Prins reactions, 4-substituted

C-H activation at a primary benzylic site was the key step in very short syntheses of lig-nans 206 and 207 (Scheme 14.27) [138]. Even though both the substrate 203 and the vinyl-diazoacetate 204 contain very electron-rich aromatic rings, C-H activation to form 205 (43% yield and 91% ee) is still possible because the aromatic rings are sterically protected from electrophilic aromatic substitution by the carbenoid. Reduction of the ester in (S)-205 followed by global deprotection of the silyl ethers completes a highly efficient three-step asymmetric total synthesis of (-i-)-imperanene 206. Treatment of (R)-205 in a more elaborate synthetic sequence of a cascade Prins reaction/electrophilic substitution/lacto-nization results in the total synthesis of a related lignan, (-)-a-conidendrin 207. 

Simple mono- and disubstituted alkenes react to yield 1,3-diols, when the Prins reaction is carried out at elevated temperature. Diols originate from the attack of water on carbocation 18, or through the acidolysis of dioxanes under the reaction conditions. When the reaction is conducted in acetic acid, monoacetates are formed by acetate attack on 18. Dienes resulting from the dehydration of intermediate diols are the products of the transformation of more substituted alkenes. Monoacetates and diols may react further to yield 1,3-diol diacetates. When the Prins reaction... 

Dioxacyclohexanes can be produced in excellent yields from aliphatic or aryl-substituted alkenes.64 Dilute sulfuric acid at or above room temperature with paraformaldehyde appears to give the best results. Dioxane-water or acetic acid as solvent was found to afford increased yields in the Prins reaction of arylalkenes. 

The stereochemistry of the Prins reaction is complex. In the transformation of cyclohexene and 2-butenes anti stereoselective addition was observed,67-69 whereas syn addition of two formaldehyde units takes place in the formation of 1,3-dioxanes from substituted styrenes.70 Most of the transformations are, however, nonstereo-selective,71 72 accounted for by carbocation 18. 

Few examples of the Prins reaction of homologous aldehydes and ketones are known.73,74 Acetaldehyde was shown to react smoothly with isobutylene under mild conditions, whereas other, less substituted alkenes were found to be very unreactive.73... 

Triflic acid has been successfully used in the stereocontrolled synthesis of substituted tetrahydropyrans. 2,4,6-Trisubstituted tetrahydropyrans have been synthesized by an intramolecular Prins reaction-pinacol sequence694 [Eq. (5.250)]. 

Spirocyclic 4-substituted tetrahydropyrans are readily obtained through the Prins reaction involving cyclic ketones, homoallylic alcohols and MeS03H <02H(58)659>. The cationic species generated when alkyne-Co complexes derived from 8-valerolactone are treated with SnCl4 undergo a double cyclisation to yield the oxaspiro[5.5]undecane <02T2755>. 

Substituted versions of these reagents retain the symmetry of 40 and 47. One interesting type is prepared by a Prins reaction of the diketone 51 with trioxan 52, the trimer of formaldehyde.6 The six- 54 and seven-membered 55 compounds are easily made in the same way. 

Aliphatic homoallyl mercaptans and aldehydes yield trisubstituted tetrahydrothiopyrans with good diastereoselectivity through an InCb-mediated Prins reaction. Similar selectivity is observed with l-phenyl-3-butene-l-thiol and benzaldehyde scrambling is noted with substituted benzaldehydes (Scheme 41) <01JOC739>. 

The process from the FMC company involves as the pivotal step an intramolecular stereoselective [2 + 1 [-cycloaddition. In a Prins reaction [94] of chloral and isobutene, followed by an isomerisation, a racemic, trichloromethyl-substituted aUyl alcohol is obtained. Reaction with the isocyanate from (R)-naphthylethyl-amine enables separation ofthe diastereomers by crystallisation. The carbamate is cleaved by trichlorosilane/triethylamine, thus permitting the recycling of the chiral auxiliary. The optically pure (R)-aUyl alcohol is reacted with diketene, to produce the / -keto-ester. After diazo transfer and basic cleavage, the diazoacetate is obtained catalysed by a copper salt, this is converted in a [2 + 1 ]-cyclo-addition into a bicyclic lactone. The Boord reaction (discovered by Cecil E. Boord in 1930) [95] finally gives (IR)-cis-permethric acid. [96]... 

