Enolate compounds intramolecular carbonyl derivatives

In intermolecular PET processes, radical ions are formed either as close pairs or as free species from neutral molecules (Sch. 1) [2,6]. Most commonly, carbonyl compounds or related derivatives as for example enol ethers, cyclopropyl ketones, and siloxycyclopropanes are used for intramolecular cyclization reactions. With the exception of cycloadditions the ring-building key step is always an intramolecular bond formation. In PET... 

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

Although a cobalt-catalyzed intermolecular reductive aldol reaction (generation of cobalt enolates by hydrometal-lation of acrylic acid derivatives and subsequent reactions with carbonyl compounds) was first described in 1989, low diastereoselectivity has been problematic.3 6 However, the intramolecular version of this process was found to show high diastereoselectivity (Equation (37)).377,377a 378 A Co(i)-Co(m) catalytic cycle is suggested on the basis of deuterium-labeling studies and the chemistry of Co(ll) complexes (Scheme 81). Cobalt(m) hydride 182, which is... 

The method described here belongs to a group of recently developed procedures comprising the spontaneous intramolecular acylation of active derivatives of metalated p-hydroxy alkanoates. These compounds are available by reactions of carbonyl compounds with ester enolates prepared from S-phenyl alkanethioates6 or phenyl alkanoates,15 as well as by Reformatsky16 or Darzens17 reactions of carbonyl compounds with phenyl a-halo alkanoates. 

Highly stereoselective aldol reactions of lithium ester enolates (LiCR1 R2CC>2R3) with (/0-2-(/ -tolylsulfiny I (cyclohexanone have been attributed to intermediacy of tricoordinate lithium species which involve the enolate and the sulfinyl and carbonyl oxygens of the substrates.43 The O-metallated /<-hydroxyalkanoatcs formed by aldol-type reaction of carbonyl compounds with enolates derived from esters of alkanoic acids undergo spontaneous intramolecular cyclization to /1-lactones if phenyl rather than alkyl esters are used the reaction has also been found to occur with other activated derivatives of carboxylic acids.44... 

The reaction of 1-disilagermirene 22 with ketones is similar to the benzaldehyde case. Thus, reaction with butane-2,3-dione gives a final bicyclic product 41, which also has a norbornane type skeleton (Scheme 15, Figure 13)50. Formation of this compound can be reasonably explained by the initial [2 + 2] cycloaddition of one carbonyl group across the Si=Si bond to form the three- and four-membered ring bicyclic compound 42, followed by the isomerization of disilaoxetane 42 to an enol ether derivative 43. The intramolecular insertion of the second carbonyl group into the endocyclic Si—Ge single bond in 43 completes this reaction sequence to produce the final norbornane 41. In this case, C=0 insertion occurred into the Si—Ge bond rather than the Si—Si bond, which is reasonable due to the weakness of Si—Ge bond. 

Potassium fluoride in a two-phase system was also efficient when 18-crown-6 was present as a phase-transfer catalyst. The desilylation by fluoride produced a 7-0x0 enolate which could be reacted with various electrophiles. Appropriately substituted bicyclo[3.1.0]hexane derivatives 42 and 44 have been used to study this reaction.a,/l-Unsaturated carbonyl compounds gave rise to the formation of Michael adducts, while treatment with triphenylvinylphos-phonium salts gave bicyclo[3.3.0]octenes 46 as the result of a subsequent intramolecular Wittig reaction. 

However, it is clear that vibrational spectroscopy has considerable use beyond the identification of polymorphs and solvates. The infrared spectra obtained on the polymorphs of acetohexamide and selected derivatives has been used to study the tautomerism of the drug compound [127]. It was deduced in this work that Form A existed in the enol form, stabilized by the intramolecular bonding between the O—H and groups that produces a six-membered ring. Form B was characterized by the existence of the keto form, with the urea carbonyl group being intermolecular bonding to a sulfonamide N—H functionality. This behavior can be contrasted with that noted for spironolactone, where no evidence was found for the existence of enolic tautomers in any of the four polymorphs [128]. 

Compounds with this structural motif include P-keto acids (49) and 1,3 dicarboxylic acids (50), which are malonic acid derivatives (as described in Chapter 16, Section 16.5). Heating dicarboxylic 51 (2-ethyl-l,3-propanedioic acid), for example, gives butanoic acid (54) by loss of CO2. Initial intramolecular acid-base reaction of one carboxyl oxygen with the acidic proton of the second carboxyl group (see the arrows shown with 51) gives enol 53 by transition state 52. The carbonyl oxygen of one carboxyl unit must be in close proximity to the acidic proton before they can react, which requires an eclipsed rotamer, as shown in the illustration. 

The Claisen rearrangement [5], the intramolecular reaction of allyl enol ethers 1 to y,<5-unsaturated carbonyl compounds 3, has become a valuable tool for organic synthesis [6]. The sigmatropic process allows a significant alteration of the molecular framework within a single step. The concerted mechanism involves a highly organized transition state 2 that often directs the stereochemical course in the reaction of substituted derivatives and enables the simultaneous formation of two asymmetric centers (Scheme 1). 

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