The silylalkyne-Prins cyclization: stereoselective synthesis of tetra- and pentasubstituted halodihydropyrans

[reaction: see text] A new type of Prins cyclization using silylated secondary homopropargylic alcohols and aldehydes yielding tetra- and pentasubstituted dihydropyrans is described. The presence of the trimethylsilyl group in the triple bond favors the Prins cyclization and minimizes the 2-oxonia-[3,3]-sigmatropic rearrangement as a competitive alternative pathway. Ab initio theoretical calculations of the species involved in the rearrangements support the proposed mechanism. The process is highly stereoselective, affording cis-dihydropyran as the only isomer.     

Utilization of an oxonia-Cope rearrangement as a mechanistic probe for Prins cyclizations

An oxonia-Cope rearrangement was used as an internal clock reaction to probe the mechanism of the Prins cyclization reaction and the subsequent nucleophilic capture of the resultant tetrahydropyranyl cation. The oxonia-Cope rearrangement was shown to occur rapidly under typical Prins cyclization conditions when the oxocarbenium ion resulting from the rearrangement is similar to or lower in energy than the starting oxocarbenium ion. Oxonia-Cope rearrangements can be disfavored by destabilizing the resultant oxocarbenium ion or by stabilizing an intermediate tetrahydropyranyl cation. Stereoselectivity in the nucleophilic capture was dramatically affected by the reactivity of the nucleophile and electrophile. More reactive partners combined rapidly to give axial-substituted Prins products through a least-motion pathway. High selectivity for the equatorial-substituted tetrahydropyran was observed for less reactive nucleophiles and electrophiles.     

In situ generation of 2,3-allenolates in the coupling of secondary homopropargylic alcohols and aldehydes

A study on a novel oxonia [3,3]-sigmatropic rearrangement as competitive alternative pathway to the acetylenic Prins cyclization on the addition of secondary homopropargylic alcohols to aldehydes catalyzed by iron(III) is described. ‘Ab initio’ theoretical calculations of the species involved on the rearrangement supports the in situ formation of 2,3-allenolates. The domino process involves three consecutive chemical events in one-pot format reaction (∼70% average).     

Iron(III)-catalyzed consecutive aza-Cope-Mannich cyclization: synthesis of trans-3,5-dialkyl pyrrolidines and 3,5-dialkyl-2,5-dihydro-1H-pyrroles

An efficient alkene aza-Cope-Mannich cyclization between 2-hydroxy homoallyl tosylamine and aldehydes in the presence of iron(III) salts to obtain 3-alkyl-1-tosyl pyrrolidines in good yields is described. The process is based on the consecutive generation of a γ-unsaturated iminium ion, 2-azonia-[3,3]-sigmatropic rearrangement, and further intramolecular Mannich reaction. Iron(III) salts are also shown to be excellent catalysts for the new aza-Cope-Mannich cyclization using 2-hydroxy homopropargyl tosylamine.     

Prins Cyclization Catalyzed by a FeIII/Trimethylsilyl Halide System: The Oxocarbenium Ion Pathway versus the [2+2] Cycloaddition

The different factors that control the alkene Prins cyclization catalyzed by iron(III) salts have been explored by means of a joint experimental–computational study. The iron(III) salt/trimethylsilyl halide system has proved to be an excellent promoter in the synthesis of crossed all‐cis disubstituted tetrahydropyrans, minimizing the formation of products derived from side‐chain exchange. In this iron(III)‐catalyzed Prins cyclization reaction between homoallylic alcohols and non‐activated alkenes, two mechanistic pathways can be envisaged, namely the classical oxocarbenium route and the alternative [2+2] cycloaddition‐based pathway. It is found that the [2+2] pathway is disfavored for those alcohols having non‐activated and non‐substituted alkenes. In these cases, the classical pathway, via the key oxocarbenium ion, is preferred. In addition, the final product distribution strongly depends upon the nature of the substituent adjacent to the hydroxy group in the homoallylic alcohol, which can favor or hamper a side 2‐oxonia‐Cope rearrangement.     

Gold and platinum catalyzed cascade reaction of propargyl acetates bearing terminal alkynes or methyl ketones

A gold (III)-catalyzed cascade reaction of propargyl acetates bearing an extra terminal alkyne (1) afforded γ-keto esters 3 and lactones 4. These products should be generated through allenyl ketone intermediate B via a 1,2-acyloxy cyclization/fragmentation/cycloisomerization/hydrolysis sequence. On the other hand, the cascade reaction of α-acetoxy ketones bearing terminal alkynes 5 afforded lactone 6 via allenyl ketone intermediate A. This reaction involves a [3,3]-sigmatropic acyloxy rearrangement/cycloisomerization/hydrolysis sequence.     

