Completely stereospecific 1,2-migration of alkyl groups in Et2AlCl promoted pinacol-type rearrangement

Completely stereospecific 1,2-migration of alkyl groups was achieved in Et₂AlCl promoted pinacol-type rearrangement of chiral β-mesyloxy alcohols to give optically pure α-alkyl ketones including both enantiomers of 4-methyl-3-hexanone, an alarm pheromone of ant.     

Synthese et transposition thermique d'alcools α-ethyleniques β'-alleniques

Thirteen variously substituted α-ethylenic β'-allenic alcohols (1,5,6-triene-3-ols) have been synthesized by three different methods, for two of which the key step was the reaction of an organo copper reagent with a derivative of a β-hydroxy γ-ethylenic alcohol (1-ene-5-yne-3,7-diol). The[3,3]-sigmatropic rearrangement of these alcohols, following the heating of their solution in diglyme, leads to γ-dienic aldehydes and ketones. The yields are best (60–70%) for tertiary alcohols substituted on carbon 5. Comparisons of the reactivities of these 13 alcohols show that the mechanism of this rearrangement can probably vary, following the substitution from a cyclohexadiyl biradical process to a concerted pathway involving a cyclohexane transition state.     

Chemistry of 1,4-dioxene II : A new method for the two-carbon homologation of aldehydes and ketones to α-hydroxymethyl ketones

1,4-Dioxen-2-yl lithium $\text{2}$ reacts with ketones or aldehydes to give alcohols $\text{3}$ which lead after an allylic rearrangement under mild conditions, followed by reduction and hydrolysis to α-hydroxymethyl ketones in fair yields.     

The Economic Synthesis of Pyridinium Fluorochromate(VI), C5H5NH[CrO3F] (PFC), and Solvent‐Free Oxidation of Organic Substrates with PFC

Abstract

A 1:1:1 stoichiometric reaction among CrO₃, aqueous HF and pyridine affords orange crystalline pyridinium fluorochromate(VI), C₅H₅NH[CrO₃F] (PFC), in 99.2% isolated yield. The reagent under solvent‐free conditions readily converts benzylic, secondary, and allylic alcohols to the corresponding carbonyls and selectively oxidizes secondary alcohols in the presence of primary alcohols, polycyclic hydrocarbons to cyclic ketones, benzoin to benzil, PPh₃ to O?PPh₃, methylphenyl sulfide to sulfoxide, cyclohexanone oxime to cyclohexanone, an allylic Δ⁵‐steroid to the corresponding α,β‐unsaturated ketone and deprotects dioxolanes and dithiolanes to aldehydes; the economic synthesis of PFC, its ease of reaction without solvent, versatility, and high isolated yields of the products are the significant features of the protocol.     

Asymmetric transfer hydrogenation of α,β-unsaturated, α-tosyloxy and α-substituted ketones

Asymmetric transfer hydrogenation of cyclic and acyclic α,β-unsaturated ketones catalysed by η⁶-p-cymene/ruthenium(II) and η⁵-pentamethylcyclopentadienyl/rhodium(III) complexes have been investigated. Cyclic α,β-unsaturated ketones appeared to be more suitable substrates for the synthesis of enantiomerically pure allylic alcohols than do acyclic α,β-unsaturated ketones. A proposed mechanism for the formation of 4-phenyl-[1,3]-dioxolan-2-one from α-tosyloxy- and halo-substituted acetophenones is discussed. The results of further investigations into the reduction of a range of α-tosyloxyacetophenones and the dynamic kinetic resolution of α-substituted ketones is presented.     

Modified Borohydride Agents1a-d Methyltriphenylphosphonium Tetrahydroborate; MePh3P+BH4 − as a Selective and An Efficient Reducing Agent

Abstract

MePh₃P⁺BH₄ ^? is able to reduce aldehydes and ketones to their corresponding alcohols in CH₂Cl₂. Aldehydes are reduced with high selectivity in the presence of ketones. α,β-Unsaturated carbonyl compounds undergo 1,2-reduction and produce their corresponding allylic alcohols in high yields. Carboxylic acid chlorides are also converted to their alcohols with high yields.     

Proprietes des α-phenylselenoaldehydes reactions de wittig conduisant a des α-hydroxyesters et cetones β,γ-ethyleniques et a des aldehydes α,β-ethyleniques

Wittig and Wittig-Horner reactions with α-phenylselenoaldehydes lead to allylic selenides. The corresponding selenoxides undergo 2,3-sigmatropic rearrangement providing a route to α-hydroxy β,γ-ethylenic esters and ketones in good yields. In a same way, we prepare, also enals with an additionnal carbon.     

Two-step allylic carbon insertion between ketone carbonyl and α carbons giving α-quaternary α-vinyl ketones

Ketones 1 were converted to α-quaternary α-vinyl ketones 2 by a two-step formal allylic carbon insertion between ketone carbonyl and α carbons, which involves the reaction of 1 with propargyltitanium reagents, derived from propargyl carbonates 3 and a divalent titanium reagent Ti(O-i-Pr)₄/2i-PrMgCl, and the following rearrangement of the resulting α-allenyl alcohols 4 with NBS.     

