Claisen rearrangement asymmetric

As mentioned for the Ireland-Claisen rearrangement, asymmetric Claisen rearrangement reactions are well known.Chiral Lewis acids have been designed for... 

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

Asymmetric Claisen rearrangement reactions are well known. Chiral Lewis... 

Even if organocatalysis is a common activation process in biological transformations, this concept has only recently been developed for chemical applications. During the last decade, achiral ureas and thioureas have been used in allylation reactions [146], the Bayhs-Hillman reaction [147] and the Claisen rearrangement [148]. Chiral organocatalysis can be achieved with optically active ureas and thioureas for asymmetric C - C bond-forming reactions such as the Strecker reaction (Sect. 5.1), Mannich reactions (Sect. 5.2), phosphorylation reactions (Sect. 5.3), Michael reactions (Sect. 5.4) and Diels-Alder cyclisations (Sect. 5.6). Finally, deprotonated chiral thioureas were used as chiral bases (Sect. 5.7). 

In 1997 the first asymmetric aza-Claisen rearrangement was reported by Overman et al. [55], which made use of diamines as bidentate ligands for Pd(II), allowing for moderate enantioselectivities. In the same year, Hollis and Overman described the application of the planar chiral ferrocenyl palladacycle 38 as a catalyst for the enantioselective aza-Claisen rearrangement of benzimidates 39 (Fig. 19) [56]. A related ferrocenyl imine palladacycle provided slightly inferior results, while a benzylamine palladacycle lacking the element of planar chirality was not able to provide any enantioselectivity [57]. 

Fig. 19 Asymmetric Azti-Claisen Rearrangement of benzimidates 39 using amino palladacycle 38...

Fig. 20 Asymmetric azti-Claisen rearrangement of benzimidates using oxazoline palladacycle precatalyst 41...

Fig. 21 Asymmetric crza-Claisen rearrangement of benzimidates using bispalladacycle precatalyst 42...

Fig. 22 Asymmetric tiza-Claisen rearrangement of benzimidate 39a using the trispalladium species 43...

Fig. 23 Asymmetric tizti-Claisen rearrangement of trifluoroacetimidates using precatalyst 41...

Fig. 25 Asymmetric aza-Claisen rearrangement of trifluoroacetrmidates 44 using precatalyst 47a...

Fig. 26 Asymmetric aza-Claisen rearrangement of trifluoroacetimidates 49 generating iV-substi-tuted quaternary stereocenters...

Fig. 30 Asymmetric aza-Claisen rearrangement of (Z)-configured trifluoroacetimidates 44 3.1.2 Bispalladium-Catalyzed Michael-Addition of a-Cyanoacetates...

Kang J, Yew KH, Kim TH, Choi DH (2002) Preparation of bis [palladacycles] and application to asymmetric aza-Claisen rearrangement of allylic imidates. Tetrahedron Lett 43 9509-9512... 

Fischer DF, Xin ZQ, Peters R (2007) Asymmetric formation of allylic amines with N-substimted quaternary stereocenters by Pd -catalyzed Aza-Claisen rearrangements. Angew Chem Int Ed 46 7704-7707... 

Xin ZQ, Fischer DF, Peters R (2008) Catalytic asymmetric formation of secondary allylic amines by Aza-Claisen rearrangement of trifluoroacetimidates. Synlett 1495-1499... 

Fischer DF, Barakat A, Xin ZQ, Weiss ME, Peters R (2009) The asymmetric Aza-Claisen rearrangement development of widely applicable pentaphenylferrocenyl palladacycle catalysts. Chem Eur J 15 8722-8741... 

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. 

Hemiacetal 25 [(3 ,4S,l E)-3,4-bis(r-butenyl)tetrahydro-2-furanol] is the male pheromone of the spined citrus bug (Biprorulus bibax). Scheme 38 summarizes Mori s synthesis of 25 [61]. Claisen rearrangement (A B) and lipase-catalyzed asymmetric acetylation [meso-C >(5S,6R)-D] were the two key steps of the synthesis. Further purification of D was executed at the stage of its crystalline derivative E. In this particular case, the unnatural (3S,4R,l E)-25 was as active as the natural (3R,4S,VE)-25. Accordingly, a more efficient synthesis of ( )-25 was achieved by the rearrangement of F, avoiding the use of toxic HMPA [62]. 

Diastereoselective asymmetric thio-Claisen rearrangement has been carried out by the reaction of thioamides with allyllic bromide (Scheme 37).76... 

Scheme 4.22 Asymmetric synthesis of allene 89 by the orthoester Claisen rearrangement.

Scheme 4.23 Chiral allene synthesis via asymmetric aldol reaction and Claisen rearrangement.

Scheme 4.24 Asymmetric synthesis of enprostil 95 via Claisen rearrangement.

Scheme 4.25 Asymmetric synthesis of clavepictines 99 and 100 via Claisen rearrangement.

This section will focus on recent examples of asymmetric [3,3]-sigmatropic rearrangements involving dienes and polyenes. Attention will be given to Cope and Claisen rearrangements, as well as to several of their variants. For more exhaustive reviews of the subject, the reader is referred elsewhere69,70. 

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). 

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