0-Keto acetals

Hydroxyl groups are stable to peracids, but oxidation of an allylic alcohol during an attempted epoxidation reaction has been reported." The di-hydroxyacetone side chain is usually protected during the peracid reaction, either by acetylation or by formation of a bismethylenedioxy derivative. To obtain high yields of epoxides it is essential to avoid high reaction temperatures and a strongly acidic medium. The products of epoxidation of enol acetates are especially sensitive to heat or acid and can easily rearrange to keto acetates. 

H2O2, NaHC03, THF. The 10-acetate, which is an a-keto acetate, is cleaved in the presence of the taxol side chain that is prone to hydrolysis with other reagents. ... 

Whereas treatment of ( )-29 with camphanic chloride achieves the selective esterification of the hindered C-9 hydroxyl group, the action of acetic anhydride on (+)- 29 results in the equally selective acetylation of the C-10 hydroxyl group It is not clear to what this discrepancy should be attributed, so we will not offer a rationalization here. This unexpected result is, however, most gratifying because TPAP-NMO oxidation27 of the remaining C-9 hydroxyl furnishes keto acetate 6 (88 % overall yield). You will note that the contiguous keto and acetate functions in 6 are both expressed in the natural product. 

This product is also obtained on alkaline hydrolysis of compounds of the formula RCOCHX2. Similar reactions have been performed on a-keto acetals and y-keto... 

In a similar manner, coccinelline (99) and precoccinelline (100) have been synthesized from 2,6-lutidine (351) (336,450). Thus, treatment of the monolithium derivative (153) of 351 with P-bromopropionaldehyde dimethylacetal gave an acetal, which was converted to the keto acetal (412) by treatment with phenyllithium and acetonitrile. Reaction of 412 with ethylene glycol and p-toluenesulfonic acid followed by reduction with sodium-isoamyl alcohol gave the cw-piperidine (413). Hydrolysis of 413 with 5% HCl gave the tricyclic acetal (414) which was transformed to a separable 1 1 mixture of the ketones (415 and 416) by treatment with pyrrolidine-acetic acid. Reaction of ketone 416 with methyllithium followed by dehydration with thionyl chloride afforded the rather unstable olefin (417) which on catalytic hydrogenation over platinum oxide in methanol gave precoccinelline (100). Oxidation of 100 with m-chloroperbenzoic acid yielded coccinelline (99) (Scheme 52) (336,450). 

In contrast, the regioselectivity of the reaction with acetoacetaldehyde dimethylacetal under the same conditions is poor, resulting in 67% 5-methyl-TP (89JHC1393). In the presence of sodium ethoxide, the reaction leads to 5-methyl-TP exclusively. Here, in the present authors opinion, the regioselection may be controlled by the reaction of the AT anion with the product of base-induced methanol elimination from the keto acetal. 

Mixed acid-base ion-exchange resins.1 Rexyn ion-exchange resins (Fisher Scientific Co.) consist of sulfonic acid beads and quaternary ammonium hydroxide beads. Stowcll and Hauck have used such a resin to convert the keto acetal 1 in one operation to 2-methyl-2-cyclopenlenone-l (2). Two steps are involved acid-catalyzed hydrolysis of the acetal group and hasc-cataly/cd aldol condensation. The first step is reversible, but the second is irreversible. 

Imidoylstannanes may also be cleanly reduced to a-stannylamines in good yields by the use of sodium borohydride in ethanol at ice temperatures (equation 77)324. The same reagent may be used to reduce a,a-dihalo ketimines (equation 78) to /J,/J-dialkoxyamines (which are a-amino keto acetals)325. The products from this reaction are extremely useful intermediates for the synthesis of a wide variety of heterocyclic molecules. 

Biphenyls. A novel route to unsymmetrical biphenyls involves addition of allyltrimethylsilyllithium (1, 8, 273-274) to a keto acetal such as 2 to produce a vinylsilane (3). Treatment of 3 with TiC14 in CH2Cl2-ether at -78->0° results in annelation to 4.6... 

