Diazo esters with aldehydes

An ab initio study of the Wolff rearrangement of 1,2-ketocarbene, C6H4O, in the gas phase has been undertaken, and a quantum-chemical investigation of solvent effects on the competition between the Wolff transposition (307) (308) and 1,2-H-shift process (307) (309) in /3-hydroxyketocarbenes has been carried out. It has been found that in the reaction of a-diazo esters with aldehydes in the presence of a stoichiometric amount of trimethylsilyl trifluoromethanesulfonate, 1,2-nucleophilic rearrangement of the substituent derived from the aldehyde is favoured, resulting in the... 

Aldehydes are efficiently converted to /3-diketo esters in 50-90 % yield by addition of ethyl diazoacetate in the presence of SnCl2 (Eq. 5). Although the reaction can be effected by a variety of Lewis acids, SnCl2, BF3, and GeCl2 are the most effective [14]. 1,3-Diketones can be prepared in 42-90 % yield by SnCl2-catalyzed reaction of a-diazo ketones with aldehydes (Eq. 6) [15]. 

The reaction has also been applied to compounds with other leaving groups. Diazo ketones, diazo esters, diazo nitriles, and diazo aldehydes react with trialkylboranes in a similar manner, for example. 

Diazocycloalkanones with five- to twelve-membered rings can be synthesized by the present procedure in good yields (Table I).4 Diazo transfer with deformylation can also be used for the preparation of bicyclic a-diazo ketones.10,11 A related procedure involving reaction of the sodium salt of an a-(hydroxy methylene)-ketone with p-toluenesulfonyl azide in ethanol has been applied to the synthesis of diazoalkyl ketones, a-diazo aldehydes, and a-diazo carboxylic esters.12... 

Further studies on a-diazo ketones with a second more remote carbonyl group have appeared and formation of a carbonyl ylide and its addition to an added aldehyde yields bicyclic dioxolanes 199 (Scheme 19) <2004TL6485, 2005ARK(xi)146>. A rearrangement is clearly involved in the more complex reaction of a silyl diazo ester to give a dioxolan-4-one (Equation 66) <20020L4631>. 

Reagents formed in situ by reaction of r-BUjZnI with organic halides add to carbonyl compounds, such mixed zincates do not transfer their f-butyl group. a-Diazo- 3-hydroxy esters are formed by treatment of diazoacetic esters with Et Zn and aldehydes at low temperature. Allylzinc species derived from allylic esters add to carbonyl compounds to give a- or y-adducts according to the nature of the latter. ... 

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%). ... 

This method was used in the stereoselective synthesis of cis- and /ran -hemicaronic aldehydes 9 which were prepared in high enantiomeric purity starting from optically active sorbic aldehyde diene tricarbonyliron complex 6 via Wittig olefination, diazo ester cyclopropanation (copper powder), and further conversion with release of the cyclopropane from the complex and ozonolysis. ... 

Treatment of aldehydes with two equivalents of a-bromoketones and Bu Sb produces a,//-unsaturated ketones and debrominated ketones [109], whereas the b.-cal-aly/ed reaction with equimolar amounts of the ketones and It jSb gives -hydroxy-ketones (Scheme 14.45) [110]. The olefination of carbonyl compounds with diazo esters is mediated by BujSb under copper catalysis (Scheme 14.46) [111]. 

Insertions into Aldehyde C-H Bonds. The a-diazo ketones (and esters) derived from diazomethane and an acid chloride (or chloroformate) will also insert into the C-H bond of aldehydes to give 1,3-dicarbonyl derivatives. The reaction is catalyzed by SnCL, but some simple Lewis acids, such as BF3 etherate, also work. The reaction works well for ahphatic aldehydes, but gives variable results with aromatic aldehydes, at times giving none of the desired diketone (eq 32). StericaUy hindered aldehydes will also participate in this reaction, as illustratedin eq 33 with the reaction of ethyl a-diazoacetate and pivaldehyde. In a related reaction, a-diazo phosphonates and sulfonates will react with aldehydes in the presence of SnCL to give the corresponding -keto phosphonates and sulfonates. This reaction is a practical alternative to the Arbuzov reaction for the synthesis of these species. 

The hydroxide-catalyzed addition of a-acyldiazomethane derivatives, while quite facile with aldehydes to produce stable aldol adducts, is poor with aliphatic ketones. However, the lithium or magnesium anion (26) adds smoothly to produce the corresponding aldol adducts (27) in good yield (Scheme 8). On treatment with acid, thermolysis or metal catalysts, these adducts lose nitrogen and rearrange to the 3-keto esters (28) and (29). The analogous reaction with a-diazo ketones has also been carried out however, with bulkier substituents, the retro-aldol reaction competes with rearrangement. 

Aldehydes react with the lithio-derivatives of a-diazo-esters to give /3-hydr-oxy>a-diazo-esters, which in turn undergo rhodium(ii)-catalysed decomposition to give /3-keto-esters./3-Keto-amides are obtained in moderate to high yield from the acylation of amide enolates with mixed anhydrides. In a general reaction, orthoformates react with acidic methines to give /3-keto-aldehydes, isolated as their dialkyl acetals [equation (16)]. ... 

There are two important rhodium-catalyzed transformations that are broadly used in domino processes as the primary step. The first route is the formation of keto carbenoids by treatment of diazo keto compounds with Rh11 salts. This is then followed by the generation of a 1,3-dipole by an intramolecular cyclization of the keto carbenoid onto an oxygen atom of a neighboring keto group and an inter- or intramolecular 1,3-dipolar cycloaddition. A noteworthy point here is that the insertion can also take place onto carbonyl groups of aldehydes, esters, and amides. Moreover, cycloadditions of Rh-carbenes and ring chain isomerizations will also be discussed in this section. 

Acceptor-monosubstituted diazomethanes can be further converted into other types of diazo compound. C-Acylation of diazoacetic esters generally requires very reactive acylating agents, such as acid chlorides [969,970] or bromides [971]. C-Alkylations of acyldiazomethanes are best accomplished by metallation followed by treatment with a carbon electrophile [972-977], C-alkylation can also occur without any base if sufficiently electrophilic aldehydes or ketones are used [973,978 -982] or if the alkylation proceeds intramolecularly [983]. 

Seyferth s diazomethane phosphonic acid dimethyl ester, which enables the aldehyde —> alkyne elongation shown in Figure 14.30, is unstable. This is why Bestmann replaced it by a less sensitive synthetic equivalent, namely diazo acetone phosphonic acid dimethyl ester (Formula C in Figure 14.31), since with potassium methoxide—which is proportionately present in a solution/suspension of solid potassium carbonate in dry methanol—the dia-... 

This homologation reaction most likely proceeds via nucleophilic addition of the diazo compound to the Lewis acid complexed carbonyl, followed by 1,2-alkyl migration with concomitant loss of N2. Application of this reaction to an aldehyde (168) gives, via 1,2-hydride shift, the corresponding P-keto ester (169 equation 70). ... 

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