Iron(III)-catalyzed Prins-type cyclization using homopropargylic alcohol: a method for the synthesis of 2-alkyl-4-halo-5,6-dihydro-2H-pyrans

[reaction: see text] A new Prins-type cyclization between homopropargylic alcohol and aldehydes in the presence of FeX(3) to obtain 2-alkyl-4-halo-5,6-dihydro-2H-pyrans in good yield is described. Osmium-catalyzed cis dihydroxylation provided direct access to trans-2-alkyl-3-hydroxy-tetrahydro-pyran-4-ones. Anhydrous ferric halides are also shown to be excellent catalysts for the standard Prins cyclization using homoallylic alcohol. Isolation of an intermediate acetal provides substantiation of a proposed mechanism.     

ZrCl4 mediated cyclization between epoxides and homopropargylic alcohols: synthesis of 4-chloro-5,6-dihydro-2H-pyran derivatives

Epoxides undergo cyclization with homopropargylic alcohols in the presence of zirconium tetrachloride under mild conditions to afford the corresponding dihydropyran derivatives in excellent yields under mild conditions.     

TMSI mediated Prins-type cyclization of ketones with homoallylic and homopropargylic alcohol: synthesis of 2,2-disubstituted-, spirocyclic-4-iodo-tetrahydropyrans and 5,6-dihydro-2H-pyrans

The Prins-type cyclization of ketones with homoallylic and homopropargylic alcohols in the presence of TMSI generated in situ from TMSCl and NaI produced 2,2-disubstituted- or spirocyclic-4-iodo-tetrahydropyrans and spirocyclic-4-iodo-5,6-dihydro-2H-pyrans in good yields. These iodopyrans are reported for the first time.     

Chemoenzymatic synthesis of optically active heterocyclic homoallylic and homopropargylic alcohols

A chemoenzymatic methodology has been developed using indium-mediated allylation of heterocyclic aldehydes under aqueous conditions followed by Pseudomonas cepacia lipase-catalyzed enantioselective acylation of racemic homoallylic and homopropargylic alcohols in organic media. It is observed that the lipase immobilized on ceramic particles (PS-C Amano II) catalyzes the resolution in a highly enantioselective manner in less time as compared to the native enzyme (PS Amano). The approach provides new functionalized chiral synthons useful in the synthesis of natural and pseudonatural products.     

Regiospecific synthesis of 2-substituted 4-methyl-3,6-dihydro-2H-pyrans

The chloroalkylation of 3-halo-2-methyl-1-buten-4-ols was used to synthesize 4,5-dihalo-4-methyl-2-substituted tetrahydropyrans, which were converted regiospecifically to 3,6-dihydropyrans by reaction with magnesium. A similar reaction with zinc dust gave mixtures of 3,6- and 5,6-dihydropyrans.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 9, pp. 1189–1193, September, 1985.     

Reaction of 5,5-dialkyl-2-halo-6-hydroxy-5,6-dihydro-1H-pyridine-3,4,4-tricarbonitriles with alcohols

Russian Journal of Organic Chemistry -     

Asymmetric synthesis of 2-aryl-2,3-dihydro-4-quinolones via bifunctional thiourea-mediated intramolecular cyclization

A novel asymmetric preparation of optically enriched 2-aryl-2,3-dihydroquinolin-4(1H)-ones has been developed. By installing a sulfonyl group on the nitrogen of the anilines and an ester function on the unsaturated ketones, an intramolecular organocatalytic cyclization took place readily in a stereoselective manner, resulting in the formation of dihydroquinolones with high enantioselectivity.     

Chemical properties of 3,6- and 5,6-dihydro-2H-pyrans (review)

The reactions of 3,6- and 5,6-dihydro-2H-pyrans that are due to the presence of double and ether bonds are correlated.Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 24, No. 3, pp. 291–304, March, 1988.     

