Chemoselective acetal

The stereoselective reduction of the ketone function of 9 leads to a direct entry to selectively protected aldopentoses ( inversion strategy ) (Borysenko et al. 1989), which greatly expand the potential of this new protocol (Scheme 5). Following Evans protocol the tetramethylammo-nium triacetoxyborohydride-mediated reduction provides the yyn-diol 15 constituting a protected D-ribose (95%, >96% de). The anti-selective reduction to 17 was obtained after silyl protection of the free hydroxyl group of 9 to the OTBS-ether 16 using L-selectride. The aldopentose 18 was then accessible via chemoselective acetal cleavage followed by in situ cyclization (47% over two steps, >96% de). 

Interestingly, Noyori s conditions lead to chemoselective acetalization of the conjugated keto group. ... 

Chemoselective acetalization of an a,(3-unsaturated ketone moiety in the presence of a saturated keto group can also be achieved by using 2,4,6-collidinium / -toluenesulfonate (CPTS) as a catalyst. " ... 

The oxidation of terminal alkenes with an EWG in alcohols or ethylene glycol affords acetals of aldehydes chemoselectively. Acrylonitrile is converted into l,3-dioxolan-2-ylacetonitrile (69) in ethylene glycol and to 3,3-dimetho.xy-propionitrile (70) in methanol[28j. 3,3-Dimethoxypropionitrile (70) is produced commercially in MeOH from acrylonitrile by use of methyl nitrite (71) as a unique leoxidant of Pd(0). Methyl nitrite (71) is regenerated by the oxidation of NO with oxygen in MeOH. Methyl nitrite is a gas, which can be separated easily from water formed in the oxidation[3]. 

With higher alkenes, three kinds of products, namely alkenyl acetates, allylic acetates and dioxygenated products are obtained[142]. The reaction of propylene gives two propenyl acetates (119 and 120) and allyl acetate (121) by the nucleophilic substitution and allylic oxidation. The chemoselective formation of allyl acetate takes place by the gas-phase reaction with the supported Pd(II) and Cu(II) catalyst. Allyl acetate (121) is produced commercially by this method[143]. Methallyl acetate (122) and 2-methylene-1,3-diacetoxypropane (123) are obtained in good yields by the gas-phase oxidation of isobutylene with the supported Pd catalyst[144]. 

The wM-diacetate 363 can be transformed into either enantiomer of the 4-substituted 2-cyclohexen-l-ol 364 via the enzymatic hydrolysis. By changing the relative reactivity of the allylic leaving groups (acetate and the more reactive carbonate), either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. Then the enantioselective synthesis of (7 )- and (S)-5-substituted 1,3-cyclohexadienes 365 and 367 can be achieved. The Pd(II)-cat-alyzed acetoxylactonization of the diene acids affords the lactones 366 and 368 of different stereochemistry[310]. The tropane alkaloid skeletons 370 and 371 have been constructed based on this chemoselective Pd-catalyzed reactions of 6-benzyloxy-l,3-cycloheptadiene (369)[311]. 

Hydroxylysine (328) was synthesized by chemoselective reaction of (Z)-4-acet-oxy-2-butenyl methyl carbonate (325) with two different nucleophiles first with At,(9-Boc-protected hydroxylamine (326) under neutral conditions and then with methyl (diphenylmethyleneamino)acetate (327) in the presence of BSA[202]. The primary allylic amine 331 is prepared by the highly selective monoallylation of 4,4 -dimethoxybenzhydrylamine (329). Deprotection of the allylated secondary amine 330 with 80% formic acid affords the primary ally-lamine 331. The reaction was applied to the total synthesis of gabaculine 332(203]. 

NaSMe, MeOH, 23°, 81-95% yield. This procedure is chemoselective for removal of a thioacetate in the presence of an acetate. 

This chemoselectivity stands in contrast to that of 2,6-disubstituted pyridines. For example, 2,6-dimethylpyridine 35 was reacted with hydrogen peroxide and acetic anhydride to produce the expected acetoxy derivative 36. A second iteration of the previous reaction conditions did not afford an aldehyde, as in the previous example, but 2,6-bis-acetoxy derivative 37. 

Answer There are two acetals here Either could be disconnected first, though not both, since problems of chemoselectivity would arise, Since we have already made piperonal (9) (page T 9) we shall use that as an intermediate. 

Searching for a method of synthesis of enantiopure lamivudine 1, the compound having a monothioacetal stereogenic centre, Rayner et al. investigated a lipase-catalysed hydrolysis of various racemic a-acetoxysulfides 2. They found out that the reaction was both chemoselective (only the acetate group was hydrolysed with no detectable hydrolysis of the other ester moieties) and stereoselective. As a result of the kinetic resolution, enantiomerically enriched unreacted starting compounds were obtained. However, the hydrolysis products 3 were lost due to decomposition." In this way, the product yields could not exceed 50% (Equation 1). The product 2 (R = CH2CH(OEt)2) was finally transformed into lamivudine 1 and its 4-epimer. ... 

