Thermal epimerization of inositol 1,3-benzylidene acetals in the molten state

1,3-O-Benzylidene-2,4,5,6-tetra-O-substituted-myo-inositol derivatives obtained by the DIBAL-H reduction of the corresponding myo-inositol 1,3,5-orthobenzoate derivatives undergo epimerization at the acetal carbon on heating, in the molten state, just above their melting point. The same epimerization reaction does not proceed either in the crystalline state or in solution. DFT calculations suggest that the epimeric acetal obtained by this thermal process is relatively more stable than the starting acetal. Either of these acetals could not be obtained by the reaction of the corresponding inositol derived diol with benzaldehyde. These observations constitute a novel reaction solely in the molten state, which are rarely encountered in the literature. X-ray crystal structures of the epimeric acetals as well as their radical deoxygenation reaction are also reported.     

13C NMR study of the structures of some acyclic and cyclic ketene acetals

A ¹³C NMR study of the spatial structures of some acyclic and cyclic ketene acetals (for example, ketene dimethyl acetal and 2-methylene-1,3-dioxolane) has been carried out. The conclusions obtained are based on observation of the effect of structural changes on the ¹³C NMR chemical shift of the β carbon on the ketene moity. Since the extent of p-π conjugation and hence the ¹³C chemical shift of this carbon depend on the spatial orientation of the alkoxy groups about the O-C(sp²) bonds, the shift concerned may be used as a measure of the planarity of the system. The most stable retamers of ketene dimethyl acetal are s-cis,s-cis (planar) and s-cis,gauche (slightly nonplanar), in the order of decreasing stability. For ketene dialkyl acetals, the relative stability of the planar s-cis,s-cis form decreases with increasing bulkiness of the alkyl groups, but at least for primary and secondary alkyl groups, the s-cis,s-cis rotamer appears to be the most favored species. The conformations of 5- to 8-membered cyclic ketene acetals are discussed and compared with those of the corresponding cyclic vinyl ethers and hydrocarbons.     

Inter- and intramolecular differentiation of enantiotopic dioxane acetals through oxazaborolidinone-mediated enantioselective ring-cleavage reaction: kinetic resolution of racemic 1,3-alkanediols and asymmetric desymmetrization of meso-1,3-polyols

Acetals derived from racemic 1,3-alkanediols undergo kinetic resolution in chiral oxazaborolidinone-mediated ring-cleavage reaction with nucleophiles such as enol silanes and allylic silanes. Enantioselectivity of the reaction is affected by nucleophiles, the N-sulfonyl groups of oxazaborolidinones, and the substituents attached to the acetal carbon. For disubstituted acetals rac-1 and for trisubstituted acetal rac-2, derived from syn-2,4-dimethyl-1,3-pentanediol, satisfactory enantioselectivity is obtained by using methallylsilane 7b,c as a nucleophile in combination with N-mesyloxazaborolidinone 4a. On the other hand, enantioselective reaction of trisubstituted acetal rac-3b, derived from anti-2,4-dimethyl-1,3-pentanediol, is realized by using silyl ketene acetal 5e in combination with N-tosyloxazaborolidinone 4b. The reaction conditions optimized for the kinetic resolution, or enantiomer differentiating reaction, of the racemic acetals are successfully applied to asymmetric desymmetrization of meso-1,3-polyols through intramolecular differentiation of the enantiotopic acetal moieties of the bis-acetal derivatives. The utility of the ring-cleavage reaction as a method for enantioselective terminal differentiation of prochiral polyols is demonstrated in convergent asymmetric synthesis of pentol derivative 35 corresponding to the C(19)[bond]C(27) ansa-chain of rifamycin S.     

