Claisen rearrangements stereocontrol

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... 

There are a number of powerful synthetic reactions which join two trigonal carbons to form a CC single bond in a stereocontrolled way under proper reaction conditions. Included in this group are the aldol, Michael, Claisen rearrangement, ene and metalloallyl-carbonyl addition reactions. The corresponding transforms are powerfully stereosimplifying, especially when rendered enantioselective as well as diastereoselective by the use of chiral controller groups. Some examples are listed in Chart 20. 

A salient structural feature of intermediate 18 (Scheme 2b), the retrosynthetic precursor of aldehyde 13, is its y,r5-unsaturated ester moiety. As it turns out, the Johnson ortho ester variant of the Clai-sen rearrangement is an excellent method for the synthesis of y,<5-unsaturated esters.11 In fact, the Claisen rearrangement, its many variants included, is particularly valuable in organic synthesis as a method for the stereocontrolled construction of trans di- and tri-substituted carbon-carbon double bonds.12,13 Thus, it is conceivable that intermediate 18 could be fashioned in one step from allylic alcohol 20 through a Johnson ortho ester Claisen rearrangement. In... 

The aza-[2,3]-Wittig rearrangement [47] and the related aza-[3,3]-Claisen rearrangement [48] of vinylaziridines are elegant examples of expansion of the aziridine ring in a stereocontrolled fashion (Scheme 38). 

A well-developed concept to achieve high stereocontrol in the formation of a quaternary chiral center has been introduced by Fraser-Reid, using the Claisen rearrangement along two lines. In the first approach a type III branched-chain sugar is prepared by Wittig... 

Some applications of the thio-Claisen rearrangement to the syntheses of thiocarbonyl compounds, particularly unsaturated dithiocstcrs and thionesters, and of its stereocontrol aspects are reviewed in [120]. A particularly high stereoselectivity was observed with S-allyl derivatives of P-hydroxydithioesters syn products were obtained exclusively, according to the accompanying scheme [495,496]. 

An interesting aspect of the allylic C-H insertion is that the products are y,6-unsaturated esters. Traditionally, y,6-unsaturated esters are most commonly prepared by a Claisen rearrangement, especially if stereocontrol is required. Diastereocontrol is also possible in the C-H insertion as long as the reaction occurs at a methylene site where there is good size differentiation between the two substituents [21]. An example is the reaction between 17 and the silylcyclohex-ene 18 which forms the C-H insertion product 19 in 88% de and 97% ee [21]. Other catalysts such as Rh2(.R-BNP)4 and Rh2(S-MEPY)4 have been explored for allylic C-H activation of cyclohexene but none were was as effective as Rh2(S-DOSP)4 [22]. 

Finally, using a variant of the Claisen rearrangement (Malherbe-Bellus712), nine-membered lactones may be synthesized in reasonable yields with some stereocontrol. 

With stereocontrol mastered, the preparation of 32 was optimized. The efficiency of the Claisen rearrangement strongly depended upon the conditions employed. For example, the amount of base needed to be strictly controlled in that at least two equivalents of base were required. With a single equivalent of base, only self-condensation was observed and further, excess base did not improve the yield. Perhaps the by-products formed early during enolization react further with remaining... 

In a series of elegant studies, Paquette and coworkers demonstrated the potential of the Claisen rearrangement for the stereocontrolled total synthesis of natural products. Dehydrative coupling of (2)-3-(trimethylsilyl)-2-propen-l-ol with cyclohexanone (51) under Kuwajima s conditions, followed by rearrangement of enol ether (52) in decalin, led in excellent stereoselectivity (>99 1) to aldehyde (53 Scheme 8). Concise construction of the eight-membered core of acetoxycrenulidine was achieved by intramolecular phenylseleno etherification of lactone (54), introduction of the exocyclic vinyl ether double bond by selenoxide elimination and subsequent Claisen rearrangement (Scheme 9, 66% from 54). ... 

The Ireland modification utilizes silyl ketene acetals derived from allyl ester eno-lates and provides a general method to effect stereocontrolled Claisen rearrangements under mild conditions, making it possible to apply the reaction to acid-sensitive and thermally labile substrates. Moreover, by proper choice of the reaction conditions, one can control the geometry of the enol ethers and hence the stereochemistry of the new C-C bond that is produced in the rearrangement step." ... 

To exploit the whole capacity of the Claisen rearrangement, appropriate methods for the preparation of the allyl vinyl ethers starting from allyl alcohols are necessary. The classical approach involves vinyl-ation with simple vinyl ethers or acetals. Unfortunately these methods fail with more complex systems and do not allow, except in the case of cyclic enol ethers, control of the stereochemistry of the substituted enol ether double bond. Until recently it was only possible to generate such substituted systems with appreciable stereocontrol via ketene N.O-acetals. Their preparation by addition of lyl alcohols to substituted ynamines can lead to adducts of either ( )- or (Z)-geometry, depending upon the conditions used (Scheme 60). 

The potential of the ester enolate Claisen rearrangement for the stereocontrolled synthesis of highly functionalized, complex systems has been demonstrated in numerous applications in natural product synthesis. Utilizing the 1,3-chirality transfer Ireland has synthesized oxygen heterocycles with chiral side chains, such as are found as units in polyether antibiotics and macrolides, starting from enantiomerically pure furanoid or pyranoid glycal systems of type (41), which are easily accessible from carbohydrates (Scheme 65). ... 

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