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.     

Chiral Acylsilanes in Organic Synthesis. Part 3. Silicon-directed stereoselective preparation and Ireland ester-enolate rearrangement of O-acyl-substituted α-silylated allyl alcohols

Stereocontrolled addition of alk-1-enylmetal reagents to the chiral (alkoxymethyl)-substituted acylsilanes (±)- 6 gave rise to α-silylated allyl alcohols, which were converted to the corresponding acetates or propionates 11–16 (Scheme 2). Deprotonation and silylation with Me₃SiCl afforded – in an Ireland ester-enolate-accelerated Claisen rearrangement – stereoselectively αδ-silylated γδ-unsaturated carboxylic acids 18–24 (Scheme 4). The Me₃Si groups in α-position to the COOH group of these compounds were removed chemoselectively in presence of the chiral silyl group in δ-position by treatment with Bu₄NF · 3 H₂O or Et₃N · 3 HF (→ 27–32 ; Scheme 5). The reaction sequence allows a novel stereocontrolled access to chiral C-frameworks possessing a vinylsilane moiety with its full reaction potential.     

Enantioselective Catalytic Aldehyde α-Alkylation/Semipinacol Rearrangement: Construction of α-Quaternary-δ-Carbonyl Cycloketones and Total Synthesis of (+)-Cerapicol

An enantioselective aldehyde α-alkylation/semipinacol rearrangement was achieved through organo-SOMO catalysis. The catalytically generated enamine radical cation serves as a carbon radical electrophile that can stereoselectively add to the alkene of an allylic alcohol and initiate ensuing ring-expansion of cyclopropanol or cyclobutanol. This tandem reaction enables the production of a wide range of nonracemic functionalizable α-quaternary-δ-carbonyl cycloketones in high yields and excellent enantioselectivity from simple aldehydes and allylic alcohols. As a key step, the intramolecular reaction was also successfully applied in the asymmetric total synthesis of (+)-cerapicol.     

Enantioselective Catalytic Aldehyde α‐Alkylation/Semipinacol Rearrangement: Construction of α‐Quaternary‐δ‐Carbonyl Cycloketones and Total Synthesis of (+)‐Cerapicol

An enantioselective aldehyde α‐alkylation/semipinacol rearrangement was achieved through organo‐SOMO catalysis. The catalytically generated enamine radical cation serves as a carbon radical electrophile that can stereoselectively add to the alkene of an allylic alcohol and initiate ensuing ring‐expansion of cyclopropanol or cyclobutanol. This tandem reaction enables the production of a wide range of nonracemic functionalizable α‐quaternary‐δ‐carbonyl cycloketones in high yields and excellent enantioselectivity from simple aldehydes and allylic alcohols. As a key step, the intramolecular reaction was also successfully applied in the asymmetric total synthesis of (+)‐cerapicol.     

Synthesis and thermal rearrangement of allylic 3,5,6-trimethyl-2-pyrazinylacetates: A heterocyclic carroll rearrangement

The synthesis of allylic 3,5,6-trimethyl-2-pyrazinylacetates 2–4 has been achieved by the reaction of 3,5,6-trimethyl-2-pyrazinylacetic acid lithium salt ( 1 ) with phenyl dichlorophosphate followed by addition of the allylic alcohol. On thermolysis, the allylic β-heteroaromatic esters underwent a rearrangement, analogous to the Carroll rearrangement, to generate the corresponding γ,δ-unsaturated heteroaromatic compound. The configuration of the double bond formed in the product was the E-isomer. The rate of the rearrangement was dependent on the substitution pattern of the allylic portion of the molecule with 4>2>3 . The ester enolate version of the heterocyclic Carroll rearrangement was investigated with 2 , however these conditions did not promote the rearrangement.     

