Keto aldehydes formation

Petrow described the formation of 3-iminoketones from 3-keto-aldehydes and aniline. Cyclization in the presence of aniline hydrochloride and ZnCh smoothly provides the desired quinoline 26. Bis-imine 24 is the proposed intermediate that undergoes cyclization. The aldimine is more reactive than the ketimine toward cyclization thus, cyclization on the aldimine occurs. When the bis-imine is not formed, partial aniline migration can occur which results in mixtures of cyclized products. 

We have previously discussed that keto-aldehydes react with anilines first at the aldehyde carbon to form the aldimine. Subsequent condensation with another aniline formed a bis-imine or enamino-imine. The aniline of the ketimine normally cyclizes on the aldimine (24 —> 26). Conversely, cyclization of the aldimine could be forced with minimal aniline migration to the ketimine using PPA (30 —> 31). The use of unsymmetrical ketones has not been thoroughly explored a few examples are cited below. One-pot enamine formation and cyclization occurred when aniline 48 was reacted with dione 49 in the presence of catalytic p-TsOH and heat. Imine formation occurred at the less-hindered ketone, and cyclization with attack on the reactive carbonyl was preferred. ... 

Second step. The elements of CH4O3 are eliminated. The most likely by-products are H20 and HCOOH. Make None. Break C4-C5, C6-O8, 010-011. The base can deprotonate the OH on C5, and the lone pair on O can then push down to form a n bond with C5, causing the C4-C5 bond to break. The electrons keep getting pushed around until they end up on O again and the 0-0 bond is broken, providing the driving force for the step. A keto-aldehyde and formate anion are obtained. Now C7 (deprotonated) is nucleophilic and C6 is electrophilic, so an aldol reaction followed by dehydration gives the observed product. 

Acetylation of epoxy diol 49 followed by Dess-Martin periodinane [DMP] oxidation afforded epoxyketone 53 in 90% overall yield. Deacetylation of 53 led to the formation of epoxy lactol 54, and PCC oxidation successfully oxidized 54 to give the desired keto-aldehyde 55 in 71% yield. Attempts to go from 49 to 55 directly via a double Swem oxidation were not successful. 

The keto-aldehyde can be made by a simple Claisen ester condensation (Chapter 28) using the enolate of the methyl ketone with ethyl formate (HCC Et) as the electrophile. It actually exists as a stable enol, like so many 1,3-dicarbonyl compounds (Chapter 21). 

In conclusion, the use of zeolites as catalysts in the isomerization of isophorone oxide 23, yields up to 86% keto aldehyde 24. The formation of 26 by... 

The 1,5-diketone formation by the Michael addition of allylsilane (48) to a, -unsaturated ketones was applied to the synthesis of (+)-nootkatone. Reaction of the keto group of keto aldehyde (58) with allyl Orignard reagent and dehydration gave the diene aldehyde (59). The selective oxidation of the terminal double bond afforded the 1,5-dica nyl compound (60), which is not stable and converted directly to pyridines and phenols (Scheme 18). ... 

Acylation of ketones having reactive methylene groups by higher esters has been shown to be an excellent method for preparing /3-diketones (method 203). If the acylating ester is an alkyl formate, then a keto aldehyde is formed (50-80%). The formylation is simply brought about by adding sodium metal to a mixture of the ketone and ester in anhydrous ether. Oftentimes, the product is isolated as the sodium salt of the hydroxymethylene form. The point of attack is unpredictable in unsymmetrical ketones, CHjCOCHjR. ... 

It has been suggested" that the formation of the keto-aldehyde (137) in relatively high yield from the sensitized photo-oxidation of thujopsene (138) can best be explained in terms of a dioxetan intermediate (139), similar examples of which have recently been found in singlet oxygen addition to electron-rich double bonds. An extensive analysis of the products of acid-catalysed rearrangement of thujopsene (138) has been carried out." Under different acid conditions ten products have been isolated and identified these include the known compounds, chami-grene (140), cuparene (141), and widdrol (142 R = H) together with the previously unknown compounds (142 R = Et) and (143)—(148). The authors have put forward a mechanistic scheme to explain the formation of all these compounds based on interconversions of cyclopropylcarbinyl and homoallyl cations. 

Indirect electrooxidation of cyclic aziridines using NaCl or NaBr as a redox catalyst results in C(l)-C(2) bond cleavage under formation of the corresponding keto nitriles. This reaction is explained by the intermediate generation of an azaallenyl cation, which is hydrated to the o -hydroxyimine. Further oxidation by Cl" then would lead to the open-chain keto A-chloroimine, which by HCl elimination forms the keto nitrile, while its hydrolysis leads to the keto aldehyde as a side product [32] ... 

Initially, application of this method to the formation of 5-membered carbocycles was reported by Sinay et al. [222]. In their case, a dialdehyde was used as the substrate, and cyclization occurred with a comparable overall yield of carbocyclic cw-diols but with much lower diastere-oselectivity. Later, ladonisi et al. reported the results of the application using keto-aldehydes as the substrates [223]. Compared to Sinay s results, cyclization of the keto-aldehydes occurred with a relatively high stereoselectivity, and it should be suggested that, in particular, electrostatic interactions play an important role in the stereocontrol of this reaction. 

Uenishi, J., Masuda, S., Wakabayashi, S. Intramolecular Sm and Sm promoted reaction of y-oxy-5-keto aldehyde stereocontrolled formation of pinacol and lactone. Tetrahedron Lett. 1991, 32, 5097-5100. 

Trehazolamine. Chiara has described a synthesis of trehazolamine, the aglycon of trehazolin, a powerful inhibitor of trehalase, wherein a pinacol cyclization provided the necessary cyclopentane framework (Eq. 3.2) [17]. Thus, treatment of the tetrabenzyl-protected keto aldehyde, derived from D-glucose, with Sml2 furnished the two cis diols exclusively as a 1 1 mixture of isomers in excellent yield (>90%) [18]. Previous studies of five-membered ring formation mediated by SmE have also reported good cis/trans selectivity, presumably due to the intervention of a samarium chelate. 

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