Diazo esters reaction with aldehydes

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]. 

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>. 

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%). ... 

Reaction with enoi ethers. Wenkert and co-workers have examined the copper-catalyzed decomposition of this -diazo compound in the presence of an enol ether of an aldehyde (1) and a ketone (5). In the first case, the expected cyclopropane ester (2) was obtained. This was reduced by lithium aluminum hydride to the diol, which cyclized to the hemiaceta (3) on exposure to acid. Collins oxidation of 3 gave the spiro- 3-methylene-y-lactone 4. 

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. 

The alternative route (Reaction scheme 50) is based on simpler chemicals avoiding the diazo reagent [124]. a-alkylation of isobutyric aldehyde with chloroacetic ester... 

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)]. ... 

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]. 

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). ... 

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. ... 

A simple and efficient method for the preparation of a-diazo- i-hydroxy esters by the condensation of aldehydes with ethyl diazoacetate using chloromethy-lated polystyrene SIL as a heterogeneous catalyst in water was developed [66]. Moderate to excellent yields of the corresponding a-diazo-jl-hydroxy esters were obtained. The catalyst was separated by filtration and reused in five consecutive cycles without any appreciable loss of activity. Later MacMillan s imidazolidinone was noncovalently immobihzed in the pores of siHca gel with the aid of IL 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl) imide (Mac-SILC) (SILC, supported ionic liquid catalyst) [67]. The Mac-SILC as an SIL catalyst was utilized for the enantioselective Diels-Alder reaction of cyclopentadiene and cinnamaldehyde. The Mac-SILC was more active, especially to an electron-rich dienophile, than its homogeneous counterparts, and the reaction could proceed under mild conditions. 

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