Intramolecular reactions ketone trapping

The [3+2] cycloreversion of bicyclo[ z.3.0]alkan-3-on-2-yl-l-oxonium ylides (m = 3-6) to alkenyloxyketenes is observed and extensively studied <2004JOC1331>. In particular, rhodium(ll)-catalyzed intramolecular reaction of diazomethyl oxepan-2-yl ketone 13 generates a bicyclo[5.3.0]decan-3-one-l-oxonium-2-ylide 14, which undergoes sigmatropic and stereospecific [3+2] cycloreversion to form hept-6-enyloxyketene 15. The latter is trapped by MeOH to form the corresponding ester 16 (Scheme 5). 

This cyclization has obvious applications to the synthesis of steroids and indeed Johnson et al. applied this reaction to a synthesis of dZ-progcsterone. The key step in the synthesis involves the cyclization of (3) to give (4). This reaction was carried out with trifluoroacetic acid as above, but ethylene carbonate was added to the reaction to trap the vinyl cation. After cyclization potassium carbonate was added to hydrolyze the enol complex. In this way (3) was converted into (4) in 71 % yield. The tetracyclic ketone (4) was converted into progesterone (6) by ozonization followed by intramolecular aldol condensation. Nole that (4) is a 5 1 mixture of the 17/7- and 17a-epimeric ketones. The mixture was converted into (6) and then separated by fractional crystallization. 

Under strictly anhydrous conditions, the iminophosphorane intermediate that is formed as a result of the Staudinger reaction can react with aldehydes and ketones in an intermolecular fashion (as in the synthesis of imine 36 described above) or intramolecularly with a variety of carbonyl containing functional groups to afford a host of products. Nitrogen containing ring systems such as cyclic imines (44) represent just one of the many products one can prepare and the reaction is particularly well suited for the facile synthesis of five, six, and seven-membered rings. In addition to aldehydes and ketones, carboxylic acids, esters, thio-esters, and amides can also react in an intramolecular fashion to trap an iminophosphorane to afford a variety of heterocycles. Examples from the current literature are described in Section 2.5.5. 

The following steps are very similar to the formation of a cyclic acetal by the intramolecular reaction of two alcohols with a ketone. One of the alcohols attacks the ketone, which is previously activated by protonation. This produces a hemiacetal, which is converted to a carbocation by protonation of the hydroxy group and water loss. Finally, the carbocation is trapped intramolecularly by the amide nitrogen. 

Amongst miscellaneous intramolecular reactions noted have been intramolecular alkylation of an a,j8-unsaturated ketone at the 7-position [synthesis of ( )-isolongifolene] and an application of intramolecular diyl trapping to the synthesis of linearly fused tricyclopentanoids. The key step in the last example is illustrated from compound (50) it is expected to have utility in syntheses of various natural products. 

Alkyl- and arylmercury(II) halides are used for the ketone formation[402]. When active methylene compounds. such as /f-keto esters or malonates are used instead of alcohols, acylated / -keto esters and malonates 546 are produced, For this reaction, dppf is a good ligand[403]. The intramolecular version of the reaction proceeds by trapping the acylpalladium intermediate with eno-late to give five- and six-membered rings smoothly. Formation of 547 by intramolecular trapping with malonate is an example[404]. 

The irradiation of ortho tolyl ketones affords dienols 413) via an analogous intramolecular H-abstraction. The dienols formed usually tautomerize back to starting material, but they can also be trapped by dienophiles in inter-414a) (4.12) and intramolecular414b) (4.13) Diels-Alder reactions. This latter... 

With the intent of exploiting the intramolecular 1,3-diyl trapping reaction, Little and Muller prepared azo compound 663 and decomposed the substance in refluxing acetonitrile (Scheme LXVI) Triquinane 664, isolated in 85% yield, was then degraded to a saturated ketone which was methylated in the angular position prior to olefination. 

Where the carbon-carbon double bond is a part of an aromatic system, in general, cyclopropanation of diazoketones results in the formation of unstable cyclopropane adducts. For example, Saba140 has shown that in the intramolecular cyclopropanation of diazoketone 57 the norcaradiene ketone 58 can be detected by low-temperature NMR and can be trapped in a Diels Alder reaction with 4-phenyl-l,2,4-triazoline-3,5-dione (equation 69). In addition, Wenkert and Liu have isolated the stable norcaradiene 60 from the rhodium catalysed decomposition of diazoketone 59 (equation 70)105. Cyclopropyl ketones derived from intramolecular cyclopropanation of hetereoaromatic diazoketones are also known and two representative examples are shown in equations 71 and 72106. Rhodium(II) compounds are the most suitable catalysts for the cyclopropanation of aromatic diazoketones. 

Some ketones such as /3-dicarbonyls contain substantial amounts of the enol at equilibrium. For example, acetylacetone in aqueous solutions contains 13% of 4-hydroxypent-3-en-2-one, which is stabilized both by an intramolecular hydrogen bond and the inductive effect of the remaining carbonyl group.17 When bromine is added to such a solution, a portion is initially consumed very rapidly by the enol that is already present at equilibrium. The ketone remaining after consumption of the enol reacts more slowly via rate-determining enolization. The slow consumption of bromine is readily measured by optical absorption. In acidic solutions containing a large excess of the ketone the slow reaction follows a zero-order rate law the rate is independent of bromine concentration, because any enol formed is rapidly trapped by bromine (Scheme 1). In this case, the amount of enol present at equilibrium may be determined as the difference between the amount of bromine added and that determined by extrapolation of the observed rate law to time zero, as is shown schematically in Fig. 2. 

During their studies on the stereochemistry of intramolecular 1,3-diyl trapping reaction as depicted in Scheme 13, Little and collaborators utilized the reductive decarboxylation in preparing the required compound 31.24 The usefulness of Barton decarboxylation was also realized by Braekman and colleagues during their studies on ichthyotoxic sesterterpenoids in providing the needed methyl ketone 32 from the carboxylic acid 33.25 Helmchen has developed an easy route to a stable... 

Intermediate samarium enolates derived from ketones 1522 or 1525 could stereoselectively be trapped with allyl halides, leading to tricycles 1524 and 1526. The intramolecular alkylation by the chloroalkyl terminus of compound 1527 led to tetracyclic compound 1528 with satisfactory efficiency. These cascade reactions selectively generate three continuous stereogenic centers, including a quaternary carbon atom at the 3-position of the dihydroindole moiety, a structural motif of many indole alkaloids. 

Attempts to trap other di-alkyl ketyl radicals from methyl-ethyl, di-ethyl, di-n-propyl and di-isopropyl ketones were unsuccessful. The observed spectrum was not that expected from the ketyl radical but in each case it could be identified as that of a radical formed by a hydrogen abstraction from the parent ketone. The structurally similar radicals, CH3—CH—CO—CHg and CH3—CH—CO—CHa—CHg, were formed from methyl-ethyl and di-ethyl ketone respectively and the radical (0113)2—C—CO—CH—(0113)2 was formed by abstraction of the tertiary hydrogen from di-isopropyl ketone. The reaction of di-n-propyl ketone was somewhat unexpected as the spectrum obtained was typical of that for an allyl radical rather than an alkyl radical. It is possible that the allyl radical was formed by abstraction of a hydrogen adjacent to the carboxyl group in a parent molecule followed by an intramolecular rearrangement. Thus... 

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