a sequence of alkyne to vinylidene isomerisation, intramolecular CH insertion, and retro Diels Alder reaction.

Mechanistic studies of intramolecular CH insertion reaction of arylnitrenes: isotope effect, configurational purity and radical clock studies

AbstractIn order to reveal the mechanism of the intramolecular CH insertion of arylnitrenes, three experiments were carried out: measurement of isotope effects, determination of the extent of configurational retention and radical clock studies. Irradiation of the deuterium‐substituted azide 4‐d in an inert solvent exclusively afforded the indolines 5‐h and 5‐d, in which the kinetic isotope effect kH/kD on the intramolecular CH insertion of the nitrene was evaluated as 12.6–14.7 at room temperature. A chiral chromatographic analysis of the indoline 11 obtained from the optically active azide (S)‐6 revealed that the enantiomeric purity of the starting azide was almost completely lost during the intramolecular CH insertion of the photolytically generated nitrene (enantiomeric excess <10%). The thermolysis of the azide 7 at 180°C mainly gave a mixture of the cyclopropyl ring‐opened products 20–22, together with the intramolecular CH insertion product with an intact cyclopropyl ring 19. On the basis of these observations, we concluded that the intramolecular CH insertion of the nitrene proceeds primarily by the hydrogen abstraction–recombination mechanism. We propose, however, a small contribution of the concerted mechanism to the intramolecular CH insertion, based on the solvent dependence of the isotope effect and the extent of the configurational retention. Copyright © 2004 John Wiley & Sons, Ltd.

The Enantioselectivity and the Stereochemical Course of Copper-Catalyzed Intramolecular CH Insertions of Phenyliodonium Ylides

The Cu-catalyzed intramolecular CH insertion of phenyliodonium ylide 1b was investigated at 0° in the presence of several chiral ligands. Enantioselectivities varied in the range 38–72%, and were higher than those resulting from reaction of the diazo compound 1c at 65°. The intramolecular insertion of the enantiomerically pure methyl diazoacetate (R)-20 and of the corresponding phenyliodonium ylide (R)-21 proceeded to (R)-23 with retention of configuration with [Cu(hfa)2] (hfa=hexafluoroacetylacetone=1,1,1,5,5,5-hexafluoropentane-2,4-dione) and [Rh2(OAc)4]. These results are consistent with a carbenoid mechanism for the Cu-catalyzed insertion with phenyliodonium ylides. However, the insertion of the perfluorosulfonated phenyliodonium ylide (R)-29 afforded with [Cu(hfa)2] as well as with [Rh2(OAc)4] the cyclopentanone derivative 30 as a cis/trans mixture with only 56–67% enantiomeric excess.

Enantioselective Intramolecular CH-Insertions upon Cu-Catalyzed Decomposition of Phenyliodonium Ylides

The Cu-catalyzed intramolecular CH insertion of phenyliodonium ylide 5b has been investigated at 0° C in the presence of several chiral ligands. Enantioselectivities vary in the range of 38–72 %, and are higher than those resulting from reaction of the diazo compound 5c at 65° C. The results are consistent with a carbenoid mechanism for Cu-catalyzed decomposition of phenyliodonium ylides.

Reações de inserção intramolecular de diazo compostos polifuncionais catalisadas por ródio(II): síntese de oxetan-3-ona-2-carboxilato e outros heterociclos funcionalizados

g-Hydroxy-a-diazo-b-ketoesters are key intermediates in the chemistry of penicilin-based antibiotics and natural products. The method developed here for the synthesis of ethyl 2-diazo-4-hydroxy-3-oxo-butanoate 17 (in two steps from the diazo mercurial 2) compares very favorably with those reported in the literature for similar compounds. The Rh2(OAc)4-mediated intramolecular OH-insertion reaction of the diazo hydroxy ester 17 was investigated, furnishing the oxetan-3-one-2-carboxilate 18 in good yield. When the diazo ester lacks a free hydroxyl group as in the case of the phenoxy diazo ester 11 an intramolecular CH-insertion takes place, affording the 2H-chromene 20 in almost quantitative yield. The behavior of other functionalized diazo esters towards Rh2(OAc)4 was also investigated.

Carbene−Bridgehead Olefin−Carbene Rearrangement: Formation of the Tetracyclo[4.3.0.02,8.04,7]nonane Skeleton by Carbene CH Insertion1

The sequence of rearrangements of carbenes 6 has been studied. Precursors for 6 were 1-halo-3-(n-halomethyl)bicyclo[1.1.1]pentane derivatives 11, which were obtained by addition of polyhalomethanes to the central bond of [1.1.1]propellane derivative 13 via radical chain processes. Reaction of compounds 11 with MeLi or sodium bis(trimethylsilyl)amide generates carbenes 6, which are stabilized by a carbene (6)−bridgehead olefin−carbene (9) rearrangement, followed by an intramolecular CH insertion reaction of carbenes 9 to afford tetracyclononane derivatives 15 in good yields. The carbenes 6 show only slight preferences in the rearrangement to alkenes 7 and 8. Both could be trapped with α-methylstyrene as ene adducts 16 and 17. The strongly twisted bridgehead olefin 7 has only the option to rearrange to carbene 9, whereas 8 could give 9 or 10, but prefers to give 9, in accordance with results of DFT calculations. The tetracyclononanes 15c and 15d contain halide atoms in the 1,3-positions; on treatment with t...

