Furyl addition, ketone

The behavior of 2-furyl vinyl ketone is similar to that of 2-vinylfuran, in which the monomer is activated in the normal fashion by the primary radical (addition onto the vinylic bond), but the formed polymer chains act as radical traps through their pendant furan ring. Thus at a critical polymer concentration practically all primary radicals are quenched to form stable furyl radicals, and normal initiation cannot take place. This phenomenon of self-retarding is also responsible for the low molecular weight [353]. 

Conjugate addition was almost quantitative for the reaction between di- -butyl zinc or tri-n-butyl aluminum and both methyl isopropenyl ketone and phenyl vinyl ketone. With 2-furyl vinyl ketone an increase in initiator concentration produced crosslinking of the material [353]. 

In the case of methyl vinyl ketone (MVK), similar reactivity is observed. Exposure of MVK (150 mol%) and p-nitrobenzaldehyde to basic hydrogenation conditions provides the corresponding aldol product in good yield, though poor dia-stereoselectivity is observed [24a]. Remarkably, upon use of tris(2-furyl)phos-phine as ligand and Li2C03 as basic additive, the same aldol product is formed with high levels of syn-selectivity [24 e]. Addition of MVK to activated ketones such as l-(3-bromophenyl)propane-l,2-dione is accomplished under similar con-... 

Alkyl halides possessing / -hydrogens are usually poor substrates for carbonylative cross-coupling due to competitive / -hydride elimination/ Allyl chlorides can be used in carbonylative cross-coupling with allylstannanes/ phenyl-, 3-furyl, or vinylstannanes " to afford allylketones in modest to good yields. Divinylketones can be accessed through the reaction of vinylstannanes with vinyl iodides or vinyl triflates, with the latter requiring the addition of LiCl. Synthetic potential of this method has been proved in the formation of macrocyclic ketone jatrophone. In the reaction of vinyl triflates with tetramethyltin or aryltrimethylstannanes the additional activation by ZnCle is required. 

When Grignard reagents were allowed to react with alkyl 2-furyl ketones (371), 1,2-, 1,4- and 1,6-addition products were observed (Scheme 100). The 1,4-addition products (372) were oxidized by air during the work-up procedure to yield (373) and (374) <80ACS(B)435). 

Reactions of diazomethane with various a,(3-unsaturated ketones were described in [27, 28]. For instance, Mustafa and Freifel [27] showed that treatment of chalcones 5 with ethereal diazomethane under normal conditions affected addition to the double bond of the ketone, forming pyrazolines 6 (Scheme 2.2). Alternative directions leading to heterocycles 7 as well as to methylation of the hydroxyl group were not observed. Similar results were described in [28]. On the other hand, Aleksandrova et al. [29] reported the formation of 4-aryl-3-(2-furoyl)-2-pyrazolines 9 when furyl analogues of chalcones 8 react with diazomethane. 

A notable advantage of the HTIB-method is the ready availability of a-tosyloxy derivatives of heteroaryl methyl ketones, thus enabling convenient syntheses of bi-, ter-, and quaterheterocycles. In addition to representatives already cited, examples of such compounds include the (furyl)thiazoles 33 (98SC2371), (pyrazolyl)thiazoles 34 (97JIC940), and the aryl(thienyl)- and bis(thienyl)bithiazoles 35 (01SC3747) shown in Scheme 9. 

Treatment of 2-(l,2-dibromoethenyl)quinoxalines 57 with Na2CS3 affords thieno[2,3- ]quinoxalines 59. Addition of the thiocarbonate to the side chain generates 58. Intramolecular cyclization of 58 with loss of CS2 and NaBr leads to 59 (Scheme 14) <2001J(P1)154>. Azulenothiophenes 61 are prepared from azulene derivatives 60 by the reaction with thioacetamide (Scheme 15) <2002H(58)405>. Similar reactions of furyl ketones 62 afford thieno[3,4-3]furans 63 <1998JHC71>. 

In most aryl ketones the n -> k triplet is similar in energy to the lowest 7t —> 7r triplet and is responsible for the subsequent transformations those ketones with n ->n as the lowest triplet state are relatively unreactive photochemically. Alkyl furyl ketones belong to this last group their photochemical activity is centerd on the furan double bonds rather than on the carbonyl group. This is consistent with the long-lived phosphorescence exhibited by such compounds. 2-Acetylfuran, for example gives with methyl-propene a mixture in which the main isomer has structure 5.14 By contrast, the addition of dimethylbutene to 2-benzoylfuran discloses a return to the... 

Addition of hydrazines to 1,3-difunctional compounds is one of the most common methods employed for the preparation of pyrazoles. For example, several synthesis of pyrazoles have been reported where azide reagents are added to a,P-unsaturated systems. Reactions of trifluoroacetyl enol ether (thiophene) 1 with hydrazines afforded 3-(2-furyl) or 3-(2-thienyl)pyrazoles 2 <05S2744>. A regiospecific one-pot synthesis of trifluoromethyl-substituted heteroaryl pyrazolyl ketones has also been disclosed <05JHC631, 05JHC1055>. 1,3,5-... 

In Section VILA, the 1,2-addition of a hydrogenphosphonic diester or related compound to an a,j5-unsaturated aldehyde or analogous ketone " " was discussed in relation to the synthesis of (l-hydroxyalkyl)phosphonic diesters. The latter are formed under condition of kinetic control whereas 1,4-addition (the so-called Pudovik reaction), which leads to the (2-oxoalkyl)phosphonic diester occur under thermodynamic controP" ". In general, reactions which involve ethylenic aldehydes, or acetylenic aldehydes or ketones, tend to result in adduct formation across the carbonyl group, whilst ethylenic ketones tend to take part in 1,4-additions and afford 3-oxoalkyl phosphonic (or phosphinic) acid systems 550 34,946-949 consistent with Markovnikov predictions. Such statements are a broad oversimplification, however, at least with regard to the formation of the oxoalkyl phosphonates. In practice, the manner of addition depends on experimental circumstances, the nature and even amount of catalyst and other factors For instance, for the additions of dimethyl hydrogenphosphonate to the ketones 561 ( = 1 or 2) and 559 (R" = H, R = 2-furyl, R = Me), carried out by the addition of a trace of saturated MeONa-MeOH solution to a mixture of reactants in diethyl ether, yielded (within 5 min) the respective 1,2-adducts (1-hydroxyalkylphosphonates) in yields of64,69 and 52% ... 

The same researchers also reported a very facile cycloisomerization reaction of allenyl ketones 15 into furans 16 in the presence of gold(III) catalyst (Scheme 8.7) [46, 103-112]. Furthermore, the authors extended this reaction to the cydoisomeriza-tion-addition cascade process of allenyl ketones 15 with enones 17 to produce 2,5-disubstituted furans 18 (Scheme 8.8) [111]. Formation of the latter products was rationalized via two proposed pathways. According to path A, fiiran intermediate 16 undergoes an auration with Au(III)-catalyst to produce the furyl-gold species, which, upon subsequent 1,4-addition to the Michael acceptor 17, generates intermediate 19... 

Two research groups independently extended the electrocyclization system into the stoichiometric formation of pyranylidene complexes (25 and 27), which also proceeds via vinylidene complexes as key intermediates (Scheme 21.10) [16,17], Further reactions of the pyranylidene complexes 25 with a variety of alkenes gave the corresponding naphthalenes 28 in good to high yields. In addition, Miki and others found the catalytic formation of cyclopropanes bearing a furan ring 30 from reactions of ene-yne ketones 29 with a variety of alkenes, where furyl carbene complexes 31 were proposed as key intermediates (Scheme 21.11) [18],... 

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