Diazocarbonyl compounds insertion

Diazoacetic esters, reactions with alkenes, alkynes, heterocyclic and aromatic compounds, 18, 3 26, 2 a-Diazocarbonyl compounds, insertion and addition reactions, 26, 2 Diazomethane ... 

In the same area, good levels of enantioselectivity have been achieved in intramolecular C H insertion reactions of a-diazocarbonyl compounds... 

Based on a detailed investigation, it was concluded that the exceptional ability of the molybdenum compounds to promote cyclopropanation of electron-poor alkenes is not caused by intermediate nucleophilic metal carbenes, as one might assume at first glance. Rather, they seem to interfere with the reaction sequence of the uncatalyzed formation of 2-pyrazolines (Scheme 18) by preventing the 1-pyrazoline - 2-pyrazoline tautomerization from occurring. Thereby, the 1-pyrazoline has the opportunity to decompose purely thermally to cyclopropanes and formal vinylic C—H insertion products. This assumption is supported by the following facts a) Neither Mo(CO)6 nor Mo2(OAc)4 influence the rate of [3 + 2] cycloaddition of the diazocarbonyl compound to the alkene. b) Decomposition of ethyl diazoacetate is only weakly accelerated by the molybdenum compounds, c) The latter do not affect the decomposition rate of and product distribution from independently synthesized, representative 1-pyrazolines, and 2-pyrazolines are not at all decomposed in their presence at the given reaction temperature. 

Synthesis of a-alkoxyketones from a-diazocarbonyl compounds and alcohols under the influence of copper or rhodium catalysts is well established as an alternative to the Lewis or proton acid catalyzed variant of this synthetic transformation. The sole recent contribution to the aspect of general reactivity deals with the competition between O/H insertion and cyclopropanation of unsaturated alcohols 162). The results... 

Transition metal-catalyzed reactions of ct-diazocarbonyl compounds proceed via electrophilic Fischer-type carbene complexes. Consequently, when cr-diazoketone 341 was treated, at room temperature, with catalytic amounts of [ RhiOAcbh, it gave the formation of a single NH insertion product, which was assigned to the enol stmcture 342. At room temperature, in both solid state and in solution, 342 tautomerizes to give the expected 1-oxoperhydropyr-rolo[l,2-c]oxazole derivative 343 (Scheme 50) <1997TA2001>. 

Table 4.4. Intramolecular 1,4-C-H insertions of electrophilic carbene complexes generated from diazocarbonyl compounds.

Ylide formation, and hence X-H bond insertion, generally proceeds faster than C-H bond insertion or cyclopropanation [1176], 1,2-C-H insertion can, however, compete efficiently with X-H bond insertion [1177]. One problem occasionally encountered in transition metal-catalyzed X-H bond insertion is the deactivation of the (electrophilic) catalyst L M by the substrate RXH. The formation of the intermediate carbene complex requires nucleophilic addition of a carbene precursor (e.g. a diazocarbonyl compound) to the complex Lj,M. Other nucleophiles present in the reaction mixture can compete efficiently with the carbene precursor, or even lead to stable, catalytically inactive adducts L M-XR. For this reason carbene X-H bond insertion with substrates which might form a stable complex with the catalyst (e.g. amines, imidazole derivatives, thiols) often require larger amounts of catalyst and high reaction temperatures. 

Table 4.19. C-O Bond insertion reactions of acceptor-substituted carbene eomplexes generated from diazocarbonyl compounds.

A density functional study has been made of the competition between Wolff rearrangement and [1,2]-H shift in /S-oxy-a-diazocarbonyl compounds. Silver-catalysed decomposition of a-diazoketones (88 n = 0), derived from A-tosyl a-amino acids in methanol, gave rise to mixtures of products of Wolff rearrangement (89) and direct insertion of the carbene into the NH bond (90). The -amino acid derived species (88 n = 1) gave rise to products of Wolff rearrangement. 

For a review of the intramolecular insertions of carbenes or carbenoids generated from diazocarbonyl compounds, sec Burke Grieco Org. React. 1979,26, 361-475. 

Peptide-Based Oxazoles by Rhodium-Mediated Carbenoid Insertion of Diazocarbonyl Compounds into an Amide N-H Bond Followed by... 

The intramolecular C-H insertion of a-diazocarbonyl compounds proceeds with excellent regioselectivity affording chroman-4-ones and with good enantioselectivity when Rh (II) carboxylates are used as the catalyst (95JCS(P1)1373). 