Electron-impact-induced 3,3-sigmatropic rearrangement and cyclization in phenyl allenylmethyl ethers

A 3,3-sigmatropic rearrangement in the M^+· of phenyl allenylmethyl ether is proposed for the observed losses of CO, C₂H₄, and CH₃. Direct cyclization in the M^+· also leads to the [M?CH₃] ion. The presence of sulfur as the heteroatom in phenyl allenylmethyl sulfide does not significantly influence the occurrence of Claisen rearrangement. Ortho interaction of the nitro group with the allenyl double bond in the side chain leads to characteristic fragment ions in 2-nitrophenyl allenylmethyl ether. Linked scans, high-resolution mass spectrometry, collision-activated dissociation-B/E linked-scan spectra, and D-labeling have been employed to support the proposed mechanisms and ion structures.     

[3,3]-Sigmatropic rearrangement of allyl and 2-butenyl 1-naphthyl sulfides

The [3,3]-sigmatropic rearrangement of alkenyl 1-naphthyl sulfides in solutions with various polarities was investigated at 138–190 °C. The reaction proceeds through the formation of 2-alkenyl-1-naphthalene thiols, which subsequently undergo cyclization to compounds of the 2,3-dihydronaphtho[1,2-b]thiophene and naphtho[1,2-b]dihydrothiopyran series. 2-Butenyl 1-naphthyl sulfide, in addition to its passing directly through a [3,3]-sigmatropic rearrangement, to a considerable extent undergoes a prior [1,3]-sigmatropic rearrangement, which ultimately leads to the formation of four cyclic products. The kinetic parameters of the rearrangement of the sulfides were determined. The more negative entropies of activation constitute evidence for the high symmetry of the transition state.Translated from Khimiya Geterotskilicheskikh Soedinenii, No. 5, pp. 611–614, May, 1981.     

Synthesis of aromatic ketones by a transition metal-catalyzed tandem sequence

Both simple Ag(I) and Au(I) are effective catalysts for a tandem [3,3]-sigmatropic rearrangement/formal Myers-Saito cyclization of propargyl esters to form aromatic ketones. A mechanism in which the metal catalyzes both of these processes through alkyne activation is proposed. By using this method a wide range of aromatic structures including naphthyl, anthracenyl and indole ketones are available from readily available propargyl esters.     

Efficient [3,3]-sigmatropic rearrangement accelerated by a trifluoroacetyl group: synthesis of benzofurans under mild conditions

The [3,3]-sigmatropic rearrangement took place smoothly during the course of trifluoroacetylation of O-phenyloxime at below room temperature to give the dihydrobenzofuran or benzofuran as a result of concomitant cyclization.     

Silver triflate and palladium acetate co-catalyzed reaction of N'-(2-alkynylbenzylidene)hydrazide with N-allyl ynamide

A silver triflate and palladium acetate co-catalyzed reaction of N'-(2-alkynylbenzylidene)hydrazide with N-allyl ynamide is described, which generates 2-amino-H-pyrazolo[5,1-a]isoquinolines in good to excellent yield. The transformation proceeds with high efficiency through 6-endo cyclization, [3 + 2] cycloaddition, 3,3-sigmatropic rearrangement, and aromatization.     

Enantioselective Claisen rearrangements with a hydrogen-bond donor catalyst

N,N'-Diphenylguanidinium ion associated with the noncoordinating BArF counterion is shown to be an effective catalyst for the [3,3]-sigmatropic rearrangement of a variety of substituted allyl vinyl ethers. Highly enantioselective catalytic Claisen rearrangements of ester-substituted allyl vinyl ethers are then documented using a new C2-symmetric guanidinium ion derivative.     

Dichloroketene-induced cyclizations of vinyl sulfilimines: application of the method in the synthesis of (+/-)-desoxyeseroline

The reactions of several aryl-, furanyl-, and vinyl-substituted sulfilimines with dichloroketene proceeded at 25 degrees C to yield thioalkyl-substituted gamma-lactams. The overall process involves nucleophilic addition of the nitrogen atom of the sulfilimine onto the highly electrophilic dichloroketene to first generate a zwitterionic intermediate. A subsequent [3,3]-sigmatropic rearrangement is followed by intramolecular trapping of the Pummerer cation by the amido anion to furnish the observed gamma-lactam product. Incorporation of donor groups on the aromatic ring of the sulfonyl functionality had little effect when aryl-substituted sulfilimines were used but exhibited a major effect on the efficiency of the reaction with furanyl-substituted systems. The placement of an electron donor group (i.e., OMe) on the sulfonyl aryl group enhances the nucleophilicity of the amido anion contained within the sulfonium ion intermediate and facilitates the rate of the 3,3-sigmatropic rearrangement. Styryl-substituted sulfilimines cyclize in a stereospecific manner and produce a 3:2-mixture of gamma-lactams and the isomeric imino-lactone system. The heavily functionalized gamma-lactams are easily converted to a variety of nitrogen containing substrates. The vinyl sulfilimine cyclization method was applied to the total synthesis of the Calabar alkaloid (+/-)-desoxyeseroline.     