When a-keto acetic acid is treated with one mole of a base, the methylene group which is more acidic reacts with the base. And the reaction with an alkylation reagent gives alkyl products attached to methylene. When this reaction is repeated in the next step, the other hydrogen can also react to a dialkyl product. The two alkylation agents may be the same or different (R, R"). 

The epoxidation of dehydrolinalyl acetate 35 provides the corresponding epoxide 36 (75 %) which can lead to karahanaenone 38, a key odorous component of hop oil621. The epoxide 36 can be converted to the keto acetate 37 (82%) by an electrogenerated acid (EG Acid)-catalyzed rearrangement. Hydrogenation followed by alkaline hydrolysis of 37 gives 6-hydroxy-2,6-dimethyl-7-octen-3-one (86%) and subsequent thermal dehydration at 200 °C affords 38 (Scheme 3-12). 

The keto-acetal 24 was needed for a prostaglandin synthesis.3 Disconnection of the acetal 24a reveals the symmetrical carbon skeleton 25 having 1,4- and 1,5-diCO relationships. There is another 1,4-diCO relationship between the two alcohols. 

Significant progress in the substrate scope of the Pt-cinchona systems has been made in the last 5 years. Besides a-keto acids and esters, a-keto acetals, a-keto ethers, and some trifluoromethyl ketones have been shown to give high ee s. It is now possible to classify ketones concerning their suitability as substrates for the Pt-cinchona catalyst system, as depicted in Figure 18.6. Nevertheless, for the synthetic chemist, the substrate scope is still relatively narrow, and it is not expected that new important substrate classes will be found in the near future. However, the chemoselectivity of this system has not yet been exploited to its full value, and this might be a potential for future synthetically useful applications. 

Cationic cyclization with vinylcyclopropyl silyl ethers.1 These ethers can serve as terminators in a cationic cyclization involving acetals. Thus reaction of the keto acetal 2 with 1 and then with a base and ClSi(CH3)3 provides a vinylcyclopropyl silyl ether 3, which undergoes facile cyclization to an eight-membered ring (4) in the presence of trimethylsilyl triflate. 

The Sceletium alkaloid ( )-A4 (36) has been synthesized as shown in Scheme 5, using previously developed enamine-vinyl ketone ring annulation methodology (see Vol. 7 of these Reports).12 Treatment of the hydrochloride of the 2-pyrroline (32) with the acetal enone (33) gave a mixture of epimeric keto-acetals (34) in 85%... 

Bis(pentafluorophenyl) tin dibromide effects the Mukaiyama aldol reaction of ketene silyl acetal with ketones, but promotes no reaction with acetals under the same conditions. On the other hand, reaction of silyl enol ether derived from acetophenone leads to the opposite outcome, giving acetal aldolate exclusively. This protocol can be applied to a bifunctional substrate (Equation (105)). Keto acetal is exposed to a mixture of different types of enol silyl ethers, in which each nucleophile reacts chemoselectively to give a sole product.271... 

A real example comes in the acylation (Chapter 28) of the enolate from the keto-acetal above and alongside. The molecule is folded downwards and the enolate is essentially planar. Addition presumably occurs entirely from the outside, though the final stereochemistry of the product is controlled thermodynamically because of reversible cnolization of the product whatever the explanation, the black ester group prefers the outside. 

Solid-state structure of bicyclic 1,3,5-trioxocane 4 was studied and supported with molecular mechanics computational data to determine its ring-chain tautomerism with keto acetal 5 (see Section 14.08.2.2.1 <1998J(P1)2353>). 

Enantiomeric monoacetalization of diones. Acid-catalyzed monoacetalization of cA-9-methyldecalin-l,8-dione (2) with (2R,3R)-( -)-l forms a separable mixture of the diastereomeric monoacetals 3 and 4 in the ratio 9 1. The p-keto acetals 3 and 4 undergo... 

Cleavage of a-keto acetals. Nafion-H is recommended as a catalyst for hydrolysis of these acetals to the unstable a-keto aldehydes. The reaction is carried out in two steps (equation I). 

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