Читать книгу Catalytic Asymmetric Synthesis - Группа авторов - Страница 62

In order to attain high enantioselectivity, numerous kinds of chiral Brønsted acids were developed. Regarding CPA, bulky 3,3′‐substituents such as 2,4,6‐triisopropylphenyl and 2,4,6‐tricyclohexylphenyl groups were introduced. In order to realize an extremely sterically demanding cavity, List designed and synthesized confined IDP 10a on the basis of a C₂‐symmetric imidodiphosphoric acid motif, and realized a highly enantioselective spiroacetalization (Scheme 2.73) [13]. Small and functionally unbiased substrates were found to be suitable because of the geometrically constrained bifunctional active site.

Scheme 2.73. Asymmetric spiroacetalization by confined Brønsted acid.

Source: Based on [13].

Nagorny concurrently reported spiroketalization using CPA 6e, although the use of tertiary alcohols was critical as substrates (Scheme 2.74) [159].

Scheme 2.74. Asymmetric spiroacetalization by TRIP.

Source: Based on [159].

Liu reported an intramolecular hydroamination of alkenes using chiral phosphoramide 34 to furnish pyrrolidines with an α‐tetrasubstituted carbon stereocenter (Scheme 2.75a) [160]. Liu subsequently applied the methodology for the desymmetrization of meso dienes to afford pyrrolidine derivatives bearing two congested tertiary or quaternary stereocenters based on the hydroamination of unactivated alkenes (Scheme 2.75b) [161]. Mechanistic study elucidated the transition state 35, wherein thiourea moiety was employed both as activating and a directing group through cooperative multiple hydrogen bonds with a Brønsted acid and the double bond.

Sun reported an asymmetric synthesis of 1,1‐diarylethanes through a transfer hydrogenation reaction of 1,1‐diarylalkenes bearing o‐hydroxyphenyl moieties and Hantzsch ester using 6i as shown in Scheme 2.72. Indole also participated in the reaction to afford 1,1,1‐triarylethanes bearing acyclic all‐carbon quaternary stereocenters using 13d (Scheme 2.76) [158].

Scheme 2.75. Intramolecular hydroamination of alkenes (a) (

Source: Based on [160]

), and its application to desymmetrization of meso dienes (b) (

Source: Based on [161]).

Scheme 2.76. Hydroarylation of 1,1‐diarylethenes.

Source: Based on [158].

Yamamoto reported a bromocyclization of polyenes using 1,3‐dibromo‐5,5‐dimethylhydantoin as the electrophilic bromine source and chiral phosphoramide 14g bearing bulk 4‐(9‐antrhyl)‐2,6‐diisopropylphenyl moiety at 3,3′‐position (Scheme 2.77) [162].

Ackermann reported the first example of the activation of unactivated alkene by CPA 6b. Intramolecular hydroamination reaction took place to furnish pyrrolidine derivative with 17% ee [163]. A highly enantioselective version of the intramolecular hydroalkoxylation of unactivated alkene was developed by List using confined and strong chiral Brønsted acid [164]. Tetrahydrofuran derivatives with the stereogenic center at 2‐position and tetrahydropyrans were obtained with 84–97% ee using 11m (Scheme 2.78b). List recently achieved an intramolecular hydroarylation of unactivated alkenes with indoles catalyzed by a strong and confined chiral Brønsted acid [165]. Both alkyl and aryl‐alkenes participated in the reaction successfully to construct a quaternary stereocenter with 68–94% ee using 11n (Scheme 2.78b).

Scheme 2.77. Bromocyclization of polyenes.

Source: Based on [162].

Scheme 2.78. Intramolecular hydroalkoxylation of unactivated alkenes (a) [164], and hydroarylation of unactivated alkenes (b) [165].