Nachweis von π → σ-Umlagerungen bei Ligandenverdrängungsreaktionen von π-Allyl-π-cyclopentadienyl-Palladiumkomplexen

It has been proved by NMR. measurements at low temperatures that the ligand displacement reactions of (π-all)Pd(π-C₅H₅) and Lewis bases L yielding PdL₄ proceed by a π → σ rearrangement of the allylic group as the primary step. The organic reaction product is the 1-isomer of the corresponding allylcyclopentadiene but in the reactions of (π-1,1,2-Me₃C₃H₂)Pd(π-C₅H₅) with L besides the isomeric allylcyclopentadienes also 2,3-dimethylbutadiene and cyclopentadiene are formed. The reaction mechanism will be discussed.     

Heterocyclic N-glycosides. VIII. Anomerisation and rearrangement of 2′,3′-unsaturated N-glycosides

The acid catalyzed transformation of cither 1-(4 -O-acety1-2,3 -dideoxy-α- or β-L-glycero-pent-2 -cnosyl)-5,6-dichlorobenzotriazole gave the same mixture of unsaturuted glycosides. The main three components of this mixture were the above α and β anomers and a glycal-type compound which results from the allylic rearrangement of the 5,6-dichlorobenzotriuzole moiety to the C-3 position of the carbohydrate. Evidence is presented that these results can be rationalized as proceeding through an allylic carbonium ion. Preliminary experiments on transglycosidation reactions using 2′,3′-unsaturated N-glycosides are reported.     

Thermolysis of N-allylic 1,2,4-triazoles

A number of 4-allylic substituted 3,5-diphenyl-4H-1,2,4-triazoles were thermolyzed at 315–320° in evacuated glass ampoules. The main reaction in the melt was rearrangement to the corresponding 1-substituted triazoles, which appeared to proceed via competing S_N2 and S_N2′ mechanisms. The allylic systems were observed to undergo [2,3]-allyl walk reactions between the 1- and 2-ring positions. Allyl to vinyl isomerization also took place. Substitution of the allylic moiety increased the rate of reaction but decreased the rate of isomerization of allylic to the vinylic substituted triazoles. The 4-vinyl substituted triazoles were inert under the reaction conditions. Some triazoles were converted into substituted pyridines. This was proposed to proceed via nitrogen extrusion and formation of a 1,3-dipolar intermediate (nitrile ylide) which added intramolecularly to the allyl moiety and subsequently aromatized to the pyridine.     

Synthesis and Rearrangement of Silylated Oxy-Cope Systems

Addition of allyl or vinyl organometallic reagents to chiral a,b\alpha,\beta- or b,g\beta,\gamma -unsaturated acylsilanes afforded stereoselectively 3-silylated 3-hydroxy-1,5-dienes that are stereoselectively converted to d,e\delta,\varepsilon-unsaturated acylsilanes by the thermal oxy-Cope rearrangement. The rearrangement is restricted to compounds possessing an (alkoxy)methyl substituent at the silicon moiety; upon heating, analogous compounds with the t-BuMe₂_2Si group in the 3-position led to decomposition only. The (alkoxy)methyl group at silicon is supposed to act as a weak internal base, which accelerates the rearrangment reaction.     

Investigation of the Chemo- and Stereoselectivity of the Ketene-Claisen Rearrangement

A novel type of ketene-Claisen rearrangement in which the precursor of the rearrangement is generated in situ by reaction of optically active allyl thioethers with dichloroketene is described. A characteristic feature of this rearrangement is the excellent chemoselectivity in favor of allyl thioethers vs. allyl ethers, i.e., exclusive chirality transfer of the allylic sulfur moiety is observed with 12, 13 , and 25--27 . The cyclic, optically active allyl thioethers (+)-(R)- 4 and (?)-(S)- 4 and the open-chain allyl thioethers 11--13 rearrange with in situ generated dichloroketene to the optically active thioesters (?)-(S)- 28 , (+)-(R)- 28 , and 31-33 , respectively. A chirality-transfer of > 99% in the cyclic cases (+)-(R)- 4 and (?)-(S)- 4 , and 96--98 % in the open-chain cases 11--13 is observed. Furthermore, the dichloroketene-Claisen rearrangement is characterized by a high asymmetric 1,2-induction. The chiral allylic sulfides 25--27 give the optically active thioesters 36--38 with a 1,2-induction > 99% as determined by NMR-shift experiments.     