Gold(I)/Chiral N,N′-Dioxide–Nickel(II) Relay Catalysis for Asymmetric Tandem Intermolecular Hydroalkoxylation/Claisen Rearrangement

A highly efficient asymmetric cascade reaction between alkynyl esters and allylic alcohols has been realized. Key to success was the combination of a hydroalkoxylation reaction catalyzed by a π-acidic gold(I) complex with a Claisen rearrangement catalyzed by a chiral Lewis acidic N,N′-dioxide–nickel(II) complex. A range of acyclic α-allyl β-keto esters were synthesized in high yields (up to 99 %) with good diastereoselectivities (up to 97:3) and excellent enantioselectivities (up to 99 % ee) under mild reaction conditions. These products can be easily transformed into optically active β-hydroxy esters, β-hydroxy acids, or 1,3-diols.     

A new general approach for the stereocontrolled synthesis of functionalised γ- and δ-lactams

A new flexible approach for the stereoselective synthesis of substituted 1H-pyrrol-2(5H)-ones and 3,6-dihydro-1H-pyridin-2-ones has been developed. The general strategy employed the stereoselective reduction of a series of α,β-unsaturated ketones under chelation control to give the corresponding allylic alcohols. Overman rearrangement to install the key C-N bond followed by conversion to either prop-2-enoyl or but-3-enoyl derivatives and a ring closing metathesis reaction gave the target unsaturated γ- and δ-lactams. The synthetic utility of these compounds as building blocks was demonstrated by the preparation of the N-Boc derivative of (-)-coniine.     

3-甲基-5-苯砜基-3E-戊烯-1-醇的立体专一性合成

3-甲基-5-苯砜基-3E-戊烯-1-醇(1)是合成某些萜类化合物的重要中间体.它具有反式烯丙基苯砜基双键.Julia等曾报道用含砜基的环丙基醇的开环重排反应来实现这类化合物的立体选择性合成,但其开环前体不易得到.本文以4-羟基-2-丁酮(2)为起始原料,经4步反应立体专一性地合成了标题化合物1.合成路线短、操作简便、易于大量制备.合成路线用方程式表示如下:     

Asymmetric synthesis of allylic secondary alcohols: a new general approach for the preparation of α-amino acids

A new general approach for the synthesis of optically active α-amino acids has been developed. The key steps involve a ruthenium catalysed cross-coupling reaction to give a range of α,β-unsaturated ketones, which were then reduced to allylic secondary alcohols in the presence of a chiral CBS oxazaborolidine. A thermal Overman rearrangement was used to prepare a series of allylic trichloroacetimidates and these were converted under standard conditions to the target α-amino acids in good overall yields.     

Asymmetric addition of alkylzinc reagents to cyclic alpha,beta-unsaturated ketones and a tandem enantioselective addition/diastereoselective epoxidation with dioxygen

Although over 100 catalysts have been reported to catalyze the asymmetric addition of alkyl groups to aldehydes, these catalysts fail to promote additions to ketones with >90% enantioselectivity. This paper describes the asymmetric 1,2-addition of alkyl groups to conjugated cyclic enones to give allylic alcohols with chiral quaternary centers. The resultant allylic alcohols are converted into epoxy alcohols with excellent diastereoselectivities. Treatment of the epoxy alcohols with BF3.OEt2 induces a semipinacol rearrangement to provide alpha,alpha-dialkyl-beta-hydroxy ketones with all-carbon chiral quaternary centers. We also report a one-pot procedure for the asymmetric addition/diastereoselective epoxidation reaction. Simply exposing the reaction mixture to dioxygen after the asymmetric addition reaction is complete results in epoxidation of the allylic alcohol with high diastereoselectivity.     

3-Aza-cope rearrangement of quaternary N-allyl enammonium salts. Stereospecific 1,3 allyl migration from nitrogen to carbon on a tricyclic template

N-Allyl enamines can undergo a [3,3] sigmatropic rearrangement known as a 3-aza-Cope (or amino-Claisen) reaction. We explored a 3-aza-Cope reaction involving 1,3 allylic migration from nitrogen to carbon in N-allyl enammonium quaternary salts, exemplified by benzo[a]quinolizine 8 and pyrrolo[2,1-a]isoquinoline 13, with an interest in stereochemistry and mechanism. Salts 8 and 13 were accessed, respectively, through stereospecific allylation of hydroxy amines 4 and 11a/11b to give 7 and 12a/12b, which were dehydrated with trifluoroacetic acid. Allylic migration in these tricyclic tetrahydroisoquinolines occurred with high stereospecificity, with the major products 9 (from 8) and 15a (from 13) apparently deriving from a concerted suprafacial [3,3] rearrangement. The rearrangement of 8 to 9 was facile at 23 degrees C (t(1/2) = ca. 5 h) and was >98% stereospecific, whereas the rearrangement of 13 to 15a/15b required heating between 50 and 100 degrees C, with ca. 90-95% stereospecificity (t(1/2) = ca. 0.3 h at 100 degrees C). A deuterium-labeling experiment with 21 ((2)H-13) confirmed that allylic inversion accompanies the 1,3 migration en route to major isomer 22a ((2)H-15a), supporting the predominance of a concerted [3, 3] sigmatropic mechanism. However, the 5-10% loss of stereospecificity in the rearrangements of the pyrroloisoquinolines 13 and 21, reflected by formation of minor isomers 15b and 22b, respectively, indicates a minor nonconcerted reaction pathway.     

