Claisen rearrangement asymmetric induction

The use of the glucose chiral auxiliary by Lubineau et al. led to moderate asymmetric induction in the Claisen rearrangement (20% de) (Eq. 12.75).159 Since it could be removed easily, glucose functioned here as a chiral auxiliary. After separation of the diastereomers, enan-tiomerically pure substances could be obtained. 

Keywords Aza-Claisen rearrangement 3-Aza-Cope rearrangement Chirality transfer Asymmetric induction Charge acceleration... 

Discussing the stereochemical outcome of the Claisen rearrangements, two aspects had to be considered. On the one hand, the relative configuration of the new stereogenic centers was found to be exclusively syn in 201 and 202, pointing out the passing of a chair-like transition state c-a and c-jS, respectively, including a Z-acylammonium enolate structure (complete simple diastereo-selectivity/internal asymmetric induction). 

Asymmetric induction has been reported for a ketene Claisen rearrangement of the adducts of dichloroketene to chiral allyl thioethers as a route to precursors of optically active y-butyrolactones [504], An example of this sigmatropic step is given hereafter. 

The presence of jr-electron-donating substituents at the 2-position of the vinyl portion of the ether allows for significant acceleration of the Claisen rearrangement.314-318 Aliphatic Claisen rearrangements can proceed in the presence of organoaluminum compounds,286-319-320 although other Lewis acids have failed to show reactivity.286,321 324 Useful levels of (Z)-stereoselection and asymmetric induction have been obtained by use of bulky chiral organoaluminum Lewis acids.325 327... 

The cholesteric mesophase formed by cholesteryl p-nitrobenzoate at 200 °C has been used as the solvent to effect an asymmetric synthesis lrans-but-2-enyl p-tolyl ether gave the product of an ortho-Claisen rearrangement, 2-(but-1 -en-3 -yl)-4-methylphenol. This material exhibited circular dichroism, although neither the optical yield nor the configuration of the product is yet known.262 Decarboxylation of ethylphenylmalonic acid in cholesteryl benzoate at 160 °C (cholesteric liquid-crystalline phase) also proceeded with asymmetric induction to give (R)-(—)-2-phenylbutyric acid, with 18% optical yield.263 Electric dipole moments are reported for some esters of 5a-cholest-8(14)-en-3j8-ol there is some slight correlation with melting points.264... 

Asymmetric induction can be caused by the presence of a sulfinyl group within the system [63]. In 1997, the group of Metzner reported the first examples of a thio-Claisen rearrangement stereocontrolled by a sulfinyl group... 

Sulfone stabilized carbanions attached at C-2 substantially accelerate the Claisen rearrangement (Scheme 22) these species may be generated from either regioisomeric precursors [142]. These processes take place with high levels of internal asymmetric induction [ 143], and the scope of the process is broad and it has been extensively studied. This acceleration was also noted for the related sulfinyl carbanions, albeit with low yields and in the case of sulfilimines no internal asymmetric induction was observed [144]. 

Claisen Rearrangements. A modified BINOL-derived aluminum reagent is an effective chiral catalyst for asymmetric Claisen rearrangement of allylic vinyl ethers (eq 29). The use of vinyl ethers with sterically demanding C-3 substituents is necessary for the high level of asymmetric induction. 

A high degree of asymmetric induction has been realized in the carbanion-accelerated Claisen rearrangement of phosphorus-stabilized anions. Treatment of 1,3,2-oxazaphosphorinane (166) with freshly prepared lithium dimsylate led to a 95 5 ratio of a-methyl ketones (167) and (168) (Scheme 33). Li coordination combined with steric interactions provide the necessary control elements for stabilization of the highly organized allyl anion conformation (169). 

The arylsulfonyl carbanion accelerated Claisen rearrangement is completely regioselective and has also been found to be highly diastereoselective (Scheme 2). The stereochemical course of the reaction conforms to the familiar chair-like transition state model usually invoked for the classic thermal process. Recently, high degrees of asymmetric induction have been observed in tlie rearrangements of chiral cyclic phosphoramidate stabilized carbanion derivatives. ... 

The only examples of asymmetric Claisen rearrangements catalyzed by a chiral aluminum catalyst are those published by Yamamoto and coworkers [24-27]. The Claisen rearrangement of allyl vinyl ethers of type 91 (Sch. 13) can proceed via either of the two enantiomeric chair transition states 92 or 94. If a chiral Lewis acid is used to activate the process, the transition states become diastereomeric and preferential formation of one enantiomer of the product is possible. This is complicated because coordination of a chiral Lewis acid to the ether oxygen of allyl vinyl ether produces a new chiral center as indicated in 96 and asymmetric induction might occur from a substituent on aluminum to the oxygen and then from the oxygen to the C-3 carbon in the product. In their initial report, Maruoka, Banno, and Yamamoto found that a catalyst prepared from the 3,3 -disilyl-substituted BINOL 97 and trimethylaluminum was effective in this transformation [24]. The catalyst 98 was shown to be monomeric by measurement of freezing point depression. 

The final approach was elegantly presented by Panek [44]. Several optically active ( )-crotylsilanes are available via stereoselective Ireland-Claisen rearrangement of enantiomerically pure vinylsilanes. Addition of the chiral crotylsilanes to acetals or to mixtures of aldehyde and trimethylsilyl methyl ether is effected by la to afford homoallylic ethers in exceedingly high diastereo- and enantioselectivity (Sch. 13). Occasionally a stoichiometric amount of la is required for allylation of aliphatic acetals, preserving the excellent level of asymmetric induction. The synthesis of (-F)-macbecin I involving triple use of the strategy imderscores the utility of the la-catalyzed asymmetric allylation [44c]. 

A new perspective was opened up recently when Denmark demonstrated diat with chirally modified phosphoryl-activated allenes an asymmetric induction could be effected. From easily generated allenyl phosphoramidates containing an optically active amino alcohol, the diastereomeric adducts (37) and (39) could be obtained by addition of dlyl alcohol. When the separated adducts were employed in the carb-anionic Claisen rearrangement, a remarkable asymmetric induction (90 10) could be achieved with preferential formation of the diastereomers (38) or (40) respectively, whereas in a thermal reaction no stereoselection was observed (Scheme 63). Another example of an asymmetric induction in Claisen rearrangements is reported by Welch. ... 

New prospects are opened up with glycolate ester derivatives having an incorporated stereogenic center outside the Claisen system which may cause asymmetric induction during the rearrangement, as can be seen in a recent example (Scheme 69). ... 

Beside the simple allylic N C transformation, which allows an allylation in the a-position of aldehydes avoiding completely the problem of 0- versus C-alkylation (Scheme 74), the amino-Claisen rearrangement seems especially suited for effecting asymmetric induction by employing optically active amine systems. ... 

With a chiral auxiliary in (42) such as 1-phenylethylamine (R = CHMePh), the diastereomeric excess in the reaction is low (de < 30%) and only improves somewhat when TiCU catalysis is used to lower the temperature and simultaneous 1,4- and l,S-asymmetric induction is attempted. A more promising approach was found in the amino-Claisen rearrangement of IV-allylketene lV,(7-acetals (44), which are... 

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