Copper mediated defluorinative allylic alkylation of difluorohomoallyl alcohol derivatives directed to an efficient synthetic method for (Z)-fluoroalkene dipeptide isosteres

Difluoroallylation of optically pure O-silylated (S)-2-methyl-3-hydroxypropanal 10a with bromodifluoropropene mediated by indium provided the corresponding difluorohomoallyl alcohol 11a with low diastereoselectivity, but without a decrease in optical purity. Defluorinative allylic alkylation of each diastereomer of the difluorohomoallyl alcohol efficiently proceeded by the reaction with trialkylaluminium and Cu(I) system or Grignard reagent and a catalytic amount of CuI system in THF to give the fluorine-substituted allylic alcohol 12 in an high yield and in an excellent Z selective manner. Subsequent imidate Claisen rearrangement of the allylic alcohol 12 proceeded with a complete 1,3-chirality transfer to give the fluoroalkene dipeptide isostere structure 14 after the final conversion of the primary alcohol 20 into the carboxylic acid form.     

Synthesis and Rearrangement of Silylated Oxy-Cope Systems

Addition of allyl or vinyl organometallic reagents to chiral a,b\alpha,\beta- or b,g\beta,\gamma -unsaturated acylsilanes afforded stereoselectively 3-silylated 3-hydroxy-1,5-dienes that are stereoselectively converted to d,e\delta,\varepsilon-unsaturated acylsilanes by the thermal oxy-Cope rearrangement. The rearrangement is restricted to compounds possessing an (alkoxy)methyl substituent at the silicon moiety; upon heating, analogous compounds with the t-BuMe₂_2Si group in the 3-position led to decomposition only. The (alkoxy)methyl group at silicon is supposed to act as a weak internal base, which accelerates the rearrangment reaction.     

Some Aspects of the Chemistry of Nitro Compounds

The present brief account relates our discovery of new reactions revolving around the chemistry of the NO₂ group. It covers the condensation of MeNO₂ with hindered ketones, and the synthesis of pyrroles, triazoles, and enamides. It also describes new transformations of allylic nitro compounds, such as their conversion to allylic sulfones and unsaturated lactones, their sigmatropic rearrangement into allylic nitrites and thence into allylic alcohols, as well as their use in a short synthesis of nitroestrone derivatives. This is followed by an unusual reduction method furnishing unsubstituted amines (RR′C?NH) under conditions where these hydrolytically labile species can be captured inter‐ or intramolecularly. Finally, a mechanistic study of a strange alkyne‐forming reaction, first reported by Abidi and later shown by Corey and co‐workers to proceed through allylic nitro intermediates, ultimately led to a practical and powerful synthesis of alkynes starting from β‐keto esters.     

A PhSeCl-mediated allylic oxidation of prenyl moiety: a convenient method for the construction of 3-isopenten-2-ol unit

A phenylselenenyl chloride (PhSeCl)-mediated allylic oxidation to give allylically rearranged alcohol has been developed. A possible mechanism for the present reaction is generation of allylic selenide from prenyl moiety via [1,3]-sigmatropic rearrangement, followed by oxidation and [2,3]-sigmatropic rearrangement to afford 3-isopenten-2-ol.     

α-methoxyallyl sulfides as a novel homoenolate dianion equivalent

α-Methoxyallyl sulfides 1 proved to serve a novel homoenolate dianion equivalent. Introduction of two electrophiles into 1 was realized by successive regiospecific reaction of an allylic moiety with electrophiles intervened by an acid-catalyzed thioallylic rearrangement. Facile desulfurization of the products under mild conditions afforded a variety of (α,β- unsaturated carbonyl compounds and 2,3,4-trisubstituted furans.     

