Cyclic ketene acetals

E)-4-hydroxyenestannanes, with 2 extra C-atoms 44, 850 a-hydroxyketones 43,1 P-hydroxyketones 44,627 hydroxynitriles, synthesis 43, 558 2-hydroxythioethers 43,450 rran5-l,2-iodohydrins 44 922 ketene acetals, cyclic 44, 575... 

In contrast to the acyclic aUyl silyl ketene acetals, cyclic substrates may preferentially rearrange through either the chair or boat transitions states. In 1981 Bartlett and Pizzo reported that treatment of cyclohexenyl propionates under either set of conditions reported by Ireland resulted in the formation of the same major isomer (Scheme 4.17) [20]. They concluded that the -silyl ketene acetal rearranged preferentially via a chair-hke transition state, while the Z-silyl ketene acetal rearranged via a boat-like transition state. These conclusions were recently supported computationally by Houk et al., who reported a 1.0 kcal/mol preference for the boat transition state for the Z-geometry in the analogous OMe ketene acetal and a 1.4 kcal/mol preference for the chair transition state for the -geometry in the OMe ketene acetal [18]. 

The oxidation of the cyclic enol ether 93 in MeOH affords the methyl ester 95 by hydrolysis of the ketene acetal 94 formed initially by regioselective attack of the methoxy group at the anomeric carbon, rather than the a-alkoxy ketone[35]. Similarly, the double bond of the furan part in khellin (96) is converted ino the ester 98 via the ketene acetal 97[l23],... 

Extension of this work by reacting 5-nitropyrimidine with 0,0-ketene acetals and with other cyclic and non-cyclic enamines showed that also with these electron-rich dienophiles the addition is regioselective and gives rise to the formation of 2-mono- or 2,3-disubstituted 5-nitropyridines (Scheme 30). Thus, reaction of 5-nitropyrimidine with the cyclic N,S-ketene acetals 4,5-dihydro-1 -methyl-2-methylthiopyrrole and 4,5,6,7-tetrahydro-1 -methyl-2-methylthioazepine gives in low yields 2,3-dihydro-1-methyl-5-nitropyr-olo[2,3-h]pyridine and the 5,6,7,8-tetrahydro-9-methyl-3-nitropyrido [2,3-Z)]azepine, respectively (89T2693) (Scheme 30). 

A quite different type of titanium catalyst has been used in an inverse electron-demand 1,3-dipolar cycloaddition. Bosnich et al. applied the chiral titanocene-(OTf)2 complex 32 for the 1,3-dipolar cycloaddition between the cyclic nitrone 14a and the ketene acetal 2c (Scheme 6.25). The reaction only proceeded in the presence of the catalyst and a good cis/trans ratio of 8 92 was obtained using catalyst 32, however, only 14% ee was observed for the major isomer [70]. 

Stansbury and Bailey. A review by Colombam on addition-fragmentation processes is also relevant. Monomers used in ring-opening are typically vinyl (e.g. vinylcyclopropane - Scheme 4.20 Section 4.4.2.1) or methylene substituted cyclic compounds (e.g. ketene acetals - Section 4.4.2.2) where addition to the double bond is followed by p-scission. 

Additions of silylated ketene acetals to lactones such as valerolactone in the presence of triphenylmethyl perchlorate in combination with either allyltrimethylsilane 82, trimethylsilyl cyanide 18, or triethylsilane 84b, to afford substituted cyclic ethers in high yields have already been discussed in Section 4.8. Aldehydes or ketones such as cyclohexanone condense in a modified Sakurai-cyclization with the silylated homoallylic alcohol 640 in the presence of TMSOTf 20, via 641, to give unsaturated cyclic spiro ethers 642 and HMDSO 7, whereas the 0,0-diethyllactone acetal 643 gives, with 640, the spiroacetal 644 and ethoxytrimethylsilane 13b [176-181]... 

