Lewis acids reaction with cyclic acetals

In cationic polymerizations, electron-deficient initiators (mostly Bronsted or Lewis acids) react with electron-rich monomers. The active chain end (ACE) bears a positive charge with the active sites being either carbenium or 0x0-nium ions. Molecular weights are often limited by the inherent sensitivity to impurities, chain transfer, and rearrangement reactions. Suitable monomers for cationic polymerizations are vinyl monomers with electron-donating moieties or cyclic structures containing heteroatoms, while the latter case is termed cationic ROP. Eligible monomers include cyclic ethers, acetals, and amines as well as lactones and lactams (Scheme 3). 

The scope of this reaction is similar to that of 10-21. Though anhydrides are somewhat less reactive than acyl halides, they are often used to prepare carboxylic esters. Acids, Lewis acids, and bases are often used as catalysts—most often, pyridine. Catalysis by pyridine is of the nucleophilic type (see 10-9). 4-(A,A-Dimethylamino)pyridine is a better catalyst than pyridine and can be used in cases where pyridine fails. " Nonbasic catalysts are cobalt(II) chloride " and TaCls—Si02. " Formic anhydride is not a stable compound but esters of formic acid can be prepared by treating alcohols " or phenols " with acetic-formic anhydride. Cyclic anhydrides give monoesterified dicarboxylic acids, for example,... 

Acetal handle 78 synthesized from Merrifield resin and 4-hydroxy-benzaldehyde was applied to the solid-phase synthesis of carbohydrates and 1-oxacephams (Scheme 41) [90]. For the latter, a 1,3-diol was initially anchored to the support to form a cyclic acetal. A ring opening reaction with DIBAL generated a resin-bound alcohol which was converted to the corresponding triflate for A-alkylation with 4-vinyl-oxyazetidin-2-one. A Lewis acid catalyzed ring closure released 1-oxa-cephams from the support. 

Cyclization of mixed acetals (13,300).4 This reaction is a particularly useful route to eight-membered cyclic ethers (oxocanes) and provides the first practical route to a natural oxocene, (- )-laurenyne (3), from an optically active mixed acetal 1. Thus cyclization of 1 followed by O-desilylation affords 2 as the only cyclic product. Remaining steps to 3 involved C-desilylation, for which only HF/pyridine is useful, introduction of unsaturation into the C2-side chain, and extension of the C8-side chain. Exploratory studies showed that unsaturation at the p- or y-positions to the cite of cyclization of 1 prevent or retard cyclization with a wide variety of Lewis acids. The cyclization is apparently more tolerant of substitution in the terminator position, C3-Q, of the oxocene. 

Acetalation. As polyhydroxy compounds, carbohydrates react with aldehydes and ketones to form cyclic acetals (1,13). Examples are the reaction of D-glucose with acetone and a protic or Lewis acid catalyst to form l,2 5,6-di-0-isopropylidene-a-D-glucofuranose [582-52-5] and its reaction with benzaldehyde to form 4,6-O-benzylidene-D-glucopyranose [25152-90-3]. The 4,6-0-(l-carboxyethylidine) group (related to pyruvic acid) occurs naturally in some polysaccharides. 

Because of the special structural requirements of the resin-bound substrate, this type of cleavage reaction lacks general applicability. Some of the few examples that have been reported are listed in Table 3.19. Lactones have also been obtained by acid-catalyzed lactonization of resin-bound 4-hydroxy or 3-oxiranyl carboxylic acids [399]. Treatment of polystyrene-bound cyclic acetals with Jones reagent also leads to the release of lactones into solution (Entry 5, Table 3.19). Resin-bound benzylic aryl or alkyl carbonates have been converted into esters by treatment with acyl halides and Lewis acids (Entry 6, Table 3.19). Similarly, alcohols bound to insoluble supports as benzyl ethers can be cleaved from the support and simultaneously converted into esters by treatment with acyl halides [400]. Esters have also been prepared by treatment of carboxylic acids with an excess of polystyrene-bound triazenes here, diazo-nium salts are released into solution, which serve to O-alkylate the acid (Entry 7, Table 3.19). This strategy can also be used to prepare sulfonates [401]. 