Efficient one-step aldol-type reaction of ketones with acetals and ketals mediated by dibutylboron triflate/diisopropylethyl amine

one-step Mukaiyama aldol type reaction [reaction: see text] A highly efficient one-step Mukaiyama aldol-type reaction has been developed for the synthesis of beta-alkoxy carbonyl compounds starting from ketones and acetals/ketals. The reaction is mediated by a combination of Bu(2)BOTf and i-Pr(2)NEt affording the products in high yields. Formation of the two possible diastereoisomers of the beta-alkoxy ketones from the chiral acetals shows that the condensation takes place by an S(N)1 mechanism, involving prior opening of the acetal to an oxonium ion.     

Catalytic enantioselective synthesis of quaternary stereocenters via intermolecular C-acylation of silyl ketene acetals: dual activation of the electrophile and the nucleophile

A nucleophile-catalyzed asymmetric intermolecular C-acylation of silyl ketene acetals by anhydrides has been developed, furnishing quaternary stereocenters with high enantioselectivity. Mechanistic studies support the hypothesis that the reaction involves activation both of the silyl ketene acetal (generation of an enolate) and of the anhydride (formation of an acylpyridinium ion).     

Unzipping and scrambling reaction-induced sequence control of copolymer chains via temperature changes during cationic ring-opening copolymerization of cyclic acetals and cyclic esters

A temperature change-dependent sequence transformation of copolymer chains was demonstrated by a method based on tandem depolymerization and transacetalization reactions during the cationic ring-opening copolymerization of cyclic acetals and cyclic esters. In this study, the position of polymerization-depolymerization equilibrium was controlled by the reaction temperature rather than by the decrease in monomer concentration under vacuum conditions, as in our previous study. First, the conditions for efficient copolymerization were optimized, with a particular focus on the structures of cyclic acetals and cyclic esters. Subsequently, sequence transformation induced by temperature change was examined during the copolymerization of 2-methyl-1,3-dioxepane (generated in situ from 4-hydroxybutyl vinyl ether) and δ-valerolactone using EtSO₃H. The homosequence length of cyclic acetals decreased during depolymerization (unzipping) at the oxonium chain ends upon increasing the temperature from 30 to 90 °C, while transacetalization (scrambling) of the main chain transferred midchain cyclic acetal homosequences to the oxonium chain ends. As a result of the cycle of unzipping and scrambling reactions, an alternating-like copolymer was obtained. Interestingly, the possibility of reversible sequence transformation upon heating and cooling was also demonstrated.     

Comparison between electron transfer and nucleophilic reactivities of ketene silyl acetals with cationic electrophiles

The products and kinetics for the reactions of ketone silyl acetals with a series of p-methoxy-substituted trityl cations have been examined, and they are compared with those of outer-sphere electron transfer reactions from 10,10'-dimethyl-9,9', 10, 10'- tetrahydro-9,9'-biacridine [(AcrH)2] to the same series of trityl cations as well as other electron acceptors. The C-C bond formation in the reaction of beta,beta-dimethyl-substituted ketene silyl acetal (1: (Me2C=C(OMe)OSiMe3) with trityl cation salt (Ph3C+ClO4-) takes place between 1 and the carbon of para-positon of phenyl group of Ph3C+, whereas a much less sterically hindered ketene silyl acetal (3: H2C=C(OEt)OSiEt3) reacts with Ph3C+ at the central carbon of Ph3C+. The kinetic comparison indicates that the nucleophilic reactivities of ketene silyl acetals are well correlated with the electron transfer reactivities provided that the steric demand at the reaction center for the C-C bond formation remains constant.     

Diastereoselection in 1,3-O- to -C-alkyl migration reaction of 1-alkenyl alkyl acetals catalyzed by boron trifluoride etherate

Remarkable diastereoselection, with (E)-alkenyl alkyl acetal giving selectively the erythro α-alkyl-β-alkoxyaldehyde, and (Z)-acetal leading preferentially to the threo isomer, is observed in the 1,3-O- to - C-alkyl migration reaction of 1-alkenyl alkyl acetals catalyzed by boron trifluoride etherate.     

