Claisen chiral auxiliary

The possibility of using chiral auxiliaries or chiral catalysts to achieve enantio-selective Claisen rearrangements has been explored.253 One approach is to use chiral boron enolates. For example, enolates prepared with the chiral diazaborolidine bromide O lead to rearranged products of more than 95% enantiomeric excess.254... 

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. 

Asymmetric Pericyclic Reactions. Several reports illustrate the utility of fra/is-2,5-dimethylpyirolidine as a chiral auxiliary in asymmetric Claisen-type rearrangements, [4 + 2], and [2 + 2] cycloaddition reactions. The enantioselective Claisen-type rearrangement of N,0-ketene acetals derived from tram-2,5-dimethylpyrrolidine has been studied. For example, the rearrangement of the iV.O-ketene acetal, formed in situ by the reaction of A-propionyl-fra/w-(25,55)-dimethylpyrrolidine with ( )-crotyl alcohol, affords the [3,3]-rearrangement product in 50% yield and 10 1 diastereoselectivity (eq 9). 

Generally, Claisen rearrangement of ring-bearing substrates with remote asymmetric centers has led to higher stereoselectivities than in the acyclic series. Kurth and cowoikers used amino acid derived chiral auxiliaries such as (302) for the preparation of enantiomerically pure carboxylic acids. The excellent facial selectivity in these systems was hampered, however, by poor chair vs. boat selectivities. 

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... 

The accelerating influence of water as a solvent on the rate of Claisen rearrangement has also been demonstrated. The use of glucose as chiral auxiliary by Auge et led to moderate asymmetric induction in the Claisen rearrangement. After removal of the glucose moiety followed by separation of diastereomers, an enantiomerically pure product was obtained (Scheme 5.14). 

Optically active phosphonamidates have been used for chiral auxiliary based Claisen rearrangements (see Section 1.6.3.1.1.5.2.2. p 3508)105 I06. 

A highly selective asymmetric C-C bond formation is achieved in the synthesis of dihydroox-azoles 5 and 6 via the aza-Claisen rearrangement of /V-allylketene A,0-acctals 3. Diastereose-lectivities in the range 84 96% are obtained. Hydrolysis of the products 5 and 6 allows the chiral auxiliary to be recycled640 641. 

The chiral auxiliary mediated aza-Claisen rearrangement of /V-allylketcnc. V.O-acetals also allows the diastereoselective construction of quaternary carbon centers642. Butyllithium proved to be an unsuitable base for the neutralization step in this case because the increased steric hindrance at C-l causes C-2 nucleophilic addition to become competitive with C-l deprotonation. However, this problem can be overcome by the use of lithium tov-butoxide or lithium isopropoxide. This is shown for the achiral. V-allylketene A. O-aceta] precursor 8. 

The use of sugar-derived dioxanes (e.g. (69)) as chiral auxiliaries in Claisen rearrangements with optically pure substrates has been investigated by Tadano et al. (Equation (32)) <90JOC2108>. 

NAP-MgO acts as a bifunctional heterogeneous catalyst for the Claisen-Schmidt condensation (CSC) of benzaldehydes with acetophenones to yield chalcones, followed by asymmetric epoxidation (AE) to afford chiral epoxy ketones in moderate to good yields and impressive enantioselectivities (ee s). NAP-MgO, in combination with the chiral auxiliary (11 ,21 )-(- -)-1,2-diphenyl-1,2-ethylenediamine (DPED), catalyzed the asymmetric Michael addition of malonates to cyclic and acyclic enones. 

Chiral Auxiliary Mediated Asymmetric Ireland-Claisen Rearrangements 4.6.6.1 Chiral Clycolates... 

To date the most general chiral auxiliary mediated asymmetric Ireland-Claisen rearrangement is that of Corey et al. (Scheme 4.44) [47]. They found that treatment of crotyl propionates and related esters afforded good yields, diastereoselectivities and enantioselectivities of the pentenoic acid products. The rearrangements also occurred at significantly lower temperature than the silyl ketene acetals. A key advantage of the chemistry is that the chiral auxiliary attachment, Ireland-Claisen rearrangement, and auxiliary removal all occur in one pot. 

The search for a single structural motif to serve as a chiral auxiliary for the diversity of examples of the aza-Claisen rearrangement continues to produce some advancement. The prolinol derivative 412, oxazoline derivative 416, and (i )-l-phenylethanamine derivative "" 419 have been utilized to provide moderate to good asymmetric induction in specific cases as exemplified below. 

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