5-alkyl dioxolanes

Deng and co-workers have also applied the cinchona derivatives to the kinetic resolution of protected a-amino acid N-carboxyanhydrides 51 [48]. A variety of alkyl and aryl-substituted amino acids may be prepared with high se-lectivities (krei=23-170, see Scheme 10). Hydrolysis of the starting material, in the presence of the product and catalyst, followed by extractive workup allows for recovery of ester, carboxylic acid, and catalyst. The catalyst may be recycled with little effect on selectivity (run 1, krei=114 run 2, krei=104). The reaction exhibits first-order dependence on methanol and catalyst and a kinetic isotope effect (A MeOH/ MeOD=l-3). The authors postulate that this is most consistent with a mechanism wherein rate-determining attack of alcohol is facilitated by (DHQD)2AQN acting as a general base. 5-Alkyl 1,3-dioxolanes 52 may also... 

Finally, Scharf and Wolters report a method said to be superior to both the Paal-Knorr synthesis (starting materials more easily accessible) and the Feist-Benary synthesis (freer choice for 3-substituent). Thermal rearrangement-elimination by alkylated dioxolanes at 230 C gives alkyl substituted furans. Yields can be nearly quantitive since the only serious by-products also give the furans under proton-catalyzed thermolysis (Scheme 25).124 Photochemical methods are outlined in Section VII. 

With excess HFA a dioxolaneimine 99a is formed from a typical isonitrile reaction mentioned in previous sections. Acidification yields the unsubstituted five-membered ring 99, which is the parent compound of alkylated dioxolanes 99b-e available from isonitriles (R = Me, Et, t-Bu, c-CgHu) 111, 188). Whether the imine structure 99 or the ketone structure 101 has to be assigned to the hydrolysis product is not known. The Chapman rearrangement has been proved in the following system [Eq. (86)] 190). Treatment of 98 with strong bases like l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) yields a spirocyclic compound 100 with elimination of HCN the structure of 100 has been derived by spectroscopic methods 193). The reaction of 98 with HFA X HjO (91) in sulfuric acid produces a l,3-dioxolan-(4)one 112). 

In the same period, Deng and coworkers also reported that the racemic 5-alkyl l,3-dioxolane-2,4-diones 51 undergo kinetic resolution in the presence of alcohols (ethanol or allyl alcohol) and dimeric cinchona alkaloids such as (DHQD)2AQN (11, 10mol%) [42]. A range of 5-alkyl dioxolanes 51 were highly enantioselectively converted to the (R)-esters (R)-52 (selectivity factors up to 133) (Scheme 11.27). The hydrolysis of the reaction mixture converts the remaining (S)-53 to the (S)-acid (s)-53 that can be easily separated from the (R)-ester 52 by extraction (Scheme 11.27). 

The reaction pattern includes the formation of PO, its consecutive isomerization to propanal, acetone and ally alcohol on acidic sites and combustion [43aj. Propanal and acrolein are also primary products. The formation of lower alkanes, alkenes, acetaldehyde and methanol results from cracking and oxidative C—C bond cleavage of propene and products. Additional side-reactions may occur in the gas phase, including radical-type oxidation of propene to acrolein, hexadiene and other byproducts. Alkyl dioxanes and alkyl dioxolanes may form via dimerization reactions of PO on acidic catalysts. Indeed, major by-products are heavy compounds that... 

Mesityl oxide and hydrogen peroxide react initially to form the cycHc hydroxyalkyl alkyl peroxide, a 1,2-dioxolane. Prolonged equiUbration results in formation of the cycHc di(alkylperoxyalkyl) peroxide, 3,3 -dioxybis(3,5,5-trimethyl-l,2-dioxolane) [4507-98-6] (122,138) ... 

Miscellaneous OC-Substituted Peroxides. 3-Aryl-3-(/ i alkylperoxy)-phthaHdes (12) are prepared from the corresponding 3-chlorophthaHdes and alkyl hydroperoxide (156). 2-Methyl-2-(/ f2 -alkylperoxy)-l,3-benzodioxan-4-ones (13) are obtained from 0-acetylsaHcyloyl chloride and alkyl hydroperoxides (157). Trisubstituted 2-(/ f2 -alkylperoxy)-l,3-dioxolan-4-ones (14) are synthesized from stericaHy favored a-acyloxy acid chlorides and alkyl hydroperoxides (158). 