Metal-catalyzed insertion reactions of a-diazocarbonyl compounds... 

Only insertion into the S-C(2) bond of 4-amino-2,5-dihydrothiophene-3-carbonitriles is observed on reaction with a-diazocarbonyl compounds in the presence of rhodium(ll) acetate. The ring expansion is regioselective and leads to the 4-cyano-3,6-dihydro-277-thiopyrans there is no evidence for the 5-cyano isomer (Scheme 152) <2000JPR494, 2001M721>. The reaction follows a different sequence when applied to 2-amino-4,5-dihydrothiophene-3-carboni-triles. The initial product is a 1,4-oxathiocine 447 which rearranges thermally to a 3,4-dihydro-2//-thiopyran (Scheme 153) <1996LA725>. 

When the carbene and amine centers are separated by a three-carbon chain, carbene insertion into the N—H bond results in the formation of pyrrolidine derivatives. Both a-diazocarbonyl compounds 58 and a-diazo jS-keto ester 59 give, under the action of Rh2(OAc)4, products of carbenoid insertion into the amide N — H bonds in near quantitative yields. 

The use of diazocarbonyl compounds in the synthesis of O-bridged systems is the approach of choice. There are a few main synthetic strategies of bridged framework building based on this approach tandem cyclization with carbonyl ylide formation/cycloaddition, tandem cyclization with 0x0-nium ylide formation/sigmatropic shift, intramolecular cyclopropanation, and cyclization with single bond insertion. 

Diazoalkanes 1 form a versatile class of functionalized organic compounds [1]. Their undisputed significance in organic synthesis is manifested in a number of organometallic and other metal-induced reactions [2], some of which have entered catalytic applications. Cyclopropanation is one of them (cf. Section 3.1.7) but intramolecular carbon-hydrogen insertion appears of much potential in synthesis, too. This type of reaction relates to the easily available, normally nonexplosive a-diazocarbonyl compounds (a-diazoketones. Structure 2). 

Allyldiethylamine behaves similarly, but the yields are low since neither the starting amine nor the products are stable to the reaction conditions. For the efficiency of the cyclopropanation of the allylic systems under discussion, a comparison can be made between the triplet-sensitized photochemical reaction and the process carried out in the presence of copper or rhodium catalysts whereas with allyl halides and allyl ethers, the transition metal catalyzed reaction often produces higher yields (especially if tetraacetatodirhodium is used), the photochemical variant is the method of choice for allyl sulfides. The catalysts react with allyl sulfides (and with allyl selenides and allylamines, for that matter) exclusively via the ylide pathway (see Section 1.2.1.2.4.2.6.3.3. and Houben-Weyl, Vol. E19b, pll30). It should also be noted that the purely thermal decomposition of dimethyl diazomalonate in allyl sulfides produces no cyclopropane, but only the ylide-derived product in high yield.Very few cyclopropanes have been synthesized by photolysis of other diazocarbonyl compounds than a-diazo esters and a-diazo ketones, although this should not be impossible in several cases (e.g. a-diazo aldehydes, a-diazocarboxamides). Irradiation of a-diazo-a-(4-nitrophenyl)acetic acid in a mixture of 2-methylbut-2-ene and methanol gave mainly l-(4-nitrophenyl)-2,2,3-trimethylcyclo-propane-1-carboxylic acid (19, 71%) in addition to some O-H insertion product (10%). ... 

Carbenoid addition of diazocarbonyl compounds to pyrrole, A -alkylpyrroles, indole, N-alkylindoles, imidazole, and benzimidazole does not result in cyclopropanation, but leads to the formal products of carbene insertion into a heterocyclic C-H bond (see Houben-Weyl, Vol.E19b, ppll58 and 1334). However, Af-acylpyrroles, and Af-acylindoles - " have successfully been converted into 2-azabicyclo[3.1.0]hex-3-ene-exo-6-carboxylates and alkyl-1,la,2,6b-tetrahydrocyclopropa[ ]indole-exo-l-carboxylate, respectively (for an experimental procedure, see Houben-Weyl, Vol.E19b, pll60). 

In certain cases, the metal-carbene complex derived from an unsaturated diazocarbonyl compound can be trapped intramolecularly in reactions other than cyclopropanation, e.g. C-H insertion and ylide formation by interaction with a heteroatom with a lone pair. Since the chemoselectivity is influenced by the electrophilicity of the metal-carbene complex, it may be controlled in favorable cases by the catalyst metal and its ligands or by the second substituent at the carbenoid carbon atom. 

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