Catalytic Asymmetric Synthesis. Группа авторов

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Scheme 1.5. The reaction mechanism.

Nishibayashi reported an enantioselective propargylic alkylation of propargylic alcohols with aldehydes in the presence of a thiolate‐bridged diruthenium complex and diarylprolinol silyl ether as a co‐catalyst to afford the corresponding propargylic alkylated products in excellent yields with high enantioselectivity (Eq. 1.46) [78]. This is a new type of enantioselective propargylic substitution reaction, wherein the chiral enamines react with the ruthenium–allenylidene complexes, where both the transition metal catalyst (ruthenium complex) and organocatalyst (secondary amine) activate propargylic alcohols and aldehydes, respectively, and cooperatively.

(1.46)

       1.7.2.2. Iminium Ion and Transition Metal Catalyst

Cordova reported an enantioselective silyl addition to enals using Me₂PhSi‐B(pin) as a silyl source, and the reaction is catalyzed by a combination of diphenylprolinol silyl ether and a copper(I) salt (Eq. 1.47) [79]. The copper(I)–silyl intermediate is a nucleophile that reacts with an iminium ion to afford the Michael product with excellent enantioselectivity. The product is a synthetically useful β‐silylated aldehyde.

(1.47)

The same group extended the reaction using B₂ (pin)₂ and dialkyl zinc, respectively, by a combined use of diphenylprolinol silyl ether and Cu(OTf)₂ to afford β‐borylated aldehydes (Eq. 1.48) [80] and β‐alkylated aldehydes [81], respectively, both with excellent enantioselectivity. The β‐arylation reaction also proceeded using ArB(OH)₂, which is catalyzed by diphenylprolinol silyl ether and Pd(OAc)₂ [82].

(1.48)

It is known that Hantzsch esters are useful hydride donors for the reduction of α,β‐unsaturated aldehydes to saturated aldehydes, and, in 2005, MacMillan reported the asymmetric reduction of β,β‐disubstituted α,β‐unsaturated aldehydes catalyzed by MacMillan’s catalyst (Eq. 1.49) [83].

In 2012, Hori reported an asymmetric hydrogenation of β,β‐disubstituted α,β‐unsaturated aldehyde, which is catalyzed by a combination of 2‐diarylmethylpyrrolidines and heterogeneous Pd/BaSO₄ under an H₂ atmosphere (Eq. 1.50) [84]. This reaction is successfully applied to citral. A mixture of E‐ and Z‐citral in any ratio afforded citronellal with high enantioselectivity. Citronellal is a key synthetic intermediate of l‐menthol.

(1.49)

(1.50)

      1.7.3. Two Chiral Catalysts

      In the synthesis of molecules with two chiral centers, there are four possible isomers. When one chiral catalyst controls one chiral center and the second chiral catalyst controls the second chiral center independently with minimal matched/mismatched interactions, all four isomers can be synthesized with high selectivity. However, the realization of this concept is very difficult. Recently, excellent catalyst systems have been reported for this type of the reaction.

Carreira reported a stereodivergent α‐allylation of branched aldehydes by the reaction of allylic alcohols and α,α‐disubstituted acetaldehydes (Scheme 1.6) [85]. Products bearing quaternary stereocenters in a vicinal relationship to tertiary stereocenters are obtained in good yields with excellent selectivities. Cinchona‐alkaloid‐derived primary amine (A1 and A2) and chiral iridium (ligand: L) were used as catalysts. The amine catalyst reacts with an aldehyde to generate an enamine, which controls the enantioface selectivity of the aldehyde, while iridium catalyst generates a chiral π‐allyl complex in which two distinct and highly face‐selective catalytic cycles are merged to provide access to all possible stereoisomers of a target compound in enantiomerically pure form.

      The author also extended this reaction to the stereodivergent α‐allylation of linear aldehydes with dual chiral iridium catalyst and diphenylprolinol silyl ether catalyst [86].

Dong reported a stereodivergent synthesis of γ,δ‐unsaturated aldehydes via alkyne hydrofunctionalization starting from α‐branched aldehydes and alkynes using Rh catalyst with a chiral bisphosphine ligand (L) and a chiral primary amine catalyst (A) (Scheme 1.7) [87]. An alkyne isomerizes into an allene by Rh catalyst and it is further converted into π‐allyl Rh complex with a chiral ligand. Chiral amine reacts with an aldehyde to generate a chiral enamine, which reacts with a chiral π‐allyl Rh complex. All possible stereoisomers were obtained with high enantio‐, diastereo‐, and regioselectivity.

Scheme 1.6. Stereodivergent α‐allylation of branched aldehydes using allyl alcohols.

      Source: [85]/American Association for the Advancement of Science.