The kinetics of formation and hydrolysis of /-C H OCl have been investigated (262). The chemistry of alkyl hypochlorites, /-C H OCl in particular, has been extensively explored (247). /-Butyl hypochlorite reacts with a variety of olefins via a photoinduced radical chain process to give good yields of aUyflc chlorides (263). Steroid alcohols can be oxidized and chlorinated with /-C H OCl to give good yields of ketosteroids and chlorosteroids (264) (see Steroids). /-Butyl hypochlorite is a more satisfactory reagent than HOCl for /V-chlorination of amines (265). Sulfides are oxidized in excellent yields to sulfoxides without concomitant formation of sulfones (266). 2-Amino-1, 4-quinones are rapidly chlorinated at room temperature chlorination occurs specifically at the position adjacent to the amino group (267). Anhydropenicillin is converted almost quantitatively to its 6-methoxy derivative by /-C H OCl in methanol (268). Reaction of unsaturated hydroperoxides with /-C H OCl provides monocyclic and bicycHc chloroalkyl 1,2-dioxolanes. 

To synthesize isomeric 3-substituted isoxazoles (301) the reaction of ethylene acetals of )3-ketoaldehydes (300) (readily available from -chlorovinyl ketones (57IZV949)) with hydroxylamine was employed. Owing to the comparative stability of the dioxolane group, this reaction gave exclusively 3-substituted isoxazoles (301) (60ZOB954). The use of noncy-clic, alkyl S-ketoacetals in this reaction resulted in a mixture of 3- and 5-substituted isoxazoles (55AG395). 

Me3SiI, CH2CI2, 25°, 15 min, 85-95% yield.Under these cleavage conditions i,3-dithiolanes, alkyl and trimethylsilyl enol ethers, and enol acetates are stable. 1,3-Dioxolanes give complex mixtures. Alcohols, epoxides, trityl, r-butyl, and benzyl ethers and esters are reactive. Most other ethers and esters, amines, amides, ketones, olefins, acetylenes, and halides are expected to be stable. 

Alkylation of ethyl tnfluoroacetoacetate enolate occurs at the carbon atom provided that the carbonyl function is masked as a dioxolane or an N,N dimeth-ylhydrazone [IIS] (equation 102)... 

The 5-substituted 1,3-dioxolan-4-one 23 is readily deprotonated at the 5 position and can be alkylated with a variety of alkyl halides. The resulting products 24 decompose upon flash vacuum pyrolysis (FVP) at 600°C with loss of acetone... 

The reaction of tertiary alkylthioenyne alcohols (205) with carbon dioxide [70-73 atm, 70-75°C, Cu(I) salts, triethylamine] leads to 4,4-dimethyl-5-(alkyl-thioethenylmethylene)-l,3-dioxolan-2-ones (206) (79KGS1617 79ZOR1319). 

A slightly more complex anti arrhythmic agent is pi rmentol (74). It is synthesized from 4-chloropropiophenone (72) by keto group protection as the dioxolane (with ethylene glycol and acid) followed by sodium iodide-mediated alkylation with cis 2,6-dimethyl pi peri dine to give 7. Deblocking with acid followed by addition of 2-1ithiopyridine completes the synthesis of pi rmentol (74). 

S, 5S, JS)-2-[( 1-Benz yloxyamino)alkyl -4,5-bis[methoxymethyl -2-phenyl-l J-dioxolane ... 

Dioxane reacts with trimethylsilyl iodide 17 to give 96% 1,2-bis-iodoethane, 53% l,2-bis(trimethylsilyloxy)ethane, and 32% HMDSO 7 ]5, 29]. 1,3-Dioxolane 840 furnishes, via 841, iodomethyl-2-iodoethyl ether 842 and HMDSO 7 ]5, 30] (Scheme 6.13). 2-Substituted 1,3-dioxolanes 843 are converted by trimethylsilyl iodide 17, via a series of postulated intermediates, into 1,2-diiodoethane, the ester 844, the alkyl iodide 845, and HMDSO 7 [5] (cf also Chapter 5, Scheme 5.67). 