The acid-promoted Prins reaction between a homoaUyhc alcohol and an aldehyde is a weU-estabhshed synthesis of tetrahydropyrans (Scheme 4) [ 14,15]. While substituted tetrahydropyrans are often assembled by cyclizations forming a C - O bond, the Prins reaction undergoes cyclization by C - C bond formation. The Prins reaction of the silyl-modified substrates [16], which can be regarded as the intramolecular Hosomi-Sakurai reaction, is effectively activated by the allylsilane unit. The stereochemistry of the 2,6-cfs-form produced in the case of the exo-allylsilane unit is elucidated by the 6-membered transition state model, hi the cyclization of the ewdo-aUylsilane substrates, since the silyl group would be fixed on the axial position of the 6-membered transition states, the tetrahydropyrans with both 2,6-cis and fraws-forms can be synthesized (Panek Sect. 3.3.9). This type of cychzation was also... 

The Prins reaction of a tenfold or larger excess of formaldehyde with 1-substituted 4-phenyl-l,2,3,6-tetrahydropyridines gives the bicyclic compound (42), 2 which exists in the 0-inside conformation as previous work had suggested should be the case. 

Olefin migration Oxidation of alcohols Passerini reaction Pauson-Khand reaction Pinacol cross-coupling Pinner reaction Polymerization of olefins Prins reaction Propargylation Radical addition Radical cyclization Radical substitution Reduction... 

The Prins reaction is one of the way to create one-step processes for obtaining derivatives of P-substituted hydrogenated flirans with good... 

It was shown that 3-alkyl-substituted and 2,3,5-trialkylsubstituted-2,5-dihydroflirans, 4-alkyl-substituted tetrahydrofuranols-3 can be obtained by Prins reaction in trifluoroacetic acid [2-8],... 

In the sphere of mathematical and quantum chemistry the work examines regularities of synthesis of substituted 1,3-dioxins as a result of the Prins reaction. 

Cyclization, which shows a close relationship to the Prins reaction, is expected to give rise to the substituted pyrans 228 with high stereospecificity, depending on the configuration of the double bond. 

Parchinsky et al. (2011) reported synthesis of symmetrically and unsymmetrically substituted chiral, racemic 1-azaadamantanes via BF3.0Et2-promoted aza-Prins reaction under microwave irradiation. Reaction of ( )-[(4-methylcyclohex-3-en-l-yl) methyljamine with an equimolar amount of an aldehyde in the presence of 1.0 equiv. of Bp3.0Et2 at ISO C for 1 h gives predominantly bicyclic piperidines whereas in presence of excess amount of the aldehydes, symmetrically substituted 1-azaadamantanes are the major products. The yield of the products ranges from 52-83%. 

The synthesis of different substituted finans by cyclization of 4-pentynones using potassium tert-butoxide in DMF was reported <96TL3387>. Dihydrofuran 32 can be prepared by a destannylative acylation of l-[(2-methoxyethoxy)methoxy]-2-(phenylsulfonyl)-2-(tributylstannyl)-cyclopropane. Treatment of 32 with BFj-EtjO yields 3-acyUurans via an intramolecular Prins-type reaction of the resulting oxonium ion intermediate <96TL4585>. 

The scheme below depicts the novel use of a carbonyl ene cyclization (A, Lewis acid-catalyzed) and a closely related Prins cyclization (B, Brpnsted acid-catalyzed) to generate predominantly trans (cyclization condition A) or cis (cyclization condition B), di and tri substituted piperidines 160 and 161 <06JOC2460 06OBC51>. Of note, in the formation of di-substituted derivatives, R1 = H and R2 = Ph, no reaction occurs under cyclization condition B and the cis isomer 160 is obtained exclusively under cyclization condition A. In the case of tri-substituted derivatives, when bulky substituents at the 2-position (R1 = f-Bu or Ph) are present the trans diastereomer 161 is obtained almost exclusively under cyclization condition A, while no diastereoselectivity is seen under cyclization condition B. 

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