Claisen Rearrangement Chirality transfer

Because of the nature of the transition state in the pericyclic mechanism, optically active substrates with a chiral carbon at C-3 or C-4 transfer the chirality to the product, making this an enantioselective synthesis (see p. 1451 for an example in the mechanistically similar Claisen rearrangement). ... 

Wipf and coworkers used a Claisen rearrangement of allyl phenyl ethers 4-309 followed by an enantioselective carboalumination using the chiral Zr-complex 4-310 and trimethyl aluminum (Scheme 4.67) [104]. After an oxidative work-up of the intermediate trialkylalane, the corresponding alcohols 4-311 were obtained with up to 80% ee and 78% yield. One can also transfer an ethyl group using triethyl aluminum with even better ee-values (up to 92%), but the yields were rather low (42%) due to a more sluggish oxidative cleavage of the Al-C bond. 

The Diels-Alder reaction outlined above is a typical example of the utilization of axially chiral allenes, accessible through 1,6-addition or other methods, to generate selectively new stereogenic centers. This transfer of chirality is also possible via in-termolecular Diels-Alder reactions of vinylallenes [57], aldol reactions of allenyl eno-lates [19f] and Ireland-Claisen rearrangements of silyl allenylketene acetals [58]. Furthermore, it has been utilized recently in the diastereoselective oxidation of titanium allenyl enolates (formed by deprotonation of /3-allenecarboxylates of type 65 and transmetalation with titanocene dichloride) with dimethyl dioxirane (DMDO) [25, 59] and in subsequent acid- or gold-catalyzed cycloisomerization reactions of a-hydroxyallenes into 2,5-dihydrofurans (cf. Chapter 15) [25, 59, 60],... 

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

Chirality transfer also belongs to this class of methods. Thus, the configuration of (S)-(E)-Ar,jV-dimethyl-3-trimethylsilyl-4-hexenamide [(S)-(Zi)-2 on p 422] was solely assigned81 on the basis of the established stereochemistry of the Eschenmoser Claisen rearrangement (see P 475). 

Chiral allenes. A key step in a recent synthesis of the optically active pheromone of the male boll weevil (3) used the orthocstcr Claisen rearrangement for transfer of the chirality of the acetylenic alcohol 1 to the allene 2. The final product (3) shows a higher optical rotation than the naturally occurring material, which may... 

BINAP, 127, 171, 191, 194, 196 olefin reaction, 126, 167, 169, 191 organic halides, 191 Pancreatic lipase inhibitors, 357 Pantoyl lactone, 56, 59 para-hydrogen, 53 Peptides, matrix structure, 350 Perhydrotriphenylene, crystal lattice, 347 Pericyclic reactions, 212 chiral metal complexes, 212 Claisen rearrangement, 222 Diels-Alder, 212, 291 ene reaction, 222, 291 olefin dihydroxylation, 150 Phase-transfer reactions asymmetric catalysis, 333... 

In contrast, monofluoroallylic alcohol (S)-5 undergoes the Johnson-Claisen rearrangement in good yield after 7 hours at 130 C.33 The primary fluoride 6 is produced as the -isomer and with good 1,3-chiral transfer as the 7 -enantiomer. This ester is a key intermediate in the synthesis of 3 -fluoroapionuclcosides. 

More recently, Kitazume and co-workers found that allylic alcohols 7 undergo the Johnson Claisen rearrangement in higher yields when the reaction is run in a sealed tube at 130 C for 12 hours.35 Under these conditions. (/ )-7 is converted into 8 with high E stereoselectivity and complete 1,3-chiral transfer. 

Chiral 3-(trifluoromethyl)alk-4-enamides 4 can be prepared in the highly stereoselective Eschenmoser-Claisen rearrangement of chiral allylic alcohols 3 (Table 23).35 The. E-isomers of allylic alcohols 3 give 100% chirality transfer and slightly higher yields than the Z-isomers. 

The trifluoroacetimidate Claisen rearrangement has been successfully applied to several natural product syntheses in which excellent chiral transfer has been achieved, as illustrated in the conversion of 8 into 9.58 Although this methodology is designed to synthesize fluorine-free amines, it does illustrate the advantages that fluorine can often offer in tuning synthetic techniques. 

An aromatic Claisen rearrangement has been used as a key step in a total synthesis of racemic heliannuols C and E.18 A formal synthesis of (-)-perhydrohistrionicotoxin has used Claisen rearrangement of an amino acid ester enolate as the key step, in which almost total chirality transfer was observed from (S, )-oct-3-en-2-ol in the sense predicted by a chair-shaped transition state with chelation control of enolate geometry.19 Treatment of 1-(cyclohex-l-enyl)-6-methoxy-2-propargylindanol derivatives with base... 

Fig. 14.49. Trans-selective Iretand-Claisen rearrangements with 1,3-chirality transfer. (DMAP refers to 4-dimethyl-aminopyridine see Figure 6.9 on DHAP-catalyzed ester formation.)...

Fig. 14.50. Frans-selective Ireland-Claisen rearrangements with 1,4-chirality transfer. (See Figures 13.47 and 13.48, respectively, with R = vinyl in both cases, for preparations of the starting materials syn-A and anti-k, respectively.)...

Claisen rearrangement of allyl vinyl ethers. Thermal rearrangement of vinyl ethers (3) of sec-allylic alcohols in the presence of 1 or 2 leads to the aldehyde 4. Rearrangement of the optically active 5 is accompanied by transfer of chirality, particularly in the case of 1. 

Fig. 11.42. Preparation of an allyl enol ether, D, from allyl alcohol and a large excess of ethyl vinyl ether. Subsequent Claisen rearrangement D —> C proceeding with chirality transfer.

The Claisen rearrangement of (R)-l-methyl-(E)-2-butenyl hydroxy acetate (7) gives (2R,3S)-2-hydroxy-3-methyl-(E)-4-hexenoic acid (8) with complete 1,3-chirality transfer and with 98% syn-selectivity.4... 

The transposition of oxygen in allylic esters (R6 = alkyl, phenyl) or carbamates [R6 = N(CH3)2] has the same overall bonding changes as the thermal [3,3] sigmatropic Claisen or Cope rearrangements. Chirality transfer from C-l to C-3 is accompanied by 1,3 oxygen transposition (carbonyl O to allylic O ). 

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