Access to substituted cyclobutenes by tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition of dipropargylphosphonates under Ag/Co relay catalysis

We present herein an unconventional tandem [3,3]-sigmatropic rearrangement/[2 + 2] cycloaddition of simple dipropargylphosphonates to deliver a range of bicyclic polysubstituted cyclobutenes and cyclobutanes under Ag/Co relay catalysis. An interesting switch from allene–allene to allene–alkyne cycloaddition was observed based on the substitution of the substrates, which further diversified the range of compounds accessible from this practical method. Significantly, preliminary biological screening of these new compounds identified promising candidates as suppressors of cellular proliferation.

In situ generation of allenes through [3,3]-sigmatropic rearrangement of propargylphosphonates. Divergent allene–allene or allene–alkyne cycloaddition by Ag/Co relay catalysis. Products as promising suppressors of cellular proliferation.     

Synthesis of Phenanthrene Derivatives by Intramolecular Cyclization Utilizing the [1,2]‐Phospha‐Brook Rearrangement Catalyzed by a Brønsted Base

The synthesis of functionalized phenanthrene derivatives was achieved by intramolecular cyclization utilizing the [1,2]‐phospha‐Brook rearrangement under Brønsted base catalysis. Treatment of biaryl compounds having an α‐ketoester moiety and an alkyne moiety at the 2 and 2′ positions, respectively, with diisopropyl phosphite in the presence of a catalytic amount of phosphazene base P2‐tBu provides 9,10‐disubstituted phenanthrene derivatives in high yields. This reaction involves the generation of an ester enolate through an umpolung process, that is, addition of diisopropyl phosphite to a keto moiety followed by the [1,2]‐phospha‐Brook rearrangement, the intramolecular addition to an alkyne, and the [3,3] rearrangement of the allylic phosphate moiety in a consecutive fashion.     

Efficient synthesis of indoles using [3,3]-sigmatropic rearrangement of N-trifluoroacetyl enehydrazines

[3,3]-Sigmatropic rearrangement of N-trifluoroacetyl enehydrazines provides a novel method for the construction of indoles. N-Trifluoroacetyl enehydrazine having a cyclopentene ring smoothly underwent [3,3]-sigmatropic rearrangement followed by cyclization to give indolines in excellent yield. On the other hand, both cyclohexenyl N-trifluoroacetyl enehydrazine and acyclic N-trifluoroacetyl enehydrazine gave indoles in good yield. Additionally, the substituent effect on the benzene ring was also studied. The rearrangement of N-trifluoroacetyl enehydrazines proceeded smoothly even under either aqueous or solvent-free conditions.     

A two-component pericyclic reaction for synthesis of substituted benzofurans and aryl-quaternary carbon bonds

The reaction shown is presumed to be a new [3,3]-sigmatropic rearrangement involving an O-arylsulfoxonium species or related sulfurane. It allows a sulfoxide and a phenol to be joined and rearranged in one operation at or below room temperature, coupling an aromatic to a quaternary carbon and creating benzofurans or articulated dihydrobenzofurans in a number of examples.     

3,3]-Sigmatropic rearrangement/5-exo-dig cyclization reactions of benzyl alkynyl ethers: synthesis of substituted 2-indanones and indenes

Substituted benzyl alkynyl ethers, prepared from the corresponding α-alkoxy ketones in a two-step sequence involving enol triflate formation and KOtBu-induced E2 elimination, undergo [3,3]-sigmatropic rearrangement/intramolecular 5-exo-dig cyclization at 60 °C to form substituted 2-indanones in good overall yields. 1,3-cis-Disubstituted-2-indanones are formed preferentially when the benzylic substituent R(1) is bulky. Substituted indenes may be prepared from 2-indanones in high yields by Horner-Wadsworth-Emmons reaction.     

Synthesis of unsaturated [1,2]oxazines by using sigmatropic rearrangements and the ring-closing metathesis reaction

Various substituted unsaturated [1,2]oxazines have been synthesized by using a [2,3]- or a [3,3]-sigmatropic rearrangement and a ring-closing metathesis reaction as key steps.     

[3,3]-sigmatropic rearrangement of allyl 2-benzothienyl sulfide

Allyl 2-benzothienyl sulfide at 20–120 °C undergoes a [3,3]-sigmatropic rearrangement to give 3-allylbenzothiophene-2-thiol. The kinetic parameters of the reaction were studied. Under the experimental conditions the thiol undergoes cyclization to give 2-methyl-2,3-dihydrobenzothieno[2,3-b]thiophene, 2-methyl-benzothieno[2,3-b]thiophene, and benzothieno[2,3-b]dihydrothiopyran. Allyl 3-methyl-2-benzothienyl sulfide does not form a thiol even at 150–190 °C but rather forms only bis(3-methyl-2-benzothienyl) disulfide.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 615–618, May, 1981.