Orthoester allylic

The mechanism and stereochemistry of the orthoester Claisen rearrangement is analogous to the Cope rearrangement. The reaction is stereospecific with respect to the double bond present in the initial allylic alcohol. In acyclic molecules, the stereochemistry of the product can usually be predicted on the basis of a chairlike TS.233 When steric effects or ring geometry preclude a chairlike structure, the reaction can proceed through a boatlike TS.234... 

Scheme 6.15 gives some representative examples of the orthoester Claisen rearrangement. Entry 1 is an example of the standard conditions for the orthoester Claisen rearrangement using triethyl orthoacetate as the reactant. The allylic alcohol is heated in an excess of the orthoester (5.75 equivalents) with 5 mol % of propanoic acid. Ethanol is distilled from the reaction mixture. The E-double bond arises from the chair TS. 

A. Claisen Rerrangements of Ketene Aminats and Imidates. A reaction that is related to the orthoester Claisen rearrangement utilizes an amide acetal, such as dimethylacetamide dimethyl acetal, in the exchange reaction with allylic alcohols.257 The products are y, 8-unsaturated amides. The stereochemistry of the reaction is analogous to the other variants of the Claisen rearrangement.258... 

Thermolysis of the oxadiazoline (123) gives rise to the corresponding dialkoxy-carbene, which can be trapped by reaction with f-butanol to form orthoesters. The formation of a regioisomeric mixture of esters was explained by fragmentation of the carbene to radicals (124) which recombine at either end of the allyl system. 

Heating of an allylic alcohol with an excess of trialkyl orthoacetate in the presence of trace amounts of a weak acid to give a mixed orthoester. The orthoester loses ethanol to generate the ketene acetal, which undergoes [3,3]-sigmatropic rearrangement to give a Y,5-unsaturated ester. 

Claisen orthoester rearrangement.2 This reagent can be used to prepare methyl a-substituted acrylates from allylic alcohols. 2,4,6-Trimethylbcnzoic acid is used as the acid catalyst.1... 

Elimination of two equivalents of ROH after condensation between an allyl alcohol and an orthoester will provide the allyl vinyl ether which undergoes the [3,3]-sigmatropic rearrangement. 

Treatment of compound 95 with DDQ produces the hydrolysis of the orthoester when wet acetone is used as solvent and the oxidation of the allylic alcohol when dry benzene is employed. Apparently, the mechanism of the orthoester hydrolysis involves a charge-transfer intermediate, with no influence from the acidity of the generated DDQ hydroquinone. 

Nicolaou KC, Mitchell HJ, Flyaktakidou KC, Suzuki H, Rodriguez RM, 1,2-Seleno migrations in carbohydrate chemistry Solution and solid-phase synthesis of 2-deoxy glycosides, orthoesters, and allyl orthoesters, Angew. Chem. Int. Ed., 39 1089-1093, 2000. 

S-Orthoesters seldom appear in organic synthesis but they do occupy one useful niche. In 1967 Seebach245-246 introduced tris(methylthio)methyhithium as an acyl anion equivalent of a carboxyl group. It was sufficiently stable and nucleophilic to react with a range of electrophiles. For example, nucleophilic substitution of the allylic chloride 121,1, followed by mercury(Il)-mediated hydrolysis of the SS-orthoester intermediate 121,2, gives the p,y-unsaturated car-... 

CLy -Enals and -enones.17 The TiCl4-catalyzed reaction of lithium trialkyl(l-al-kynyl)borates with methyl vinyl ketone (10, 402) has been extended to a similar reaction with orthoesters, which results in allylic boranes that are oxidized to a,p-enones and -ei als (equation I). 

Nicolaou [46] has also exploited a seleniiun Unker cleaved using radical conditions in the solid-phase synthesis of 2-deoxyglycosides, 2-deoxy-orthoesters and 2,3-allyl orthoesters. Resin-bound tributyltin selenolate 251 was conveniently synthesized in two steps from a selenenyl bromide resin. Treatment of 251 with a trichloroacetimidate donor gave resin-bound se-... 

A mercury-free route to allyl vinyl ethers that relies on the Michael addition of allyl alcohols to unsubstituted alkenyl sulfoxides, followed by thermal loss of sulfenic acid and concurrent Claisen rearrangement has been described [145]. This methodology has been applied to the synthesis of isocar-bacyclin [146]. Posner reported an acid-catalyzed protocol that produces conjugated dienoate esters from allylic alcohols and a sulfinyl orthoester [147]. Additionally, the use of propargyl alcoholates and a chloro alkenyl sulfox-... 

Extremely useful ramifications of the Claisen rearrangement emerged with Johnson s discovery of the orthoester variant of this transformation. His approach (Scheme 2.156) involved the following sequence of steps, which were carried out in one reaction vessel (i) transesterification of the orthoester with an allylic alcohol to give 490 (ii) elimination to form the intermediate ketene acetal 491 and (iii) [3,3] sigmatropic rearrangement to yield the y, -unsaturated ester 492. The Johnson-Claisen procedure is properly considered to be one of the most efficient methods available to prepare y,(5-unsaturated esters such as 492. ° ... 

Scheme 51 presents an entirely different mode of catalyzed [4 + 2] cycloadditions. Thus irimediylsilyl triflate or triflic acid apparently transform vinyl orthoesters and acrolein acetals to powerful transient allyl cation dienophiles (214) and (219), respectively. The ionic Diels-Alder reactions (213) (216)... 

The success of the Claisen-Cope rearrangement need not be limited to the production of aldehydes via enol ethers. Allylic alcohol (58) is successively transposed into a mixture of allylic isomers (59 Scheme 4), and is subjected to an orthoester Claisen rearrangement at 150 "C to provide ester (61). The moderate temperature of the Claisen step permits the isolation of an intermediate (c/. Scheme 3) prior to the final Cope rearrangement (195 C) to. y-unsaturated esters (60). The esters (60) are a 55 45 mixture of ( )- and (Z)-double bond isomers owing to the near equal steric bulk of the methyl and acetic acid residues in the transition state for the Cope rearrangement. ... 

---