Intramolecular acetalization

The syntheses of brevicomin (67)[109,110] and frontalin[l 11] have been achieved as an elegant application of the intramolecular acetal formation with the diol 66 in dry DME. Optically active frontalin (68) has been synthesized by this cyclization in triglymejl 12]. 

Intramolecular acetal formation is so favourable that any attempt to make (4) leads at once to frontalin. 

An intramolecular acetal has also been introduced by the treatment of a mixture of a 1-thio-mannoside, having a methoxybenzyl protecting group at C-2 and an alcohol with DDQ [71] (Scheme 4.4c). Activation of the thioglycoside with methyl triflate gave a P-mannoside as the only anomer. This approach was employed for the synthesis of the core pentasaccharide of N-linked glycoproteins. 

Aqueous NaOH (50%, 80 ml) is added to a vigorously stirred solution of the glycoside (5 mmol) and TBA-Br (0.16 g, 0.5 mmol) in CH2Br2 (50 g) at 60-65°C. The reaction is monitored by TLC and, on completion, the organic phase is separated, washed well with H20, dried (MgS04), and evaporated to yield the acetals (replacement of CH2Br2 by CH2Cl2 and reaction temperatures of 25-35°C allows the formation of intermolecular acetals, but not intramolecular acetals). 

As is shown in Scheme 1.2.28, our retrosynthehc analysis led us to the ketodiol 127, providing access to the target pheromone after intramolecular acetalization. It was planned to prepare the dihydroxyketone 127 by diastereoselective ring opening of the epoxide 128 with either enantiomerically pure 3-pentanone SAMP... 

S. J. Angyal and R. J. Beveridge, Intramolecular acetal formation by primary versus secondary hydroxyl groups, Carbohydr. Res., 65 (1978) 229-234. 

Both intramolecular and intermolecular acetalization can occur, although intramolecular acetalization predominates during eady stages of the reaction. Late in the reaction intermolecular acetalization begins to take place when isolated hydroxyl groups from two different polymer chains form acetal linkages. As the level of intermolecular acetalization increases, the resin becomes more difficult to process and gel particles form as cross-linked networks begin to build. 

Vapor phase thermolysis of 2,5-hexadien-l-ols at 260°C affords cyclopropylmethyl ketones . The reaction has been proposed to proceed via homodienyl migration of hydrogen and is stereospecific (equation 118). l-(l-Alkynyl)-2-vinyloxiranes undergo successive Cope rearrangements at 300-350°C to give 2-(l-alkynyl)cyclopropane-carbaldehydes (equation 119) . Acid-catalyzed intramolecular acetalization followed by... 

The cage-like intramolecular acetal structures of 77 and 78 attracted my attention, and we synthesized both ( )-77 and ( )-78, the former of which showed the spectral data identical to those of the natural lineatin.33,34 Photocycloaddition of vinyl acetate to 3-methyl-2-cyclopentenone (A) gave B, from which were prepared two isomeric ketones C and D. These were separable by chromatography, and their structures could be determined by -NMR analysis. The ketone ( )-C was further converted to ( )-77, while ( )-D... 

From the above discussion, it is obvious that the conformer 48a will predominate and the conformer 48c will contribute insignificantly to the equilibrium mixture. In other words, l,9-dihydroxy-5-nonanone 47 will generate, on being subjected to intramolecular acetal formation reaction under acidic condition, an equilibrium mixture of the three spiroacetals wherein the conformer 48a must predominate. 

The synthesis starts from the natural raw material manool, which is obtained by extraction from a tree growing in New Zealand, the so-called pink pine, Halocarpus biformis (Hooker) C.J. Quinn. Epoxidation of manool, subsequent oxidative degradation of the allylalcohol side chain to yield a ketone, and intramolecular acetalization afford the ketal [193d],... 

Fig. 21. Intramolecular side reactions during hydrolysis of 2-O-hydroxalkyl and 2-O-allyl ethers of glucans. Intramolecular acetal or addition product formation., favored isomer and conformation according to Lee and PerUn. l,2-0-[l,2-methyl-(5,i )-l,2-ethanediyl]-a-D-glucofuranoses and l,2-0-[l,2-methyl- 5)-l,2-ethanediyl]-a-D-glucopyranose are also formed in equilibria.

This simple reactivity can be developed in many more elaborate ways you can read about elsewhere, but simple examples include hydration of an enyne to form a conjugated ketone and the capture of the ketone by intramolecular acetal formation. The details give you an idea of reagents, solvents, and yields. 

Leighton constructed the complex molecule of the CP-263,114 core ring system 641 by elegant application of Pd-catalyzed carbonylation of the 1,3-butadienyl 2-triflate moiety in 637 via the methylene-7r-allylpalladium 638 to afford the unsaturated lactone 640. The lactone was subjected to Cope rearrangement to produce 641 as shown by 640 in 56 % overall yield. Formation of the unsaturated lactone 640 by intramolecular acetalization involving the alcohol, ketone, and acylpalla-dium as shown by 639, is a key reaction [228]. 

Figure 29. Hydroformylation-intramolecular acetalization of allylic alcohols...

Figure 30. Different allylic alcohols studied in hydroformylation-intramolecular acetalization...

Two minor products formed during the oxidation of colupolone (193) with molecular oxygen have been shown to have structures (195) and (196). The main product of oxidation is cohulopone (194), and (195) and (196) are considered to be derived from (194) by epoxidation and subsequent opening of the oxiran ring and intramolecular acetalization. ... 

The (2 )-methoxymethylidene-l,6-dioxaspiro[4,5]-decane skeleton (36) was constructed in a highly stereoselective manner by a palladium(II)-catalyzed cycliza-tion-alkoxycarbonylation sequence starting from the 3,4-dioxygenated-9-hydroxy-l-nonyn-5-one (35). The use of a catalytic amount of Pd(0) and a high excess of p-benzoquinone was essential to minimize the amount of the active palladium(II) catalyst in the reaction mixture and to prevent intramolecular acetal formation, leading to 37 as a side reaction [49]. 

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