Propargylic allylic alcohols

Sc(OTf)3, AcOH, p-nitrobenzoic anhydride or Sc(OTf)3, AC2O, 66- >95% yield. The lower yields are obtained with allylic alcohols propargylic alcohols give higher yields. Phenols are effectively acylated with this catalyst, but at a much slower rate than simple aliphatic alco-hols. The method was shown to be superior to most other methods for macrolactonization with minimum diolide formation. 

Resolution by transesterification. Using vinylic acetates to esterify allyl alcohols, propargyl alcohols, 2-phenylthiocycloalkanols, a-hydroxy esters," methyl 5-hydroxy-2-hexenoates, and 2-substituted 1,3-propanediols, the enantioselective esterification provides a means of separation of optical isomers. Vinyl carbonates are also resolved by lipase-mediated enantioselective conversion to benzyl carbonates. Other esters that have also been used in the kinetic resolution include 2,2,2-tri-fluoroethyl propionate. There is a report on a double enantioselective transesterification" of racemic trifluoroethyl esters and cyclic meso-diols by lipase catalysis. 

In a formally similar reaction, the 4-methanesulfonyl-/3-lactam (95) undergoes displacement of methanesulfinate on treatment with propargylic or allylic alcohols in the presence of a Lewis acid catalyst to give a mixture of the cis- and tr<2Ms-4-alkoxy-/3-lactams (96) and (97) (79JCS(P1)2268). 

Propargylic alcohols are reduced by reaction with lithium aluminum hydride and subsequent hydrolysis to ( J-allylic alcohols via an organoaluminum intermediate (A) as shown below ... 

CH2(OMe)2, CH2CI2, TfOH, 4 h, 25°, 65% yield. This method is suitable for the formation of primary, secondary, allylic, and propargylic MOM ethers. Tertiary alcohols fail to give a complete reaction. 1,3-Diols give methylene acetals (89% yield). 

In the case of allylic or propargylic diols, the nonallylic (propargylic) alcohol is protected. 

Previous syntheses of terminal alkynes from aldehydes employed Wittig methodology with phosphonium ylides and phosphonates. 6 7 The DuPont procedure circumvents the use of phosphorus compounds by using lithiated dichloromethane as the source of the terminal carbon. The intermediate lithioalkyne 4 can be quenched with water to provide the terminal alkyne or with various electrophiles, as in the present case, to yield propargylic alcohols, alkynylsilanes, or internal alkynes. Enantioenriched terminal alkynylcarbinols can also be prepared from allylic alcohols by Sharpless epoxidation and subsequent basic elimination of the derived chloro- or bromomethyl epoxide (eq 5). A related method entails Sharpless asymmetric dihydroxylation of an allylic chloride and base treatment of the acetonide derivative.8 In these approaches the product and starting material contain the same number of carbons. 

The stereochemistry of the first step was ascertained by an X-ray analysis [8] of an isolated oxazaphospholidine 3 (R = Ph). The overall sequence from oxi-rane to aziridine takes place with an excellent retention of chiral integrity. As the stereochemistry of the oxirane esters is determined by the chiral inductor during the Sharpless epoxidation, both enantiomers of aziridine esters can be readily obtained by choosing the desired antipodal tartrate inductor during the epoxidation reaction. It is relevant to note that the required starting allylic alcohols are conveniently prepared by chain elongation of propargyl alcohol as a C3 synthon followed by an appropriate reduction of the triple bond, e. g., with lithium aluminum hydride [6b]. 

With 1-2 mol% of 64b, racemic mixtures of aryl-alkyl carbinols 86 [103], propargylic [104] and allylic alcohol [105] 88 and 87, respectively, were resolved (Fig. 43). The best selectivities were attained for aryl-alkyl-carbinols 86, where the unreacted isomer was obtained with excellent ees after 55% conversion, while propargyl alcohols 88 required clearly higher conversions for high ees in the remaining starting material [106]. 