Base-Mediated Claisen Rearrangement of CF3-Containing Bisallyl Ethers

We have previously clarified that the strongly electron-withdrawing CF₃ group nicely affected the base-mediated proton shift of CF₃-containing propargylic or allylic alcohols to afford the corresponding α,β-unsaturated or saturated ketones, respectively, which was applied this time to the Claisen rearrangement after O-allylation of the allylic alcohols with a CF₃ group, followed by isomerization to the corresponding allyl vinyl ethers via the proton shift, enabling the desired rearrangement in a tandem fashion, or in a stepwise manner, the latter of which was proved to have attained an excellent diastereoselectivity with the aid of a palladium catalyst.     

Selenylated dienes: synthesis, stereochemical studies by Se NMR, and transformation into functionalized allenes

2-Phenylselanyl-1,3-dienes 3-8 were prepared by a Wittig or Wittig-Horner-Emmons procedure starting from α-phenylselanyl α,β-unsaturated aldehydes. Ratio and configuration of each diene isomers were determined by ⁷⁷Se and ¹H NMR. These dienes were then oxidized into selenoxides, which could be isolated in some cases. In THF, [2,3]-sigmatropic rearrangement of allylic selenoxides, selenimides, and dihalo-selenuranes occurred, yielding allenyl alcohols 12-15, allenyl carbamates 16c-19c, and 1-haloalkyl allenes 20c-22c, respectively.     

Synthesis of alkynyl ethers and low-temperature sigmatropic rearrangement of allyl and benzyl alkynyl ethers

Alpha-alkoxy ketones 3 can be transformed into 1-alkynyl ethers 5 by a two-step procedure involving formation of the enol triflate or phosphate and base-induced elimination. Performing the same reaction sequence with allylic alcohols (R2OH, R2 = allyl) furnishes instead gamma,delta-unsaturated carboxylic acid derivatives 6, derived from [3,3]-sigmatropic rearrangement of the intermediate allyl alkynyl ethers at -78 degrees C and trapping of the subsequently formed ketene with nucleophiles (Nu-H). Benzyl alkynyl ether 5 (R2 = benzyl) rearranges to indanone 7 upon heating to 60 degrees C.     

Allylic alcohols formation by oxidation of allylic phenyl tellurides. A possible [2,3] sigmatropic rearrangement of allylic telluroxides

Treatment of cinnamyl, 3-methyl-2-butenyl, and 2-cyclohexenyl phenyl tellurides with an oxidizing agent such as H₂O₂, NaIO₄ or t-BuOOH at room temperature under nitrogen affords 1-phenyl-2-propenol, 2-methyl-3-butene-2-ol, and 2-cyclohexenol as a sole or main product respectively in a high yield. The formation of these allylic alcohols can be best explained by assuming a [2,3]-sigmatropic rearrangement of the intermediate allylic telluroxides. These tellurides also react with oxygen, the formation of α.β-unsaturated carbonyl compounds being much increased in this oxidation.     

Rhodium complex-catalyzed cycloisomerization of allenenes: exo and endo cyclization depending on the auxiliary ligands

In the presence of a catalytic amount of a rhodium(I) complex, allenenes undergo cycloisomerization reactions resulting in the selective formation of exo-alkylidenecarbocycles and heterocycles. In the catalytic system of rhodium complexes with triaryl phosphites, cyclic 1,4- or 1,5-dienes are formed in good to excellent yields in the formal exo-cyclization mode via the metallacycle intermediate having an exo-alkylidene moiety. In this cycloisomerization, (E)- and (Z)-allenenes are transformed stereospecifically to the corresponding cyclic (E)- and (Z)-1,4-dienes, respectively. On the other hand, the reactions under carbon monoxide atmosphere exclusively afford seven-membered-ring products through an endo-mode cyclization. The unusual cyclization involves an allylic C-H activation process. The allenene bearing a silicon substituent at the olefinic terminus incorporates carbon monoxide to give the corresponding [2+2+1] cycloaddition product. This result apparently indicates that the catalysis of the rhodium complex is explained in terms of the oxidative cyclization of an allenene to furnish the key exo-alkylidene metallacycle intermediate at the first stage of the catalysis.     

Novel catalytic kinetic resolution of racemic epoxides to allylic alcohols

[formula: see text] The kinetic resolution of racemic epoxides via catalytic enantioselective rearrangement to allylic alcohols was investigated. Using the Li-salt of (1S,3R,4R)-3-(pyrrolidinyl)methyl-2-azabicyclo [2.2.1] heptane 1 as catalyst allowed both epoxides and allylic alcohols to be obtained in an enantioenriched form.