Cyclization to a morpholinolactone (59) occurs in the hydrolysis reaction of the di-A-hydroxylethylated compound (60). Compound (59) is rapidly hydrolysed by water to (61) but in file presence of equimolar amounts of amines (RNH2) or ammo acid derivatives (62) forms.56 A novel reaction of cyclic 2-diazo-l,3-dicarbonyl compounds (63) with lactones (64) affords the products (65) in the presence of rhodium acetate, Rh2(OAc)4.57 Lewis acid-promoted intramolecular additions of allylsilanes to lilac tones gave substituted cyclopentanes.58 A proposed transition state guided efforts to improve the stereoselectivity of the reaction. The reaction of a series of /1-lactone derivatives, such as (66)-(68), has been studied and they have been ling cleaved the reaction outcome is both Lewis acid and structure dependent.59... 

The best solvent, temperature, and Lewis acid conditions for the Sn reactions of CRS)-l-(2-mtrobenzenesulfonyl)- and (7 5 )-l-(4-nitrobenzenesulfonyl)-3-methoxy-l,2,3,5-tetrahydro-4,l-benzoxazepines with silylated 5-fluorouracil and uracil129 proved to be SnCL at 50 °C in MeCN. The more nucleophilic silylated uracil reacts faster at its N(3) atom giving mainly the cyclic 0,N-acetal (by C-OMe cleavage). The silylated 5-fluorouracil, on the other hand, reacts at its less sterically hindered N(l) atom and gives mainly an acyclic product (by ring C-0 cleavage). Calculations at the HF/6-31G level of theory support the experimental observations. 

Two examples using azo compounds in allylic amination reactions will be presented in the following. Leblanc et al. have used the more reactive trichloro derivative 82 of DEAD, 81, and found that the ene reaction proceeds at various temperatures and without any Lewis acid catalyst present, for both cyclic and acyclic alkenes to give allyl amines in good yields. The reaction of the alkene 85 with 82 gave the allylic aminated compound 86 in 85 % yield (trans. cis = 85 15) (Eq. (21)) [53f. The allyl amine 87 was formed in good yield after treatment with a suspension of zinc powder in acetic acid solution. 

Lactols and their acetals can be transformed easily into their 2-arylsulfonyl derivatives 337 by reaction with a sulfinic acid under Lewis acid activation. The corresponding organolithiums are prepared by deprotonation with n-BuLi or LDA and, after reaction with electrophiles, a /(-elimination of sulfinic acid afforded a cyclic a-substituted enol ether514,547,548. 2-Lithio-2-(arylsulfonyl)tetrahydropyrans equilibrated to give mainly the anomer with the lithium atom at the equatorial position549. 

During a synthesis of the Chlorothricolide, Roush and Sciotti encountered unexpected problems with the hydrolysis of the dimethyl acetal 54.1 [Scheme 2.54].112 Use of some of the standard hydrolysis conditions (oxalic acid, PPTS, PTSA, HO Ac, or trifluoroacetic acid — all in acetone) resulted in recovery of 54.1 or decomposition. Success was achieved by exploiting the mild Lewis acidic properties of the lithium cation under conditions first reported by Lipshutz and Harvey.113 Thus treatment of the dimethyl acetal 54,1 with lithium tetrafluoroborate in acetonitrile containing 2% water returned the desired aldehyde 54J in 97% yield after 2 h at room temperature. The reaction was also applied to the deprotection of a cyclic ketal in a synthesis of Pumi-liotoxin.114 115... 

Alkenylsilanes and -stannanes, and arylsilanes and -stannanes are useful reagents for transfer of an sp -carbon unit to electrophiles under titanium catalysis. Epoxides are opened by TiCE to generate cationic carbon, which is successfully trapped with bis(trimethylsilyl)propene as an aUcenylsilane (Eq. 122) [305]. Other Lewis acids, for example ZnCla, SnCU, and BF3 OEt2, proved less satisfactory. Cyclic epoxides such as cyclopentene and cyclohexene oxides gave poorer yields. An intramolecular version of this reaction proceeded differently (Eq. 123) [305]. Eqs (124) and (125) illustrate diastereoselective alkenylation and arylation of (A,0)-acetals that take advantage of the intramolecular delivery of alkenyl and aryl groups [306], Cyclic ethers... 

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