4,6-Alkylidene acetal

Its trapping with various electrophiles provides chiral products, such as 137-139. The deprotection of 139 furnishes the -alkynylaldehyde 140 in 88% ee. The exo-alkylidene acetal 141 is converted similarly to the zinc reagent 142, which can be allylated with an excellent diastereoselectivity (d.r. = 96 4) leading to the ketal 143 (Scheme 44) " . 

In order to decide stereochemical problems, alkylidene acetals of carbohydrates should be studied, the structure of these compounds being dependent on the stereochemistry of the parent monosaccharide molecule. Since the structure of the alkylidene acetal can sometimes be elucidated from the mass spectrum, the latter also provides evidence regarding the stereochemistry of the carbohydrate molecule started with. 

Unsaturated benzylidene and alkylidene acetals, under methoxycarbonylation conditions, give tetrahydro-2//-pyran-2-acetates in low to good yield. Moderate stereoselectivity is observed in the cyclization and the ra-2,6-disubstituted isomer is predominant in the reaction mixture. The preferred 2,6-cis relationship can be ascribed to the 2,6-diequatorial orientation of the substituents on the tetrahydro-2//-pyran ring83. 

Some other alkyliden acetals with atypical properties have been used as protecting groups in carbohydrate chemistry. Thus, phenylsulfonylethylidene (PSE) acetals can be s)mthesized from glycosides under basic conditions. These derivatives are suitable for the protection of... 

Emil Fischer first described the condensation of D-fructose with acetone in 1895, and most of the early work on cyclic acetals of ketoses was performed with D-fructose. In 1934, Reichstein and Griissner published their classic synthesis of L-ascorbic acid (vitamin C), in which L-sorbose was converted into 2,3 4,6-di-0-isopropylidene-a-L-sorbofuranose or other di-alkylidene acetals. The emphasis of research activity then shifted to L-sorbose, and to the elucidation of an optimal procedure for preparing such diacetals. At about the same time, Levene and Tipson used isopropylidene acetals as derivatives for the purification of L-cri/thro-pentulose (as the di-isopropylidene acetal) and D-thrco-pentulose (as the monoisopropyli-dene acetal). Soon thereafter, Reichstein and coworkers used diisopropylidene acetals of D- and L-psicose, and D-tagatose, to purify the respective sugars. 

At mutarotational equilibrium in water, D-fructose (51) exists preponderantly as the j8-D-pyranose anomer in the 1C(d) conformation. A 1,2-alkylidene acetal (52) is formed in the same way as for L-sorbose, but this monoacetal has cts-disposed hydroxyl groups at C-4 and C-5 that react readily, forming a l,2 4,5-di-0-alkylidene-)8-D-fructopyranose (53). No evidence is available to indicate that the 1,2-alkylidene acetal might rearrange to a 1,3-alkylidene acetal, and it is to be expected that the activation energy for this isomerization would exceed that for formation of an acetal at 0-4 and 0-5. 

On treatment with a non-enolizable aldehyde and sodium hydride, rruns-related a-hydroxyepoxides were converted to acetals. The reaction is thought to proceed by way of a hemiacetal salt, as illustrated in Scheme 2. L-Galactono-1,4-lactone, a by-product of the sugar industry, furnished a diastereomeric mixture of 5,6-alkylidene acetals 18 in >60% yield on microwave irradiation in the presence of long-chain aldehydes and montmorillonite KSF as catalyst, and 4,6-O-alkylidene derivatives 19 of D-glucose have been prepared by use of long-chain aldehydes and catalytic pyridinium />-toluenesulfonate in benzene under azeotropic removal of water. Compounds 18 and 19 were of interest in liquid crystal studies. 

The alkylidene dimethone (dimedone) (I) upon boiling with glacial acetic acid, acetic anhydride, hydrochloric acid and other reagents frequently loses water and passes into a substituted octahydroxanthene or the anhydride (II), which often serves as another derivative. The derivatives (I) are soluble in dilute alkali and the resulting solutions give colourations with ferric chloride solution on the other hand, the anhydrides (II) are insoluble in dilute alkali and hence can easily be distinguished from the alkylidene dimedones (I). 

Alkoxythiazoles are prepared by heterocyclization (274, 462). The Williamson method using catalytic amounts of KI and cupric oxide is also possible (278. 288, 306). 5-Acetoxy-4-alkenylthiazoles are obtained by treatment of 242 with acetyl chloride and triethylamine or with acetic anhydride and pyridine (450). Similarly, the reaction of diphenylketene with 242 affords 5-acyloxy-4-alkenylthiazoles (243) (Scheme 120) (450). The readiness of these o-acetylations suggests that 4-alkylidene thiazoline-5-one might be in equilibrium with 4-alkenyl-5-hydroxythiazoles (450). 

Conjugate dcLiicii of nkro ilkdnes to illyl Baylis-Hillman acetates in the pesence of NaOH (0.6 N in THF ves 2-alkylidene-4-nitro ketones with high sieteoselecdvity these are convened via the Nef teacdon into the conesponding 1,4-diketones fEq. 4.1... 