Catalytic enantioselective construction of all-carbon quaternary stereocenters: synthetic and mechanistic studies of the C-acylation of silyl ketene acetals

With the aid of an appropriate chiral catalyst, acyclic silyl ketene acetals react with anhydrides to furnish 1,3-dicarbonyl compounds that bear all-carbon quaternary stereocenters in good ee and yield. Mechanistic studies provide strong support for a catalytic cycle that involves activation of both the electrophile (anhydride --> acylpyridinium) and the nucleophile (silyl ketene acetal --> enolate).     

Mukaiyama addition of (trimethylsilyl)acetonitrile to dimethyl acetals mediated by trimethylsilyl trifluoromethanesulfonate

(Trimethylsilyl)acetonitrile reacts smoothly with dimethyl acetals in the presence of stoichiometric trimethylsilyl trifluoromethanesulfonate (TMSOTf) to yield β-methoxynitriles. The ideal substrates for this reaction are acetals derived from aromatic aldehydes. Elimination to the corresponding α,β-unsaturated nitriles is observed as the major product in the case of electron-rich acetals. A mechanistic hypothesis that includes isomerization of the silylnitrile to a nucleophilic N-silyl ketene imine is presented.     

Reactions of cyclopropanone acetals with alkyl azides: carbonyl addition versus ring-opening pathways

The Lewis acid-mediated reactions of substituted cyclopropanone acetals with alkyl azides were found to strongly depend on the structure of the ketone component. When cyclopropanone acetal was treated with alkyl azides, N-substituted 2-azetidinones and ethyl carbamate products were obtained, arising from azide addition to the carbonyl, followed by ring expansion or rearrangement, respectively. When 2,2-dimethylcyclopropanone acetals were reacted with azides in the presence of BF3.OEt2, the products obtained were alpha-amino-alpha'-diazomethyl ketones, which arose from C2-C3 bond cleavage of the corresponding cyclopropanone, giving oxyallyl cations that were captured by azides. Aryl-substituted cyclopropanone acetals, when subjected to these conditions, afforded [1,2,3]oxaborazoles exclusively, which were also the result of C2-C3 bond rupture, azide capture, and then loss of nitrogen. In the reactions of n-hexyl-substituted cyclopropanone acetals with alkyl azides, a mixture of 2-azetidinones and regioisomeric [1,2,3]oxaborazoles was obtained. The reasons for the different behavior of the various systems are discussed.     

Rhenium-catalyzed reaction of carbonyl compounds with ketene silyl acetals

It was found that rhenium complex is an effective catalyst for the reaction of carbonyl compounds with ketene silyl acetals. A wide range of β-silyloxy esters is obtained by the treatment of carbonyl compounds with ketene silyl acetals in the presence of a catalytic amount of ReBr(CO)₅ in moderate to good yields.     

Theoretical studies of five-membered ring ketene acetals

Cyclic ketene acetals are a class of organic molecules characterized by a nucleophilic exo-methylene carbon attached to a carbon with two adjacent O, N, or S atoms. We have carried out a systematic computational study of a series of five-membered cyclic acetals like 2-methylene-1,3-dioxolane and its OS, SS, NO, NS, and NN analogs as well as all the protonated species. The calculations were performed at the MP2 level using a triple zeta plus polarization basis set. The nucleophilicity was discussed in terms of geometrical factors, calculated atomic charges, calculated chemical shifts, and proton affinities. All the six neutral species were strong nucleophiles. The NN analog was predicted to be the strongest and the SS analog the weakest nucleophile.     

Co2(CO)8-catalyzed carbonylation of acetals using N-silylamines

Formaldehyde dialkyl acetals and cyclic acetal, 1,3-dioxolane, are smoothly carbonylated using N-silylamines at 140–160 °C under 70–88 kg cm⁻² CO pressure in the presence of a catalytic amount of Co₂(CO)₈ to give the corresponding 2-alkoxyamides in moderate to good yields. In the carbonylation of formaldehyde dialkyl acetals using N-silylamines, addition of pyridine drastically enhances the catalytic activity.     

