Chirality intramolecular transfer

Goering et al. reported asymmetric aromatic Claisen rearrangement by intramolecular chirality transfer related to the study on elucidation of reaction mechanism [62]. The thermal rearrangement of the E isomer of (J )-but-3-en-2-yl phenyl ether 69 proceeded at 200 °C to give a mixture of E isomer 70 and Z isomer 71 in a ratio of 82 18, although the optical purity of each product was not shown. 

A similar example of intramolecular chiraUty transfer rearrangement employing thermal conditions and a Lewis acid (BClj) as the catalysis conditions was also reported [3 la]. 

One of the successful examples of an intramolecular chirality transfer reaction was reported by Takano et al. [63], which is a key step for the total synthesis of (+)-latifine, isolated as the first example of tetrahydroisoquinoline alkaloid possessing a 4-phenyl-5,6-dioxygenated substitution pattern. The rearrangement of the chiral substrate 75 prepared from D-mannitol proceeded under the thermal conditions (N,N-dimethylaniline, reflux) to give the product 76 in 76% yield. Formation of the T-configuration was explained by the chair-like transition state 77. 

Recently, some elegant work was reported on the preparation of chiral ortho-substituted phenol derivatives through intramolecular chirahty transfer by Trost et al. [64]. Chiral substrate 78 was prepared in excellent enantiomeric excess from phenol and racemic aUyUc carbonate through asymmetric O-aUylation with dynamic kinetic asymmetric transformation. They showed that a europium(lll) tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionate) Eu(fod)3-catalyzed rearrangement proceeds at 50 °C to give product 79 with complete chirahty transfer. 

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As will be described below, self-reproduction of chirality can be accomplished through alkylations of endocyclic as well as exocyclic enolates. It generally entails (i) production of a ring containing a temporary, auxiliary chiral center by derivatization of an optically active a-hydroxy or a-amino ester (ii) formation of an enolate by deprotonation at the original asymmetric a-carbon atom (iii) use of intramolecular chirality transfer to control the stereochemistry of alkylation of the enolate and (iv) generation of the chiral a-alkylated ester by hydrolysis. 

Enamines derived from ketones are allylated[79]. The intramolecular asymmetric allylation (chirality transfer) of cyclohexanone via its 5-proline ally ester enamine 120 proceeds to give o-allylcyclohexanone (121) with 98% ee[80,8l]. Low ee was observed in intermolecular allylation. Similarly, the asymmetric allylation of imines and hydrazones of aldehydes and ketones has been carried out[82]. 

Complete chirality transfer has been observed in the intramolecular allyla-tion of an alcohol with the activated allylic ester of 2,6-dichlorobenzoic acid 338 to give the 2-substituted tetrahydrofuran 339[208]. 

This facilitates intramolecular hydride transfer resulting in a Ru-hydroxy ester complex (66) which readily releases the chiral product. When an (R)-BINAP-Ru catalyst is used, the R enantiomer is obtained in >99% ee. The chirality of the BINAP ligand accounts for the difference in energy between the possible transition states TS and TS. ... 

Chan has discovered a completely atropdiasteroselective synthesis of a biaryl diphosphine by asymmetric intramolecular Ullmann coupling or Fe(m)-promoted oxidative coupling. A chiral atropisomeric biaryl bisphosphine ligand 2 was synthesized through this central-to-axial chirality transfer.38 Recently, a xylyl-biaryl bisphosphine ligand, Xyl-TetraPHEMP, was introduced by Moran, and is found to be effective for the Ru-catalyzed hydrogenation of aryl ketone.39... 

New chiral oxazaborolidines that have been prepared from both enantiomers of optically active inexpensive a-pinene have also given quite good results in the asymmetric borane reduction of prochiral ketones.92 Borane and aromatic ketone coordinate to this structurally rigid oxazaborolidine (+)- or (—)-94, forming a six-membered cyclic chair-like transition state (Scheme 6-41). Following the mechanism shown in Scheme 6-37, intramolecular hydride transfer occurs to yield the product with high enantioselectivity. With aliphatic ketones, poor ee is normally obtained (see Table 6-9). 

The intramolecular cyclization of l,2-dien-7-ynes and l,2-dien-6-ynes regiospecifically affords the corresponding titanacycles, which react with protons, carbon monoxide, aldehydes, or imines to give single products, as shown in Eqs. 9.56 and 9.57 [102], As the formation of titanacycles and their subsequent reaction with externally added reagents such as carbon monoxide (Eq. 9.56) or an aldehyde (or imine) (Eq. 9.57) proceeds with excellent chirality transfer, this represents a new method for synthesizing optically active cyclopentane derivatives from optically active allenes [102]. 

Under more basic conditions, a-elimination predominates and insertion of the carbene 40 to the solvent gives racemic 22. Non-basic and poorly nucleophilic conditions allow neighboring group participation to form the rearranged substitution product 23 with complete chirality transfer. The participation can be considered as an intramolecular nucleophilic substitution, and does occur only when it is preferable to the external reactions. Under slightly basic conditions with bases in HFIP, participation is allowed, and the weak base can react with the more electrophilic vinylic cation 21 (but not with the iodonium ion 19). A suitably controlled basicity can result in the formation of cycloalkyne 39, which is symmetrical and leads to racemization. These reactivities are illustrated in Scheme 6. 

In the aldol-Tishchenko reaction, a lithium enolate reacts with 2 mol of aldehyde, ultimately giving, via an intramolecular hydride transfer, a hydroxy ester (51) with up to three chiral centres (R, derived from rYhIO). The kinetics of the reaction of the lithium enolate of p-(phenylsulfonyl)isobutyrophenone with benzaldehyde have been measured in THF. ° A kinetic isotope effect of fee/ o = 2.0 was found, using benzaldehyde-fil. The results and proposed mechanism, with hydride transfer rate limiting, are supported by ab initio MO calculations. 

It has recently been shown that when the tetrahedral intermediate of the reaction is cyclic, it is a better donor of nucleophilic CF3. These cyclic intermediates can be generated intramolecularly from trifluoroacetamides or trifluorosulfmamides derived from (9-silylated ephedrine. These reagents are able to trifluoromethylate aldehydes and ketones, even in the case of enolizable substrates, as a strong base is not required (Figure 2.34). However, while the source of CF3 is chiral, there is no chirality transfer to the addition product, and the replacement of ephedrine by other chiral amino alcohols did not show any improvement. " Similar to asymmetric trifluoromethylation with the Ruppert reagent, only the use of a fluoride salt of cinchonine can increase the enantioselectivity. " " ... 

Intramolecular pinacol coupling of 2,2 -biaryldicarbaldehyde with samarium(ll) iodide shows that axial chirality transfer to central chirality proceeds in a stereospecific manner. ... 

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