With the exocyclic alkylidene at C-13 properly in place, the elaboration of the l,5-diyn-3-ene moiety can now be addressed. Cleavage of both acetate and trimethylsilyl functions in 86 with basic methanol, followed by triethylsilylation of the newly formed tertiary hydroxyl group, efficiently affords alkyne 25 (86 % overall yield). This substance was regarded as a viable candidate for a Pd-catalyzed coupling reaction.12 Indeed, treatment of 25 with (Z)-chloroenyne 26 in the presence of a catalytic amount of Pd(PPh3)4 and Cu1 results in the formation of enediyne 24 in 91 % yield. 

Wang et al. reported that FeCls- and FeBrs-promoted cyclization/halogenation of alkynyl diethyl acetals formed ( )-2-(l-halobenzylidene or alkylidene)-substi-tuted five-membered carbo- and heterocycles. It was found that the 1 1 molar ratio... 

Finally, Larock and coworkers [34] recently reported on an efficient synthesis of 9-alkylidene- and 9-benzylidene-9H-fluorenes 6/1-47, again using 6/1-42 and 6/1-43 as substrates. The best results were obtained with sodium acetate and Bu4NC1, which allowed 6/1-47 to be obtained in 62 % yield. A proposed mechanism is given in Scheme 6/1.9, suggesting a migration of palladium from a vinylic to an arylic position [35]. 

Conjugate addition of nitroalkanes to ailyl Baylis-Hillman acetates in the presence of NaOH (0.6 N) in THF gives 2-alkylidene-4-nitro ketones with high stereoselectivity these are converted via the Nef reaction into the corresponding 1,4-diketones (Eq. 4.119).164... 

The ruthenium carbene catalysts 1 developed by Grubbs are distinguished by an exceptional tolerance towards polar functional groups [3]. Although generalizations are difficult and further experimental data are necessary in order to obtain a fully comprehensive picture, some trends may be deduced from the literature reports. Thus, many examples indicate that ethers, silyl ethers, acetals, esters, amides, carbamates, sulfonamides, silanes and various heterocyclic entities do not disturb. Moreover, ketones and even aldehyde functions are compatible, in contrast to reactions catalyzed by the molybdenum alkylidene complex 24 which is known to react with these groups under certain conditions [26]. Even unprotected alcohols and free carboxylic acids seem to be tolerated by 1. It should also be emphasized that the sensitivity of 1 toward the substitution pattern of alkenes outlined above usually leaves pre-existing di-, tri- and tetrasubstituted double bonds in the substrates unaffected. A nice example that illustrates many of these features is the clean dimerization of FK-506 45 to compound 46 reported by Schreiber et al. (Scheme 12) [27]. 

The utilization of copper complexes (47) based on bisisoxazolines allows various silyl enol ethers to be added to aldehydes and ketones which possess an adjacent heteroatom e.g. pyruvate esters. An example is shown is Scheme 43[126]. C2-Symmetric Cu(II) complexes have also been used as chiral Lewis acids for the catalysis of enantioselective Michael additions of silylketene acetals to alkylidene malonates[127]. 

Ring opening reaction of alkylidenecyclopropanone acetals readily proceeds in the presence of Lewis or Bransted acids to produce l-alkylidene-2-oxyallyl cation, which is provided for the reaction with nucleophiles such as chloride, alcohols, siloxyalkenes, and furans. The reaction of this cation with the carbon nucleophiles gives products of [4 + 3] and [3 + 2] cycloaddition as well as those of nucleophilic addition. The modes of addition reactions are controlled by the oxy group of the cation and by the reaction conditions including solvent. 

Alkylidene cyclohexenes were synthesized stereoselectively from bis-allyl silylketene acetals derived from cyclohexenones93. As shown in equation 66, Ireland Claisen rearrangement of ester 133 gave only E-diene 136. Reaction of 133 with potassium... 

The C=C bond in a 5-(alkylidene)oxazoline 644 is activated for electrophilic reactions similar to that in analogous vinyl acetates. Rohm Haas researchers exploited this property to prepare chloromethyl ketone fungicides 646 (Scheme 8.203). The overall process constitutes an indirect chlorination of a-amido ketones since the 5-(vinylidene)oxazolines were prepared from a-amido ketones. 

Other electron-withdrawing groups are compatible with diazo transfer and cyclization, Both the / -keto sulfone 9 and the /J-keto phosphonate 11 have been cyclized using rhodium acetate catalysis4 8,49. The cyclized keto phosphonate 12 can be further reacted49 with formaldehyde to yield the a-alkylidene cyclopentanone 13. 

Matsuda independently developed an alternative procedure for the cyclization/silylformylation of enynes that did not require the use of phosphite ligand, and which was effective with low catalyst loading. As an example, reaction of a benzene solution of acetal 65 (0.1 M) and dimethylphenylsilane catalyzed by Rh(acac)(GO)2 (0.005 mol%) under GO (20 bar) at 90 °G for 14 h formed silylated alkylidene carboxaldehyde 66 in 89% yield (Equation (44)). 

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