Enol ethers from diketones

A TMSOTf-initiated cyclization of the dicarbonyl substrate was invoked to explain the reactivity pattern [79]. Selective complexation of the less hindered carbonyl group activates it toward intramolecular nucleophilic attack by the more hindered carbonyl which leads to an oxocarbenium species. Subsequent attack by the enol ether results in addition to the more hindered carbonyl group. The formation of this cyclic intermediate also explains the high stereochemical induction by existing asymmetric centers in the substrates, as demonstrated by Eq. 52, where the stereochemistry at four centers is controlled. A similar reactivity pattern was observed for the bis-silyl enol ethers of / -diketones. The method is also efficient for the synthesis of oxabicyclo[3.3.1] substrates via 1.5-dicarbonyl compounds, as shown in Eq. 53. Rapid entry into more complex polycyclic annulation products is possible starting from cyclic dicarbonyl electrophiles [80]. 

Potassium enolates derived from acylfulvalenes were trapped with TBDMSCl but not TMSCl or diphenylmethylsilyl chloride. Interestingly, TBDMSCl was found to be compatible with CpK anion at —78 °C. TBDMS enol ethers have also been used as /3-acyl anion equivalents. The TBDMS-silyl enol ethers of diketones (eq 7) and /3-keto esters (eq 8) may be prepared by mixing them with TBDMSCl in THF with imidazole. Alcohols may be protected under acidic conditions as their TBDMS ethers by treatment with /3-silyl enol ethers in polar sovents. 

The corresponding enol ether from cyclohexane>l,2 dione is obtained in the same way from the hydrated diketone dimer as obtained from the nitric acid oxidation of cyclo-hexanol this enol ether was used in a Refoimatski reaction... 

As stated previously, 3-monoethyl enol ethers can be prepared from A" -3,17-diketones and A -3,20-diketones by warming with stoichiometric amount or a large excess of ethyl orthoformate at room temperature. With 2,2-dimethoxypropane, the 3-methyl enol ether is the only reaction product even at high temperatures. 

In order to construct the thiepin conjugation, the seven-membered cyclic ketones containing sulfur could be converted to either their enol ethers or enol acetates. The resulting thiepins should have a number of substituents. The first stable 3,5-diacetoxy-4-phenylbenzo[6]thiepin (15) has been obtained by Hofmann et al. from the diketone (14) by acetylation with acetic anhydride in pyridine in good yield 13). By this methodo-... 

It was unfortunate that we did not detect any product derived from a diketone in the reaction of w-dimethoxybenzene with tetrafluoroben-zyne. We therefore carried out a reaction of tetrafluorobenzyne with 1,3,5-trimethoxybenzene. The di-enol ether (80) could not be isolated, and after the removal of unreacted 1,3,5-trimethoxybenzene we isolated the phenolic acid (81) in good yield. This compound is undoubtedly formed by the hydrolysis of (80) followed by a retro-Claisen condensation, and aromatisation as shown below. 

Quite different methods employ carbene intermediates. Spencer and his colleagues generate a carbenoid species from ethyl diazoacetate (CuS04 catalyst) and allow it to attack an enol ether of a 1,3-diketone.102 Scheme... 

Michael reaction. In the presence of (C6H5)3CC104, silyl enol ethers undergo Michael addition to a,p-enones. The adducts can be isolated or rearranged to 1,5-diketones by base. The intermediates cannot be isolated from reactions catalyzed by TiCl4 or CsF. 

Template reactions between malonaldehydes and diamines in the presence of copper(II), nickel(II) or cobalt(II) salts yield neutral macrocyclic complexes (equation 15).99-102 Both aliphatic102 and aromatic101 diamines can be used. In certain cases, non-macrocyclic intermediates can be isolated and subsequently converted into unsymmetrical macrocyclic complexes by reaction with a different diamine (Scheme ll).101 These methods are more versatile and more convenient than an earlier template reaction in which propynal replaces the malonaldehyde (equation 16).103 This latter method can also be used for the non-template synthesis of the macrocyclic ligand in relatively poor yield. A further variation on this reaction type allows the use of an enol ether (vinylogous ester), which provides more flexibility with respect to substituents (equation 17).104 The approach illustrated in equation (15), and Scheme 11 can be extended to include reactions of (3-diketones. The benzodiazepines, which result from reaction between 1,2-diaminobenzenes and (3-diketones, can also serve as precursors in the metal template reaction (Scheme 12).101 105 106 The macrocyclic complex product (46) in this sequence, being unsubstituted on the meso carbon atom, has been shown to undergo an electrochemical oxidative dimerization (equation 18).107... 

Diketones. Silyl enol ethers are C-acylated by acetyl tetrafluoroborate to give 1,3-diketones. Yields are generally higher if the reagent is generated in situ from CH3COF and BF3.2 Examples ... 

At least 19 has the natural polarity of the enone but conjugate addition would lose the alkene so we need to add a leaving group at the site of the plus charge 22. One possibility is an enol ether 23 as these are easily made from 1,3-diketones 24 and a suitable alcohol. 

The alternative to this 0,0-acetal formation is the sequence of addition and El reaction. As a matter of fact, this is familiar from the transformation of alcohols with carbonyl compounds, but only occurs in some (very rare) cases. This is illustrated by Figure 9.31 using acid-catalyzed transformations of ethanol with two /3-diketones as an example. Here, enol ethers, namely 3-ethoxy-2-cyclopentene-l-one and 3-ethoxy-2-cyclohexene-l-one, respectively, are... 

