Enolates intramolecular

Exposure of 270 to the TBSOTf/DIPEA reagent couple once more triggered a cascade of reactions, namely chemoselective thiolactone enolization, intramolecular aldolization, and hydroxyl silylation, which ultimately gave rise to 3,4-trans and 3,4-cis bicyclic thiolactones 271 and 272. Final unmasking of the pseudoanomeric thiol function and terminal hydroxymethyl moiety was performed on the individual precursors 271 and 272 to deliver, as expected, the corresponding thiocarbasugars 273 and 274 in high isolated yields. 

In contrast, lactams such as 2-piperidinone have been a-arylated via the zinc enolate. Intramolecular ketone arylation has been used to construct 4-arylisoqumoline derivatives that have been subsequently converted to the naturally occurring alkaloids cherylline and latifine. ... 

The canonical formulation of the mechanism of the Favorskii rearrangement involves initial deprotonation of the a-carbon to generate an enolate, intramolecular displacement of the leaving group on the a -carbon by the enolate to generate a cyclopropanone, addition of a nucleophile to the cyclopropanone ketone followed by elimination to generate the more stable of two possible carbanions, and protonation to yield the rearranged carboxylic acid derivative. 

We begin with the discussion of intramolecular reactions. An example of a regioselec-tive Dieckmann condensation (J.P. Schaefer, 1967) used an educt with two ester groups, of which only one could form an enolate. Regioselectivity was dictated by the structure of the educt. 

Intramolecular reactions between donor and acceptor centres in fused ring systems provide a general route to bridged polycyclic systems. The cts-decalone mesylate given below contains two d -centres adjacent to the carbonyl function and one a -centre. Treatment of this compound with base leads to reversible enolate formation, and the C-3 carbanion substitutes the mesylate on C-7 (J. Gauthier, 1967 A. Belanger, 1968). 

In an intramolecular aldol condensation of a diketone many products are conceivable, since four different ends can be made. Five- and six-membered rings, however, wUl be formed preferentially. Kinetic or thermodynamic control or different acid-base catalysts may also induce selectivity. In the Lewis acid-catalyzed aldol condensation given below, the more substituted enol is formed preferentially (E.J. Corey, 1963 B, 1965B). 

The silyl enol ethers 209 and 212 are considered to be sources of carbanions. and their transmetallation with Pd(OAc)2 forms the Pd enolate 210. or o.w-tt-allylpalladium, which undergoes the intramolecular alkene insertion and. 1-elimination to give 3-methylcyclopentenone (211) and a bicyclic system 213[199], Five- and six-membered rings can be prepared by this reaction[200]. Use of benzoquinone makes the reaction catalytic. The reaction has been used for syntheses of skeletons of natural products, such as the phyllocladine intermediate 214[201], capnellene[202], the stemodin intermediate 215[203] and hir-sutene [204]. 

In the prostaglandin synthesis shown, silyl enol ether 216, after transmetaJ-lation with Pd(II), undergoes tandem intramolecular and intermolecular alkene insertions to yield 217[205], It should be noted that a different mechanism (palladation of the alkene, rather than palladium enolate formation) has been proposed for this reaction, because the corresponding alkyl enol ethers, instead of the silyl ethers, undergo a similar cyclization[20I],... 

Allenes also react with aryl and alkenyl halides, or triflates, and the 7r-allyl-palladium intermediates are trapped with carbon nucleophiles. The formation of 283 with malonate is an example[186]. The steroid skeleton 287 has been constructed by two-step reactions of allene with the enol trillate 284, followed by trapping with 2-methyl-l,3-cyclopentanedione (285) to give 286[187]. The inter- and intramolecular reactions of dimethyl 2,3-butenylmalonate (288) with iodobenzene afford the 3-cyclopentenedicarboxylate 289 as a main product) 188]. 

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]. 

The intramolecular coupling of organostannanes is applied to macrolide synthesis. In the zearalenone synthesis, no cyclization was observed between arylstannane and alkenyl iodide. However, intramolecular coupling take.s place between the alkenylstannane and aryl iodide in 706. A similar cyclization is possible by the reaction of the alkenylstannane 707 with enol triflate[579]. The coupling was applied to the preparation of the bicyclic 1,3-diene system 708[580]. 

The decarboxylation of allyl /3-keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl fi-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-eIimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

The Pd enolates also undergo intramolecular Michael addition when an enone of suitable size is present in the allyl d-keto ester 744[465]. The main product is the saturated ketone 745, hut the unsaturated ketone 746 and ally-lated product 747 are also obtained as byproducts. The Pd-catalyzed Michael... 

Pd(II)-catalyzed cyclization of the siloxyhexatriene 34 offers a cyclohexe-none annulation method. The Pd enolate 35, formed by transraetallation of the silyl enol ether with Pd(II), is an intermediate which undergoes intramolecular eWo-alkene insertion. Then Pd(II) is regenerated to give 36, and finally cyclohexenone is formed[38]. 

Both enols have their carbon-carbon double bonds conjugated to a carbonyl group and can form an intramolecular hydrogen bond They are of comparable stability... 

A combination of conju gate addition of an enolate anion to an a p unsaturated ketone with subsequent intramolecular aldol condensation... 

Conjugation is more important 1 3 Cyclohexanedione exists mainly in its enol form in spite of the fact that intramolecular hydrogen bonding is impossible due to the distance between the carbonyl group and the enohc —OH group... 

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

The 11,12-carbonate of erythromycin (32) is an older cycHc ester which had greater stabdity and antibiotic activity by diminishing formation of intramolecular enol ether (27) (136,137). A later analogue, the ll-A/-12-0-cychc carbamate of... 

Among numerous examples of the role of the chemical structure in tunneling rotation we select just one, connected with the effect of intramolecular hydrogen bond. In acetyl acetone in stable enol form... 

The efficiency of reduction of benzophenone derivatives is greatly diminished when an ortho alkyl substituent is present because a new photoreaction, intramolecular hydrogen-atom abstraction, then becomes the dominant process. The abstraction takes place from the benzylic position on the adjacent alkyl chain, giving an unstable enol that can revert to the original benzophenone without photoreduction. This process is known as photoenolization Photoenolization can be detected, even though no net transformation of the reactant occurs, by photolysis in deuterated hydroxylic solvents. The proton of the enolic hydroxyl is rapidly exchanged with solvent, so deuterium is introduced at the benzylic position. Deuterium is also introduced if the enol is protonated at the benzylic carbon by solvent ... 

Intramolecular hydrogen-atom abstraction is also an important process for acyclic a,/ -unsaturated ketones. The intermediate diradical then cyclizes to give the enol of a cyclobutyl ketone. Among the by-products of such photolyses are cyclobutanols resulting from alternative modes of cyclization of the diradical intermediate ... 

For unsymmetrieal ketones, two eondensation produets are possible. For example, intramolecular condensation of 2,7-octadione may lead to products which follow from the two possible enolates. 

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