Novel tunable CuX(2)-mediated cyclization reaction of cyclopropylideneacetic acids and esters for the facile synthesis of 4-halomethyl-2(5H)-furanones and 4-halo-5,6-dihydro-2H-pyran-2-ones

[reaction: see text] A mixture of cyclopropylideneacetic acids (or esters) and CuBr(2) (or CuI/I(2)) in aqueous acetonitrile afforded 4-substituted 2(5H)-furanones or 3,4-substituted 5,6-dihydro-2H-pyran-2-ones in moderate to good yields. The selectivity of the reaction greatly depended on the reaction temperature.     

Vilsmeier-Haack reactions of 2-arylamino-3-acetyl-5,6-dihydro-4H-pyrans toward the synthesis of highly substituted pyridin-2(1H)-ones

A facile and efficient one-pot synthesis of highly substituted pyridin-2(1H)-ones was developed via Vilsmeier-Haack reactions of readily available enaminones, 2-arylamino-3-acetyl-5,6-dihydro-4H-pyrans, and a mechanism involving sequential ring-opening, haloformylation, and intramolecular nucleophilic cyclization reactions is proposed.     

Stereoselective synthesis of allylic sulfones via the oxonia-Cope rearrangement of homoallylic alcohols containing a homoallylic sulfone moiety

The homoallylic alcohols 3 that can be prepared by the indium-mediated addition of haloallylic sulfones 1 to aldehydes 2 undergo the oxonia-Cope rearrangement with aldehydes 2 to give rise to the allylic sulfones 4 containing a conjugated diene moiety in a highly stereoselective manner. Electron-rich aldehydes preferentially participate in this oxonia-Cope rearrangement with the homoallylic alcohols 3. Excellent correlations of the stereochemistry (anti-3 to trans-allylic sulfone 4 and syn-3 to cis-allylic sulfone 4) have been observed in the oxonia-Cope rearrangement.     

Hetero-Diels-Alder reactions of alpha-aryl-beta-monohalo-alpha-nitrosoethylenes: diastereoselective synthesis of 6-substituted 3-aryl-4-halo-5,6-dihydro-4H-1,2-oxazines.

Treatment of alpha-aryl-beta-bromo(or chloro)-alpha-nitrosoethylene, prepared in situ from alpha-monobromo(or chloro)ketoximes and sodium carbonate in ether at rt, with allytrimethylsilane afforded exclusively trans-(4S,6S)- and trans-(4R,6R)-3-aryl-4-halo-6-[(trimethylsilyl)methyl]-5,6-dihydro-4H-1,2-oxazines 10 albeit in low yields. Similar treatment of beta-halo-alpha-nitrosoethylenes with ethyl vinyl ether, however, gave single stereoisomers, i.e., cis-(4S,6S)- and cis-(4R,6R)-6-ethoxy-4-halo-5,6-dihydro-4H-1,2-oxazines 11, in moderate to good yields. The result is in contrast to the reported predominant formation of trans-11a by a radical reaction. On the other hand, similar reactions with tert-butyl vinyl ether at 30 degrees C gave diastereomeric mixtures of cis-(4S,6S)-, cis-(4R,6R)-, trans-(4S,6R)-, and trans-(4R,6S)-6-(tert-butoxy)-4-halo-5,6-dihydro-4H-1,2-oxazines 12. In contrast to compounds 11, the major isomers have (4S,6R) and (4R,6S) configurations. The tendency of a [4 + 2] cycloaddition reaction is consistent with that observed in the Diels-Alder reaction with inverse-electron demand. The stereochemistries of compounds 10-12 were assigned on the basis of the (1)H NMR coupling constants, which were unambiguously determined by the decoupling experiments. All reactions leading to compounds 10-12 proceed with very high regioselectivity. Diastereoselectivity and high regioselectivity are understood in terms of the frontier orbital method. It has been found that cis-12g is isomerized to a mixture of stereoisomers in favor of the trans-isomer in the presence of HClO(4) (72%) in CHCl(3) at rt.     

