Biaryl lactones reduction

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]. 

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. ... 

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 5.11 Reductions of biaryl lactones with BINAL-H and CBS reagent.

The strategy based on the lactone concept is not restricted to biaryl lactones as substrates, but can be applied to other configurationally unstable biaryls such as biaryl hydroxy aldehydes. As an example, the reduction of biaryl hydroxy aldehydes in the presence of a CBS catalyst and catecholborane yielded the corresponding alcohols, as shown in Scheme 5.21. ... 

Bringmann and co-workers have reported highly efficient atropo-enantioselective reduction using OABs as chiral inducers to give one atropisomer with high enantiose-lectivities [76]. For example, the reduction of biaryl lactones 51 with BH3 THF (4 equiv.) in the presence of 2b (3 equiv.) in THF at 30 °C provided chiral biaryl alcohol 52 with up to 97% ee (Scheme 11.15). 

Scheme11.15 OAB-induced atropo-enantioselective reduction of biaryl lactones.

In a particularly striking example of the broad applicability of OAB methodology, racemic ketones and biaryl lactones have been resolved kinetically to provide the corresponding ketones and lactones with high enantioselectivities [77-79]. Reduction of a racemic ketone 53 using ent-2b- BHj (0.6 equiv.) in THF at -78 C for 30 min provided (-t)-54 in 38% yield, leaving unchanged (-)-53 with 89% ee in 40% yield (Scheme 11.16) [77]. Reduction of racemic ketone 55 under identical conditions, followed by oxidation of each of the product chiral alcohols 56 with PCC, provided (-)-55 (98% ee) and (+)-55 (82% ee) [78]. Similarly, kinetic resolution of racemic 7-mem-bered biaryl lactone 57 with BH3-THF (4.0 equiv.) in the presence of 2b (3.0 equiv.) in THF at -20 C provided (-t )-57 (87% ee, 46% yield) (79). 

Scheme 17.76 Kinetic resolution of racemic ketones and biaryl lactones via 2b-induced enantioselective reduction.

Acid treatment of a 3 1 mixture of murrayafoline A (7) and koenoline (8) led to chrestifoline A (192) in 70% yield. Addition of murrayafoline A (7) to a mixture of 1057 and lithium aluminum hydride in ether and dichloromethane afforded bismurrayafoline-A (197) in 19% yield (662) (Scheme 5.166). In addition to the aforementioned methods, the same group also reported a stereoselective synthesis of axially chiral bis-carbazole alkaloids by application of their "lactone concept" (663) and a reductive biaryl coupling leading to 2,2 -bis-carbazoles (664). 

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