Facile Synthesis,Characterization, and Fluorescence Studies of Novel Porphyrin Appended Thiazoles

A facile and high yielding synthesis of porphyrin appended thiazoles 5 from the reaction of 5‐(4‐thiocarboxamidophenyl)‐10,15,20‐triphenylporphyrin with α‐bromo ketones has been described. The fluorescence studies of synthesized porphyrin appended thiazoles 5 in chloroform indicate that porphyrin π system is not greatly perturbed by substitution of a thiazole moiety at meso‐phenyl ring even in the excited state.     

Nucleophilic Substitution in the Allylic System of Codeine and Pseudocodeine: Reactions with lithium cyano(methyl)-and (aryl)cyanocuprates. Crystal and molecular structure of 8α-phenyl-6,7-didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan and 6α-phenyl-7,8-didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan

Nucleophilic substitution of 6β-chloro-7,8-didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan ( 1 ) and 8α-bromo-6,7-didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan ( 2 ) with lithium cyano(methyl)- and (aryl)cyanocuprates(I) ( 5a–c ) was accompanied by allylic rearrangement with both change and retention of orientation of the substituting group (Scheme 1, Table 1). Nucleophilic substitution in 7,8-didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6α-yl methanesulfonate ( 3 ) and 7,8-didehydro-4,5α-epoxy-3-methoxy-17-methylmorphinan-6β-yl methanesulfonate ( 4 ) proceeded without allylic rearrangement with both change and retention of the orientation of the substituting group (Scheme 2, Table 1). X-Ray diffraction studies of the products 6,7-didehydro-4,5α-epoxy-3-methoxy-17-methyl-8α-phenylmorphinan ( 6b ) and 7,8-didehydro-4,5α-epoxy-3-methoxy-17-methyl-6β-phenylmorphinan ( 7b ) were carried out (Figs. 1 and 2).     

A One‐Pot Cross‐Pinacol Coupling/Rearrangement Procedure

A new catalytic retro‐pinacol/cross‐pinacol reaction, followed by subsequent rearrangement or deoxygenation of the intermediately formed vicinal diols, is described. This operationally simple one‐pot protocol allows isolation of geminal α,α‐diphenyl ketones or 1,1‐diphenyl alkenes with high yields and selectivities.     

Desymmetrization of N‐Sulfonated Aziridines by Alkyllithium Reagents in the Presence of Chiral Ligands

The stereochemical course of the rearrangement of the N‐sulfonylaziridines 5, 15 , and 25 in the presence of s‐BuLi/(?)‐sparteine to the bicyclic sulfonamides 4, 16 , and 17 , respectively, has been investigated chemically and by X‐ray structure analysis. The absolute configurations of the products were, in all cases, opposite to those of the alcohols formed upon rearrangement of the corresponding epoxides. Similarily, the allylic sulfonamide 10 , resulting from rearrangement of 7‐[(4‐methylphenyl)sulfonyl]‐7‐azabicyclo[4.1.0]heptane ( 7 ) under the same reaction conditions, had the (R)‐configuration, while cyclohexen‐3‐ol, obtained upon rearrangement of cyclohexene oxide, is known to be (S)‐configured. Deuterium labelling showed that the rearrangement of 7 proceeds via enantioselective α‐elimination to a carbene, which undergoes a 1,2‐H shift.     

Efficient Synthesis of Methyl 2-(tert-Butyl)acrylate and Analogous Esters

The title products are prepared via an efficient three-step synthesis which involves hydroalumination of methyl propiolate and Lewis-acid-promoted reaction with acetone in the presence of BF₃ followed by two highly selective S_N2′ reactions. The key step is the reaction of 2-(chloromethyl)acrylates with R₂CuLi/ZnCl₂ reagents which takes place with complete allylic rearrangement.