Silyl diazo ketones

Diazocarbonyl compounds can also be prepared by C-acylation of diazoalkanes with polystyrene-bound acyl halides (Entry 6, Table 10.19). As an alternative to diazomethane, the more stable a-(trimethylsilyl)diazomethane may be used, which is sufficiently nucleophilic to react with acyl halides. On heating, the resulting a-(trimethyl-silyl)diazo ketones undergo Wolff rearrangement to yield ketenes, and have also been used as starting materials for the preparation of oxazoles [368]. 

Aryl diazo ketone conversion into the silylated diazo ketone in a one-pot procedure using a silyl triflate and then Wolff rearrangement catalyzed by triflic acid generates the stable aryl(trialkylsilyl)ketene (Scheme 7.45). 

Thus detrifluoroacetylative diazo transfer furnished the diazo ketone in 80% yield, which was converted to the silyl diazo ketone in 75% yield by the method of Maas. The key photolysis step was effected by irradiating a degassed 0.1M solution of the silyl diazo ketone in hexane in a Vycor tube using a low-pressure mercury lamp (300 nm) for 2 h. Concenhation and chromatographic purification furnished the desired (silyl)vinylketene in 73% yield. ... 

Reactions of trimethylsilyl enol ethers with diazo ketones give cyclopropanes contaminated by ring opened compounds 60,61). Use of the more stable tert-BuMe2Si-derivatives or of Rh2 (0Ac)4 as a catalyst might eventually improve the situation. O-Silylated ketene acetals and O.S-ketene acetals, respectively, did not provide products with cyclopropane structure 61 ... 

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>. 

Table 15. l-Acyl-2-oxycyclopropanes from Diazo Ketones and Enol Ethers or Enol Acetates or O-Silyl Enols... 

A general route to exo-precursors of type 127 starts with copper-catalyzed carbenoid cyclization of diazo compounds. For example, vinylcyclopropane 130, prepared by heating diazo ketone 129 in the presence of copper bronze, is converted into the silyl enol ether to give the substrate for Cope rearrangement888. 

Dicarbonyl compounds are formed from the reaction of silyl enol ethers with methyl vinyl ketones in the presence of BF3 OEt2 and an alcohol (eq 9). a-Methoxy ketones are formed from a-diazo ketones with BF3-OEt2 and methanol, or directly from silyl enol ethers using iodobenzene/BF3-OEt2 in methanol. ... 

Preparation of Diazo Ketones. Diazo(trimethylsilyl)methyl-lithium reacts with lactones to give the product of ring opening, the diazo alcohol, although the silyl group is lost during workup (eq 6). The diazo alcohol can subsequently be cyclized to the corresponding oxepane by treatment with dirhodium(II) tetraacetate. 

Diazaphospholes are known to undergo facile 1,3-dipolar cycloaddditions with a variety of dipoles [2, 4, 7, 98], During recent years, some interesting [2+3] cycloaddition reactions have been reported. 2-Acyl-[l,2,3]diazaphospholes 6 were reported to undergo [2+3] cycloaddition with diazocumulene 92, the minor equilibrium isomer of a-diazo-a-silyl ketones 91, to form a bicyclic cycloadduct 93 (Scheme 29). Thermolysis of the cycloadduct results in the formation of tricyclic phosphorus heterocycle 94, which can be explained due to the possibility of two parallel reactions of cycloadduct. On the one hand, extrusion of molecular nitrogen from 93... 

This silyl hydrazone formation-oxidation sequence was originally developed as a practical alternative to the synthesis and oxidation of unsubstituted hydrazones by Myers and Furrow [31]. The formation of hydrazones directly from hydrazine and ketones is invariably complicated by azine formation. In contrast, silyl hydrazones can be formed cleanly from /V,/V -bis(7< rt-butyldimethylsilyl)hydrazine and aldehydes and ketones with nearly complete exclusion of azine formation. The resulting silylhydrazones undergo many of the reactions of conventional hydrazones (Wolff-Kishner reduction, oxidation to diazo intermediate, formation of geminal and vinyl iodides) with equal or greater efficiency. It is also noteworthy that application of hydrazine in this setting may also have led to cleavage of the acetate substituents. 