Nitrobenzene reacts with the O-trimethylsilyl ketene acetal 663 in the presence of tris(dimethylamino)sulfur(trimefhylsilyl)difluoride (Me2N)3S(Me3SiF2) (TASF) to give the O-silylated adduct 1007 a, which can be oxidized in situ, e. g. by bromine, to give the 4-substituted nitrobenzene 1008 in an overall yield of 79% [87] (Scheme 7.28). With less hindered ketene-acetals, however, mixtures of ortho- and para-substituted nitrobenzenes are obtained. Yet, on reaction of 4-fluoronitroben-zene with the cyclic O-trimethylsilyl ketene acetal 1009 the ortho-substitution product 1010 is obtained in 79% yield [87]. 

The stereochemistry of the silyl ketene acetal can be controlled by the conditions of preparation. The base that is usually used for enolate formation is lithium diisopropyl-amide (LDA). If the enolate is prepared in pure THF, the F-enolate is generated and this stereochemistry is maintained in the silyl derivative. The preferential formation of the F-enolate can be explained in terms of a cyclic TS in which the proton is abstracted from the stereoelectronically preferred orientation perpendicular to the carbonyl plane. The carboxy substituent is oriented away from the alkyl groups on the amide base. 

A methylenation of cyclic carbonates such as 6/4-132 using dimethyltitanocene to give a ketene acetal, followed by a subsequent Claisen rearrangement, allowed the synthesis of medium-ring lactones such as 6/4-133 in good yields these are otherwise difficult to obtain. In this transformation, 6/4-133 is formed as a l l-mix-ture of the two atropisomers 6/4-133a and 6/4-133b (Scheme 6/4.33). The substrate... 

Functionalized silacyclobutanes 16 result from photochemical decomposition of [azido-, isocya-nato- and isothiocyanato-bis(tert-butyl)silyl]diazoacetates 15. They undergo a remarkably facile ring-expansion reaction to cyclic O-silyl ketene acetals 17 even at 60°C. 

Other non-traditional preparations of 1,2,3-triazoles have been reported. The rearrangement in dioxane/water of (Z)-arylhydrazones of 5-amino-3-benzoyl-l,2,4-oxadiazole into (2-aryl-5-phenyl-27/-l,2,3-triazol-4-yl)ureas was investigated mechanistically in terms of substituents on different pathways <06JOC5616>. A general and efficient method for the preparation of 2,4-diary 1-1,2,3-triazoles 140 from a-hydroxyacetophenones 139 and arylhydrazines is reported <06SC2461>. 5-Alkylamino-] //-], 2,3-triazoles were obtained by base-mediated cleavage of cycloadducts of azides to cyclic ketene acetals <06S1943>. Oxidation of N-... 

Ketene acetals show a pattern of product formation very similiar to enamines79 Diphenyl-4,4-diacetyl triafulvene is converted to diacetylmethyl cyclopentadiene 529 by S,N-acetals, whilst diphenyl-4,4-dicyano triafulvene undergoes C—C-inser-tion to S,N- and N,N-acetals, e.g. 530/531, resulting in cross-conjugated systems 533/534 by analogy with enamines. Cyclic S,N-acetals 532, however, yield exclusively the bicyclic fulvenes 535 due to additional loss of methyl mercaptan. 

Bromoacetals in basic media can be converted to cyclic ketene acetals (Eq. 51). These -eliminations, previously performed under solid-liquid PTC without solvent and with sonication [70], were further improved by microwave irradiation (Tab. 5.22) [71]. 

Ovchinnikov, V.V., Cherezov, S.V., Cherkasov, R.A., and Pudovik, A.N., Reactivity of cyclic and acyclic hydrophosphoryl compounds in reactions of electrophilic addition to ketene acetals and enamines, Zh. Obshch. Khim., 55,1244, 1985. 

The C,C-coupling reactions of six-membered cyclic nitronates were studied in most detail (274, 478). Here silyl ketene acetal was also used as the test nucleophile. The configurations of most of the starting nitronates and the resulting nitroso acetals were determined by NMR spectroscopy and X-ray diffraction, and also a conformational analysis was performed (see Tables 3.24 and 3.25). 