Hydroarylation, (addition of H-Ar, Ar = aryl), of alkynes, catalysed by Pd(OOCCH3)2 or Pd(OOCCFj)j in acetic acid, is an atom-economic reaction, giving rise to substituted c/i-stilbenes (Fujiwara reaction). Catalytic conversions and improved chemoselectivity to the mono-coupled product under mild conditions can be achieved by modification of the metal coordination sphere with NHC ligands. Hydroarylation of mesitylene by ethylpropiolate (Scheme 2.19) catalysed by complex 107 (Fig. 2.18) proceeds in good conversions (80-99%, 1 mol%) under mild conditions at room temperature. 

Smaller aldehydes form cyclic acetal-type oligomers readily in aqueous conditions.60 Diols and polyols also form cyclic acetals with various aldehydes readily in water, which has been applied in the extraction of polyhydroxy compounds from dilute aqueous solutions.61 E in water was found to be an efficient catalyst for chemoselective protection of aliphatic and aromatic aldehydes with HSCH2CH2OH to give 1,3-oxathiolane acetals under mild conditions (Eq. 5.7).62... 

Elaboration of triol 88b to bryostatin 7 requires chemoselective hydrolysis of the Cl methyl ester in the presence of the C7 and C20 acetates, macrolide formation, installation of the C13 and C21 methyl enoates, and, finally, global deprotection. The sequencing of these transformations is critical, as attempts to introduce the C21 methyl enoate to form the fully functionalized C-ring pyran in advance of macrolide formation resulted in lactonization onto the C23 hydroxyl. In the event, trimethyltin hydroxide promoted hydrolysis [73] of the Cl carboxylate of triol 88b, and subsequent trie thy lsilylation of the C3 and C26 hydroxyls each occurs in a selective fashion, thus providing the seco-acid 89. Yamaguchi macrolacto-nization [39] proceeds uneventfully to provide the macrolide 67 in 66 % yield (Scheme 5.14). 

The solvent has no influence on the stereoselectivity of bromine addition to alkenes (Rolston and Yates, 1969b), but it could have some effect on the regioselectivity, since this latter depends not only on polar but also on steric effects. Obviously, it modified the chemoselectivity. For example, in acetic acid Rolston and Yates find that 2-butenes give 98% dibromides and 2% solvent-incorporated products whereas, in methanol with 0.2 m NaBr, dibromide is only about 40% and methoxybromide 60%. There are no extensive data, however, on the solvent effects on the regio- and chemoselectivity which would allow reliable predictions. 

Ruasse et al, 1978) is totally regioselective and shows X-dependent chemoselectivity. This is partly in agreement with the kinetic data, which indicate no primary carbocation but rather a competition between the benzylic carbocation and the bromonium ion, depending on X. According to the data of Table 6, bridged intermediates would lead to more dibromide than open ions do. From these results and from those on gem-, cis- or frans-disubstituted alkenes, empirical rules have been inferred for chemoselectivity (i) more solvent-incorporated product is formed from open than from bridged ions (ii) methanol competes with bromide ions more efficiently than acetic acid. 

To summarize, when the kinetic data predict that only bromonium ions or only bromocarbocations are formed, the bromination products are obtained stereospecifically and regiospecifically, respectively, whatever the solvent. Olefin brominations involving open intermediates lead to more solvent-incorporated products in methanol or acetic acid than those involving bridged ions. This chemoselectivity can be interpreted in terms of the hard and soft acid and base theory (Dubois and Chretien, 1978). Methanol assistance to intermediate formation also plays a role in determining product-selectivity (Ruasse et al, 1991). 

In the absence of ZnCl2, the system effects chemoselective reductive cleavage of ally lie acetates.2... 

Allylic alkylation (cf., 12,557). This W(0) complex in combination with 2,2 -bipyridyl (bpy) catalyzes reactions of nucleophiles with allylic acetates or carbonates, but the chemoselectivity is complementary to that of Pd(0), as shown in equation (I). The W(0)-catalyzed reactions are influenced by inductive and steric... 

The nature of the solvent also determines the chemoselective outcome in the reaction products. Products arising from the incorporation of one solvent molecule are formed (besides dibromides) in alcohols, acetic acid and acetonitrile (Id-e), whereas dibromo derivatives are formed exclusively in chlorinated solvents, nitromethane and in ionic liquids. (9) Chemoselectivity depends on the relative nucleophilicity of the solvent and the counterion, although it is affected also by other phenomena (ion pairing, and ion dissociation) in methanol the addition process gives quasi-exclusively bromo-methoxy adducts, whereas in acetic acid dibromides are the main products, formed in addition to smaller amounts of the bromo-acetoxy derivatives. (70)... 

The asymmetric hydroformylation of functionalized aliphatic alkenes is generally more difficult than the hydroformylation of vinyl arenes. The rhodium-catalyzed hydroformylation of vinyl acetate (36) yields 2- and 3-acetoxypropanals, 37 and 38, with high chemoselectivity. Ethyl acetate and acetic acid can also be found as by-products. One of the potential applications of vinyl acetate hydroformylation is the production of enantiopure propane 1,2-diol (Scheme 6). 

While a variety of techniques are available for the monoprotection of symmetrical diols, there are few methods that allow for the chemoselective functionalization of the more hindered hydroxyl in an unsymmetrical 1,3-diol.5 The acid-catalyzed reaction of an unsymmetrically substituted cyclic formal with acetyl chloride described here invariably proceeds via preferential rupture of the less congested C(2)-0 bond to give a product having an acetate at the less congested site... 

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