Our retrosynthesis of (—)-kinamycin F (6) is shown in Scheme 3.20 [45]. It was envisioned that (—)-kinamycin F (6) could be prepared from the protected diazofluorene 114 by conversion of the ketone function of 114 to a trans-], 2-diol, followed by deprotection of the acetonide and methoxymethyl ether protecting groups. The diazofluorene 114 was envisioned to arise from diazo transfer to the hydroxyfulvene 115. The cyclopentadiene substructure of 115 was deconstructed by a two-step annulation sequence, to provide the bromoquinone 116 and the p-trimethylsilylmethyl unsaturated ketone 117. The latter two intermediates were prepared from juglone (118) and the silyl ether 119, respectively. 

Silyl-substituted diazoketones 29 cycloadd with aryl isocyanates to form 1,2,3-triazoles 194 (252) (Scheme 8.44). This reaction, which resembles the formation of 5-hydroxy-l,2,3-triazoles 190 in Scheme 8.43, has no analogy with other diazocarbonyl compounds. The beneficial effect of the silyl group in 29 can be seen from the fact that related diazomethyl-ketones do not react with phenyl isocyanate at 70 °C (252). Although the exact mechanistic details are unknown, one can speculate that the 2-siloxy-1-diazo-1-alkene isomer 30 [rather than 29 (see Section 8.1)] is involved in the cycloaddition step. With acyl isocyanates, diazoketones 29 cycloadd to give 5-acylamino-l,2,3-thiadiazoles 195 by addition across the C=S bond (252), in analogy with the behavior of diazomethyl-ketones and diazoacetates (5). 

Substitution of the acetate group at the C-3 position of the /3-sultam 105 can occur by reaction with silyl enol ethers in the presence of zinc iodide or zinc chloride. When the diazo compound is used, after desilylation with tetrabutyl-ammonium fluoride (TBAF), photochemical cyclization gives the bicyclic /3-sultam 106 as a mixture of two cis/ fra -diastereoisomers. When silyl enol ethers derived from cyclic ketones are used, the substitution product is stabilized by a retro-Michael-type reaction leading to open-chained sulfonamides 107 (Scheme 31) <1997LA1261>. 

Boron enolatcs 6, which arc also used as activated derivatives of carbonyl sub-strates, " can be similarly obtained from silyl enolethers 4, - or from diazo-carbonyl compounds 7 (Fig. 7), as well as from a, P-unsaturated ketones. - ... 

The Mukaiyama-Michael addition of silyl enolates to a, -unsaturated thioesters is promoted by an SbCl5-Sn(OTf)2 binary catalyst to afford d-keto thioesters with high anti selectivity (Scheme 14.23) [60]. The successive treatment of lactones with a ketene silyl acetal and silyl nucleophiles in the presence of an SbCl5-Me3SiCl-Snl2 ternary catalyst yields a-mono- and a/ -disubstituted cyclic ethers (Scheme 14.24) [61]. SbFs promotes the condensation of a,y5-unsaturated aldehydes and ketones with a-diazo-carbonyl compounds to give cyclopropane derivatives in high isomeric purity [62]. 

The total synthesis of the isoprostane ( )-8-epi-PGF2a ether is accomplished via cyclization of diazo keto silyl derivative 200. Aldol condensation of diazoketone 198 with decadienal (199) in the presence of KHMDS followed by addition of LiBr provides an intermediate P-hydroxy adduct 201 which is not isolated but is immediately silylated to give silyl derivative 200.86 Diazo hydroxy ketones 201 and 203 are silylated with ClSi(Et)3 and chloro dimethyl-Mributylsilane to afford silylated diazoketones 202 and 204, respectively.86... 

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