Accordingly, the cyclopropenylidene anthrones 190/198 were converted by ferric chloride in hydroxylic solvents to the allene ketal 466, whose hydrolysis gives the allenic ketone 46 7288. The dioxolane 468 was obtained from the alkyl-substituted quinocyclopropene 190 in glycol and the ketone 467 in methanol. Apparently FeCl3 served not only as an oxidant, but also as a Lewis acid assisting solvent addition to C1 2 of the triafulvene. 

Chiral glycolates. The chiral dioxolanes 1 and 2 are prepared by reaction of 8-phenylmenthone with a protected derivative, (CH3)3SiOCH2COOSi(CH3)3, of glycolic acid catalyzed by trimethylsilyl triflate. They are obtained in about a 1 1 ratio and are separable by chromatography. Alkylation of the enolates of 1 and 2 proceeds with marked diastereofacial selectivity. After separation of the major... 

The reason that OH does not attack the u-carbon in 63, in contrast to the reaction in Eq. (17), would be due to the stronger electron donation by the /3-carbon in 63, which increases the electron density at the a-carbon atom. Addition of ethylene glycol vinyl ether to the p-toluenesulfonate salt of 64 in CDC13 catalytically yields 2-methyl-1,3-dioxolane (Eq. (18)). The reaction proceeds almost instantaneously, and a 50-fold equivalent of the substrate is completely converted to 2-methyl-1,3-dioxolane, which was confirmed by -NMR. After the reaction, the Pt(III) dimer complex without alkyl ligand is left in the solution, which is still capable of catalysis. The reaction is shown as Eq. (18). 

Furthermore, it has been demonstrated in acetals of phenyl alkyl ketones that the presence of the aromatic moiety at the anomeric carbon induces a further stabilization resulting in very strong anomeric stabilization.29 This phenomenon is reminiscent of the stronger methyl substitution effects discussed above for 1,3-dioxolane and 1,3-dioxane (see also Table 1) than for alkyl ethers and alkanes. 

Co-polymerizations and homo-polymerizations of monomers such as dienes or 4-methylene dioxolan, in which two or more types of ion may propagate simultaneously, are further examples of enieidic polymerizations. These dienes, of course, also provide examples of eniedic radical and anionic polymerizations. Indeed the idea of dieidic polymerization has been suggested by several authors in relation to anionic polymerizations it arose from the aggregation in solution of the lithium alkyls [135], and similar phenomena. 

Dioxanes and dioxolanes, derived from alkyl and aryl aldehydes, react with dichlorocarbene specifically at the C-2 position, with no evidence of reaction at C-4 or C-5 (Scheme 7.2). The yields are variable, but provide a convenient route to dichloromethyl ketones [13, 14], The rate of insertion into the C-H bond correlates with the electronic character of the 2-aryl substituent and is also influenced by... 

A more recent synthesis of 197 [365] is shown in Fig. 9. Enders introduced the stereogenic centre of (S)-lactic acid into the crucial position 10 in 197. The vinylsulfone B, readily available from lactic acid, was transformed into the planar chiral phenylsulfonyl-substituted (q3-allyl)tetracarbonyliron(+l) tetra-fluoroborate C showing (IR,2S,3 )-configuration. Addition of allyltrimethyl silane yielded the vinyl sulfone D which was hydrogenated to E. Alkylation with the dioxolane-derivative of l-bromoheptan-6-one (readily available from 6-bro-mohexanoic acid) afforded F. Finally, reductive removal of the sulfonyl group and deprotection of the carbonyl group furnished 197. A similar approach was used for the synthesis of 198 [366]. 

Treatment of aldehydes or ketones with acceptor-substituted carbene complexes leads to formation of enol ethers [1271-1274], oxiranes [1048], or 1,3-dioxolanes [989,1275] by O-alkylation of the carbonyl compound. Carboxylic acid derivatives... 

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