Another analogue of HTI which was used with either ketones or silyl enol ethers was [hydroxy(mesyloxy)iodo]benzene, PhI(OH)OS02Me [25]. A related reagent formed in situ from iodosylbenzene and trimethylsilyl triflate, probably PhI(OSiMe3)OTf, reacted similarly with silyl enol ethers to afford a-ketotriflates (see Table 5.3). /1-Diketones and /1-ketoesters underwent tosyloxylation by HTI the reaction was very effective in substrates with a perfluoroalkyl moiety and gave their hydrates [26] ... 

Fig (13) The adduct (103) prepared from (96) is converted to diketone (104) by Pvmunerer rearrangement. Treatment of (104) with p-TsOH and methanol affords enol ether (105) which on treatment with sodium methoxide in methanol yields the catechol (106) which was converted to ethyl (+)-camosate dimethylether (101) by methylation and hydrogenolysis respectively. 

If the 1,5-diearbonyl compound is required, then an aqueous work-up with either acid or base cleaves the silicon-oxygen bond in the product but the value of silyl enol ethers is that they can undergo synthetically useful reactions other than just hydrolysis. Addition of the silyl enol ether derived from aeetophenone (PhCOMe) to a disubstituted enone promoted by titanium tetrachloride is very rapid and gives the diketone product in good yield even though a quaternary carbon atom is created in the conjugate addition, This is a typical example of this very powerful class of conjugate addition reactions. 

Diketones Prepared from Silyl Enol Ethers and Nitroolefins... 

DIKETONES from silyl enol ethers AND NITROOLEFINS 117... 

SYNTHESIS OF 1,4-DIKETONES FROM SILYL ENOL ETHERS AND NITROOLEFINS 2-(2-OXOPROPYL)CYCLOHEXANONE... 

DIKETONES FROM SILYL ENOL ETHERS AND NITROOLEFINS 119... 

Preussomerin I 697 and ( )-preussomerin G 698 were obtained from 620 with a five- and six-steps sequence in 15% and 12% overall yield, respectively, through modifications of substituents of the dioxocin ring. Thus, attack of lithium methoxide from the less hindered face of the enone 620, followed by protection of the phenolic oxygen as its methyl ether provided the methoxy adduct 692. The ketone 693 was obtained through a benzylic bromination-solvolysis-oxidation protocol, which required only a single purification. The C(2)-C(3) olefin was introduced by selective silylation of the C-l carbonyl of diketone 693 and oxidation of the silyl enol ether with Pd(OAc)2. Enone... 

The direct fluorination with elemental fluorine at — 78 "C of trimethylsilyl enol ethers derived from diketones results in the formation of the corresponding monofluoro diketones 11 in moderate yield. The trimethylsilyl ethers from cyclic diketones undergo smooth fluorination to give the enol forms, c.g. 12, and not the keto forms.Higher yields are generally observed for the analogous reactions of silyl derivatives of esters, carboxylic acids, malonates, dimethyl amides and lactones (Table 4). ... 

Oxidative coupling of silyl enol ethers as a useful synthetic method for carbon-carbon bond formation has been known for a long time. Several oxidants have been successfully applied to synthesize 1,4-diketones from silyl enol ethers, e.g. AgjO [201], Cu(OTf)2 [202], Pb(OAc)4 [203] and iodosobenzene/BFj EtjO [204]. Although some of these reagents above are known to react as one-electron oxidants, the potential involvement of silyl enol ether radical cations in the above reactions has not been studied. Some recent papers, however, have now established the presence of silyl enol ether radical cations in similar C-C bond formation reactions under well-defined one-electron oxidative conditions. For example, C-C bond formation was reported in the photoinduced electron transfer reaction of 2,3-dichIoro-1,4-naphthoquinone (98) with various silyl enol ethers 99 [205], From similar reactions with methoxy alkenes [206,207] it was assumed that, after photoexcitation, an ion radical pair is formed. 

Electron transfer provides a very efficient methodology to the cross-coupling of 1,2-disubstituted and 1-substituted trimethylsilyl enol ethers as demonstrated by Baciocchi and Ruzziconi [208]. Thus, the synthetically important, un-symmetrical 1,4-diketones 107 were formed in good yields from 102 and 104 using Ce(NH. )2(N03)6 (CAN) as one-electron oxidant. 

Formation of the antiaromatic enolate 11 from the low acidity ketone 10 " is evidently unfavourable compared with its acyclic variant 17. Attempts at isolating a stable enol derivative of 10, such as its silyl enol ether, have proved unsuccessful ". Treatment of benzocyclobutanone (10) with LiTMP in THE at —78°C, followed by the addition of trimethylsilyl chloride (MesSiCl), gave the corresponding C-silylated benzocyclobutanone 18 (equation 3) ". The non-aromatic C-lithiated ketone 20 appears to be more preferred than its related 0-lithiated enolate 11. Unlike traditional lithium enolates, this particular lithium enolate reacts in situwilh its parent compound, benzocyclobutanone (10), to give the diketone 19 (equation 3). In comparison, bridgehead enolates have also been shown to be similarly reactive ... 

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