Protected ester,nitrile, carbinol and carbinyl amine cyclopropanone hydrates

Methyl diazoacetate reacted with the ketene acetal I in the presence of dirhodium tetraacetate yielding the metastable cyclopropanone ketal ester II, which was converted to the primary and tertiary cyclopropyl carbinols III and IV by treatment with lithium aluminum hydride and methyl lithium, respectively. Diazoacetonitrile yielded a stable crystalline cyclopropanone ketal nitrile X following reaction with the ketene acetal I.     

A dipole moment study of the structures of some ketene acetals

The dipole moments of several acyclic and cyclic ketene acetals have been determined in benzene solution at 293 K using the Halverstadt-Kumler method. For ketene dialkyl acetals (alkyl = Me, Et) the results point to a predominance of the s-cis,s-trans retamer, which disagrees with the conclusions drawn previously from ¹³C NMR chemical shift data, i.e. the s-cis,s-cis form is the more stable species. In the case of 2-methoxyfuran, the dipole moment measurements confirm the previous findings based on the ¹³C NMR spectra, viz the s-cis form is the predominating rotamer. The dipole moments and structures of some other ketene acetals are also discussed.     

The use of carbon black-supported sulfuric acid to initiate the cationic polymerization of cyclic ketene acetals

Stable polymers were made by the cationically initiated 1,2-polymerization of cyclic ketene acetals employing heterogeneous, activated carbon-supported sulfuric acid catalysts. A methodology has been established for the preparation of the carbon black of different acidic strengths. By adjusting either the acid strength or the amount of carbon black used, cyclic ketene acetals with different activities can be polymerized efficiently to form stable high molecular weight polymers. This methodology will be a useful tool for polymerization, copolymerization, and studies of the relative reactivities of the cyclic ketene acetals. The polymer structures were determined by FTIR, ¹³C-NMR, and ¹H-NMR studies. © 1996 John Wiley & Sons, Inc.     

Lewis base activation of lewis acids. Addition of silyl ketene acetals to aldehydes

The weak Lewis acid silicon tetrachloride can be activated by catalytic amounts of the chiral bisphosphoramide (R,R)-3 to form a highly reactive, chiral trichlorosilyl cation which is an extremely effective promoter of aldol addition reactions between aldehydes and silyl ketene acetals. The tert-butyldimethylsilyl ketene acetal of methyl acetate adds nearly instantaneously to aromatic and olefinic aldehydes as well as aliphatic aldehydes (albeit more slowly) with excellent enantioselectivity. The homologous tert-butyldimethylsilyl ketene acetal of tert-butyl propanoate adds with nearly exclusive anti diastereoselectivity to a similar range of aldehydes also with excellent enantioselectivity. The origin of the slower reaction rate with aliphatic aldehydes is revealed to be the formation of chlorosilyl ether adducts.     

9-Anthraldehyde acetals as protecting groups

Anthraldehyde acetals can be introduced regioselectively to carbohydrates in high yields. Advantages over conventional acetal protecting groups are increased crystallinity and strong absorbance and fluorescence which facilitate purification and reaction monitoring. The anthraldehyde acetals can be deprotected selectively in the presence of benzylidene acetals and can be cleaved regioselectively to yield 6-O-(9-anthracenyl)methyl ethers.     

Utilization of 1-oxa-2,2-(dimesityl)silacyclopentane acetals in the stereoselective synthesis of polyols

We have developed a route for the stereoselective synthesis of 1-oxa-2,2-(dimesityl)silacyclopentane acetals, intermediates in the synthesis of highly functionalized 1,3-diols. This route involves a diastereoselective conjugate addition reaction of a hydrosilyl anion, a subsequent diastereoselective enolate alkylation, and a fluoride-catalyzed intramolecular hydrosilylation reaction to afford the oxasilacyclopentane acetal. A highly selective nucleophilic substitution reaction, followed by oxidation of the C-Si bond, leads to the desired polyol.