Efficient synthesis of 4-(2'-alkenyl)-2,5-dihydrofurans and 5,6-dihydro-2H-pyrans via the Pd-catalyzed cyclizative coupling reaction of 2,3- or 3,4-allenols with allylic halides

In the absence of a base, palladium(II) catalysts, such as PdCl(2), PdCl(2)(CH(3)CN)(2), Pd(OAc)(2), and [(pi-C(3)H(5))PdCl](2), can catalyze the cyclizative coupling reaction of 2,3- or 3,4-allenols with allylic halides in DMA at room temperature to provide 2,5-dihydrofurans and 5,6-dihydro-2H-pyrans, respectively, in moderate to good yields. Under similar reaction conditions, nonsubstituted 2,3-allenol 1s affords bimolecular cyclizative coupling product 5s as the major product. The scope of the reaction and its mechanism have been studied briefly. On the basis of the experimental results, the transformation was believed to proceed via a divalent palladium-catalyzed pathway.     

Synthesis of 2-amino-5,6-dihydro-4H-1,3-thiazines and related compounds by acid catalyzed cyclization of allylic isothiuronium salts

Several allylic isothiuronium salts 6 have been shown to yield 4-substituted 2-amino-5,6-dihydro-4H-1,3-thiazines ( 2 ; R³ = H) and the 2-phenylimino compound 10 on exposure to trifluoroacetic acid or trifluoroacetic acid-stannic chloride. The overall process constitutes a convenient transformation of readily available ketones or aldehydes 3 into the target hetero-cycles. The scope and limitations of this approach are discussed in terms of carbenium ion intermediates ( 7 ). Whereas this method successfully led to the imidazo[2,l-b][1,3]thiazine 13 (93% from 12 ), its application to the synthesis of 2-amino-2-thiazolines (eg. 14 → 15 ) or imidazo-[2,1-b]thiazoles (eg. 16 → 17 ) was unsuccessful. The 2-acetylimino derivatives 9 were found to be useful for purification of the 2-aminothiazines.     

Synthesis of 4-halotetrahydropyrans from allylsilanes and carbonyl compounds in the presence of lewis acids

An unexpected behavior of the reaction of allylsilanes and carbonylcompounds allowed the stereospecific preparation of differently substituted 4-halotetrahydropyrans with an “all cis” configuration.     

Scandium(III) triflate-TMSCl promoted cyclization of aziridin-1-yl oximes to 5,6-dihydro-4H-[1,2,4]oxadiazines

A convenient and facile one-pot synthesis of 5,6-dihydro-4H-[1,2,4]oxadiazine is described. Treatment of aziridin-1-yl-oximes with Scandium(III) triflate readily afforded 5,6-dihydro-4H-[1,2,4]oxadiazine in the presence of chlorotrimethylsilane.     

One-pot synthesis of aromatic homoallylic alcohols from aldehydes and Grignard reagents promoted by Titanium(IV) tetraisopropanolate

An efficient method of Titanium(IV) mediated one-pot reaction approaching aromatic homoallylic alcohols from aldehydes and dual Grignard reagents was developed with good isolated yields. This method could use aromatic-, heteroaromatic-, or aliphatic-aldehydes as starting materials. However, electron-riched benzaldehyde or cinnamaldehyde tended to precede further hydroxyl eliminations to give all conjugated structures as demonstrated.     

Synthesis of 2H-indazoles via Lewis acid promoted cyclization of 2-(phenylazo)benzonitriles

Lewis-acid promoted "coarctate" cyclization of 10 2-(phenylazo)benzonitrile derivatives furnishes the isoindazole ring system in ca. 65-95% yield. A plausible mechanism for this unusual transformation is proposed.     

Total synthesis of ionophores the monensin BC-rings via permanganate promoted stereospecific oxidative cyclization

Complex tetrahydrofuran 8, containing the elements of the BC-rings of monensin with four chiral centers, and functionalized for further elaboration, is synthesized via permanganate promoted stereospecific oxidative cyclization of an acyclic, achiral 1,5-diene precursor.