Benzylic, allylic and propargylic positions enhance the cathodic cleavage rate of C— heteroatom bonds as, for example, in the reduction of benzylic and allylic halides or alcohols . Similar activated sulphones, due to their acidity, are in a class apart. Figure 8 shows the similitude between the cathodic behaviour of an allylic sulphone and its isomer, i.e., the corresponding vinylic sulphone when the electrolyses are run in an aprotic solvent. However, in the presence of an excess of proton donor, discrepancies appear. 

A chemoenzymatic methodology has been developed using indium-mediated allylation (and propargylation) of heterocyclic aldehydes under aqueous conditions followed by Pseudomonas cepacia lipase-catalyzed enantioselective acylation of racemic homoallylic and homo-propargylic alcohols in organic media.192... 

In-mediated propargylation of acetals and ketals with various allyl or propargyl bromides in aqueous media successfully provided the corresponding homoallylic or homopropargyhc (and allenyhc) alcohols (Eq. 8.81)207... 

Under the catalytic action of Rh2(OAc)4, formation of a propargylic ether from a terminal alkyne (229, R1=H) is preferred as long as no steric hindrance by the adjacent group is felt162,218>. Otherwise, cyclopropenation may become the dominant reaction path [e.g. 229 (R1 = H, R2 = R3 = Me) and methyl diazoacetate 56% of cyclopropene, 36% of propargylic ether162)], in contrast to the situation with allylic alcohols, where O/H insertion is rather insensitive to steric influences. 

A ruthenium(n)-indenyl complex, which is an efficient catalyst for the isomerization of allylic alcohols, is also an effective catalyst for the isomerization of propargylic alcohols to both a,/3-enals and a,/ -enones (Scheme 57).96 In this reaction, the addition of 20—40 mol% InClj is highly effective. The reaction exhibits extraordinary chemoselectivity and a variety of functional groups are unaffected, which allows a highly efficient synthesis of dienals (R1 =Me2C = CH, R2 = H). 

An important variant for transition metal-catalyzed carbon-nitrogen bond formation is allylic substitution (for reviews, see1,la lh). Nucleophilic attack by an amine on an 7r-allyl intermediate, generated from either an allylic alcohol derivative,2 16,16a 16f an alkenyloxirane,17-19,19a-19d an alkenylaziridine19,19a 19d, or a propargyl alcohol derivative,21,21a 21d gives an allylic amine derivative. 

The optically active propargylic and allylic alcohols thus obtained are important synthetic intermediates in the enantioselective synthesis of insect pheromones, prostaglandins, prostacyclins, and many other bioactive compounds (Scheme 6-26).53... 

Selective oxidation of allylic alcohols.1 This zircononcene complex when used in catalytic amount can effect an Oppenauer-type oxidation of alcohols, including allylic ones, in the presence of a hydrogen acceptor, usually benzaldehyde or cyclohexanone. This system oxidizes primary alcohols selectively in the presence of secondary ones. Thus primary allylic alcohols are oxidized to the enals with retention of the configuration of the double bond in 75-95% yield. The method is not useful for oxidation of propargylic alcohols. 

Double bonds in conjugation to a carbonyl group and allylic and propargylic alcohols. But the isolated double and triple bonds are inert. 

Still, occasionally the other fuctional groups react as well, for example in 38 under basic conditions the propargylic alcohol isomerizes to the a,/3-unsaturated ketone [73] (Scheme 1.15), whereas in a closely related substrate from the synthesis of a subunit of compactin an allylic alcohol remains unchanged [74],... 

The isomerisation of allyl and propargylic alcohols involves the 1,3-shift of an oxygen atom rather than a hydrogen atom. Isomerisation of allyl alcohols can be catalysed by a variety of metal oxo complexes and in this instance the reaction does not involve metal carbon bonds as we will see. One could imagine that allylic metal species can participate in isomerisation of allylic compounds, but for the alcohols themselves this is not an easy reaction. In chapter 13 reactions of allyl acetates and the like, which are more prone to... 

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