The Inferior p-Donor Ability of Phosphanyl versus Amino Substituents: Consequences on the Stability and Reactivity of Phosphanyl- and Aminocarbenes

Bis(diisopropylamino)(trimethylstannyl)phosphane (2) reacts with the (chloromethylene)diisopropylammonium salt 1 affording the C-phosphanyl-substituted iminium salt 3 (67 % yield), which features a short C–N (1.284 A) and a long P–C bond (1.850 A), a planar iminium nitrogen atom and a pyramidalized phosphorus atom. Deprotonation of 3 leads to the enamine 8 (92 % yield), while addition of sodium methoxide followed by thermolysis of the resulting hemiaminal 9 (90 % yield) gives rise to the azaphosphetane 10 (85 % yield), by intramolecular CH insertion of the transiently formed (amino)(phosphanyl)carbene 6.

Large Deuterium Isotope Effects for Intramolecular CH Insertion Reaction of 2-Alkylphenylnitrenes

Abstract The deuterium isotope effect for the intramolecular CH insertion reaction of the nitrene photolytically generated from 2-(2-phenylethyl)phenyl azide in cyclohexane is obtained as 14.7 ± 0.3 at 20 °C, which supports the hydrogen abstraction-recombination mechanism involving the triplet state nitrene. The temperature dependence of the isotope effect suggests the operation of the tunneling of the hydrogen atom in this process.

Flash vacuum pyrolysis of dichlorophosphines over magnesium: Generation and reactivity of simple phosphinidenes

Flash vacuum pyrolysis of dichlorophosphines over magnesium at 500–600 °C gives the products expected from intramolecular CH insertion of the corresponding phosphinidenes.

Carbenoid Reactions in Rhodium(II)‐Catalyzed Decomposition of Iodonium Ylides

AbstractThe intermediacy of metallocarbenes in decomposition reactions of iodonium ylides with [Rh2(OAc)4] was established by comparison with reactions of the corresponding diazo compounds. The sensitivity of the RhII‐catalyzed intermolecular cyclopropane formation from substituted styrenes and bis(methoxycarbonyl)(phenyliodono)methanide (1a) or dimethyl diazomalonate (1b) is identical. The Hammett plot (with σ+) has a slope of −0.47. Iodonium ylides and diazo compounds afford the same products in [Rh2(OAc)4]‐catalyzed cyclopropane formations, cycloadditions, and intramolecular CH insertions, and exhibit the identical selectivity in intramolecular competitions for cyclopropane formation and insertion. The intramolecular CH insertion of the ylide 20c, when carried out in the presence of a chiral catalyst ([Rh2{(−)‐(S)‐ptpa}4]), results in formation of 21a having an ee of 67%, identical to the ee obtained with the diazo compound 20b.

Rhodium(II) acetate-catalysed decomposition of 2-diazo-3-oxobutanamides derived from L-phenylalanine

In order to developed a practical method for alkylating α-amino acids at the α- or β-carbon atom by intramolecular carbene CH insertion, a series of diazoamides 3a–e was synthesized and subjected to rhodium(II) acetatecatalysed decomposition. The N-benzyl derivative 3a gave mainly the azetidinones 4a and 5a, resulting from a carbene CH insertion into the N-benzyl group. The N-diphenylmethyl derivative 3c yielded, upon treatment with rhodium(II) acetate, the azetidinone 5c, the imine 6c, the cycloheptapyrrolidinone 7c as well as the desired pyrrolidinone 8c (12% yield) the latter resulting from an alkylation of the L-phenylalanine framework at the β-carbon atom.

Rhodium(II)‐Catalyzed Decomposition of β,γ‐Unsaturated Diazo Compounds

AbstractThe RhII‐catalyzed decomposition of β,γ‐unsaturated diazo ketones 1 in the presence of MeOH leads via vinylogous Wolff rearrangement to γ,δ‐unsaturated esters 6 (Schemes 1 and 2). A modest asymmetric induction is achieved when the reaction is carried out with chiral tetrakis(pyrrolidinecarboxylato)‐ or tetrakis(oxazolidinonato)dirhodium(II) complexes. Vinyl and phenyl diazoacetates 11 and 20, respectively, or 1‐diazo‐3‐phenyl‐propan‐2‐one (25), when subjected to the same reaction conditions, react by OH insertion with MeOH (Schemes 3–5). In the absence of MeOH, phenyl diazoacetates 20 and 25 undergo intramolecular CH insertion to 22 and 26, respectively. Intramolecular CH insertion occurs with N‐aryldiazoamides 23 even in the presence of MeOH (Scheme 5).

Alkoxycarbonylnitrenes as selective intramolecular CH-insertion reagents in alicyclic chemistry

Intramolecular CH-insertion of cyclohexyl, cis- and trans-4-t-butylcyclohexyl, and cis- and trans-2-methylcyclohexyl nitrenoformates have been studied. The nitrenes were generated by vapour-phase (spray) pyrolysis or solution thermolysis of the corresponding azides, or by photolysis of tetrachlorothienyl S,N-ylides derived from the azides. The product ratios were principally (and predictably) dependent upon reaction temperatures (and thus conformational equilibria), these varying in the range 10–500°C. 17-Substituted estrone-derived nitrenoformates inserted either into the 12β(from 17β) or 14α(from 17α) CH sites while 17-derivatives with the nitrene on the end of a long inert group abstracted hydrogen from the steroid B-ring.