It should be noted that specially purified individual stereoisomers of six-membered cyclic nitronates were used in coupling with silyl ketene acetal. Hence, the mechanistic model of the C,C-coupling reaction can be discussed on the basis of the configurations of the stereocenters of the starting nitronates of intermediate cations (357) (see Section 3.5.2.1), and the resulting tetrahydro-oxazines (358) (for more details, see below). It should be noted that most of C,C-coupling reactions of six-membered cyclic nitronates with silyl ketene acetal are characterized by a very high diastereoselectivity. 

Partially saturated derivatives can also be prepared through aryl radical cyclization of A-2-halobenzoyl cyclic ketene-iVA-acetals <2005TL3801>. In this event, treatment of ketene-acetal 418 with Bu3SnH afforded good yield of cyclized products 419 and 420, as a mixture of two diastereoisomers, but with a total regioselectivity (Scheme 108). 

Cyclic ketene acetals, which have utility as co-polymers with functional groups capable of cross-linking, etc., have been prepared by the elimination of HX from 2-halomethyl-l,3-dioxolanes. Milder conditions are used under phase-transfer conditions, compared with traditional procedures, which require a strong base and high temperatures. Solid liquid elimination reactions frequently use potassium f-butoxide [27], but acceptable yields have been achieved with potassium hydroxide and without loss of any chiral centres. The added dimension of sonication reduces reaction times and improves the yields [28, 29]. Microwave irradiation has also been used in the synthesis of methyleneacetals and dithioacetals [30] and yields are superior to those obtained with sonofication. 

For this reason, a reinvestigation of the cyclic ketene acetal, 2-methylene-l,3-dioxolane (I), that had been prepared by McElvain and Curry (14) was undertaken. Although McElvain and Beyerstedt (15) reported that benzoyl peroxide had no appreciable effect on diethyl ketene acetal, no such study was reported (14) for the 2-methylene-l,3-dioxolane (I). The synthesis was carried out as follows (6) ... 

In a search for other cyclic acetals that would undergo quantitative ring opening even at room temperature we prepared the seven-membered ketene acetal, 2-methylene-l,3-dioxepane (V), which underwent essentially complete ring opening at room temperature. 

Related work had shown that the nitrogen analogs of the cyclic ketene acetals were readily synthesized and would polymerize with essentially 100% ring opening. For this reason their copolymerization with a variety of monomers was undertaken (6). 

Since the cyclic ketene acetal V will undergo free radical polymerization to produce an ester group, a study was undertaken to see if... 

A wide range of olefins can be cyclopropanated with acceptor-substituted carbene complexes. These include acyclic or cyclic alkenes, styrenes [1015], 1,3-dienes [1002], vinyl iodides [1347,1348], arenes [1349], fullerenes [1350], heteroare-nes, enol ethers or esters [1351-1354], ketene acetals, and A-alkoxycarbonyl-[1355,1356] or A-silyl enamines [1357], Electron-rich alkenes are usually cyclopropanated faster than electron-poor alkenes [626,1015],... 

The PET-oxidative cyclization of unsaturated O-alkyl-O-trimethylsilyl ketene acetals 23 and 27 yields cyclic esters 24, 25, and 28, accompanied by the formation of considerable amounts of non-cyclic esters 26 and 29, respectively [89], The cyclization mode is found to be in accordance with free radical cyclizations of the appropriate esters 26 and 29, performed by heating with organic peroxides [90]. Since organic electrochemistry can be used to oxidize... 

Free Radical Peroxides (monomers cyclic ketene acetals)... 

This indicates the possibility of making addition polymers biodegradable by the introduction of ester linkages in to the backbone. Since the free radical ring-opening polymerization of cyclic ketene acetals, such as 2-methylene-1,3-dioxepane (1, Scheme I), made possible the introduction of ester groups into the backbone of addition polymers, this appeared to be an attractive method for the synthesis of biodegradable addition polymers. 

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