Biaryl lactone

ASYMMETRIC SYNTHESIS OF (M)-2-HYDROXYMETHYL-1-(2-HYDROXY-4,6-DIMETHYLPHENYL)NAPHTHALENE VIA A CONFIGURATIONALLY UNSTABLE BIARYL LACTONE... 

Dahl and Branchaud [36] synthesized a biaryl lactone 17 derived from a hydroxy-diacid, that should be able to act as a molecular motor by passing through... 

Fig. 5 Scheme of the functioning of a molecular motor based on a biaryl lactone. Only (S)-17 and its derivatives are shown, although in practice racemic 17 has been used and 18, 19, and 20 are racemic as well. C(C6H5)(CH3)2NH2 was used as a nucleophile (Nu = C(C6H5)(CH3)2NH) in the presence of A1(CH3)3. The lactonization of 19 to 20 was done with DCC, DMAP, and DMAP HC1... 

Dahl BJ, Branchaud BP (2006) 180° unidirectional bond rotation in a biaryl lactone artificial molecular motor prototype. Org Lett 8 5841-5844... 

Lin Y, Dahl BJ, Branchaud BP (2005) Net directed 180° aryl-aryl bond rotation in a prototypical achiral biaryl lactone synthetic molecular motor. Tetrahedron Lett 46 8359-8362... 

Bringmann, G. Menche, D. Stereoselective Total Synthesis of Axially Chiral Natural Products via Biaryl Lactones, Acc. Chem. Res. 2001,34,615-624. 

Bringman et al. have investigated biaryl lactones and biaryl thionolactones as precursors to enantiomerically enriched axially chiral biaryls. Both, the lactones and the thionolactones are configurationally labile. In this method, biaryl products are obtained by coordination of a Lewis acid followed by reductive lactone ring cleavage. Asymmetric induction requires either the Lewis acid or the reducing agent to be chiral. Both approaches have been realized for biaryl thionolactones with mild Ru Lewis acids (Scheme 10.18) [29]. 

One means of stereoselective cleavage of biaryl lactones [53] is activation of the carbonyl group with a Lewis acid and subsequent attack with a chiral nucleophile. Conversely, activation can be effected with a chiral Lewis acid followed by attack of an achiral nucleophile. Complexation of a biaryl lactone to the chiral fragment [CpRe (NO)(PPh3)j then reduction with K(s-Bu)3BH (K-selectride) and ring opening of the intermediate rhenium lactolate gives the metalated aldehyde (dr = 75 25) which is converted to the alcohol without essential loss of optical purity (Sch. 6) [54]. 

An efficient atropo-enantioselective total synthesis of the axially chiral bicoumarin (+)-isokotanin was accomplished by J. Bringmann and co-workers.The key steps in this synthetic approach were the formation of a configurationally stable seven-membered biaryl lactone by the Cannizzaro reaction of the corresponding biaryl dialdehyde followed by a kinetic resolution by atroposelective ring cleavage. 

Bringmann, G., Hinrichs, J., Henschel, P., Kraus, J., Peters, K., Peters, E.-M. Novel concepts in directed biaryl synthesis, 97. Atropo-enantioselective synthesis of the natural bicoumarin (+)-isokotanin A via a configurationally stable biaryl lactone. Eur. J. Org. Chem. 2002, 1096-1106. 

Bringmann G, Menche D (2001) Stereoselective total synthesis of axially chiral natural products via biaryl lactones. Acc Chem Res 34 615-624... 

The possibihty of chiral modiflcation of NaBH4 for reduction of ketones has been scrutinized. Some success is reported by adding the inexpensive cychc borinate 183 derived from tartaric acid and PhB(OH)2 to the reaction medium. Atropo-enantioselective reduction of biaryl lactones occurs on exposure to NaBH in the presence of the cobalt chelate 184. ... 

Stereoselective total synthesis of axially chiral natural products via biaryl lactones 01ACR615. 

Our first synthetic approach was performed racemically by reducing a biaryl lactone intermediate to a diol, with an eye toward applying Bringmann s method to achieve an asymmetric synthesis (Scheme 10). First, iodination of 3,4,5-trimethoxybenzoic acid followed by DCC coupling with 3,4,5-trimethoxyphenol 22 provided aryl halobenzoate ester... 

By modification of the reaction condition, biaryl lactones could be efficiently reduced to the corresponding biaryl products by this cobalt-catalyzed system. Various axially chiral biaryl compounds were obtained with high ee values (80-93% ee) by the atmpo-enantioselective borohydride reduction with the dynamic kinetic resolution of biaryl lactones in the presence of EtOH and l-(2-pyridinyl)ethanol (eq 39). 

Scheme 5.3 Three possibilities for the metal-assisted ring opening of biaryl lactones.

Scheme 5.5 Alcoholysis of biaryl lactones with metallated (if)-menthoxides.

Scheme 5.6 Alcoholysis of biaryl lactones with sodium (/ )-menthoxides.

Scheme 5.8 Alcoholysis of biaryl lactone with (rPrO)2Ti-TADDOLate.

The first successful approach to a directly enantioselective variant of the method was achieved with Seebach s (r Pr)2Ti-TADDOLate, which served both as a chiral Lewis acid and as the O-nucleophile (Scheme 5.8). This titanium complex reacted with a biaryl lactone, yielding the corresponding ester with a moderate selectivity. ... 

The reaction of biaryl lactones with C-nucleophiles was interesting since it allowed an extension of the carbon framework. For the condensation of the chiral lithiated sulfoxide depicted in Scheme 5.10, a 1 1 mixture of the two diastereomeric /i-ketosulfoxides was formed due to the interconversion of the... 

On the other hand, it was possible to cleave the biaryl lactones with chiral hydride transfer reagents, such as Noyori s BINAL-H, or borane THF in the presence of Corey-Bakshi-Shibata (CBS) reagent, furnishing the corresponding alcohols in excellent yields and enantioselectivities, as shown in Scheme 5.11. 

In another context, the biaryl lactones could also be activated by a tf-coordination of a transition metal fragment which added an additional element of planar chirality to the system. For instance, coordination of a tricarbonyl chromium unit to the phenolic part of biaryl lactones delivered the corresponding jj -complex. The latter complex was configurationally unstable and existed as a mixture of the two atropodiastereomeric forms. From this equilibrium, the ring cleavage with sodium borohydride proceeded highly stereo-selectively, yielding the biaryl alcohol exo complex exclusively (Scheme 5.12). ... 

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