Catalytic Enantioselective Cyanosilylation Research Articles

Chiral Lithium Salts of Phosphoric Acids as Lewis Acid–Base Conjugate Catalysts for the Enantioselective Cyanosilylation of Ketones

AbstractThe catalytic enantioselective cyanosilylation of aromatic ketones was developed by using chiral lithium salts of (R)‐BINOL‐ or (S)‐BINAM‐derived phosphoric acid compounds. In the presence of 10 mol% of chiral conjugate lithium salts, the corresponding tertiary cyanohydrins were obtained in high yields with moderate to high enantioselectivities. This is the first efficient example of asymmetric catalysis using lithium salts of synthetically useful chiral phosphoric acid compounds. A possible catalytic mechanism and transition states are also discussed as a preliminary working hypothesis.

Catalyst-Controlled Asymmetric Synthesis of Fostriecin and 8-epi-Fostriecin

Catalytic asymmetric synthesis of the natural antibiotic fostriecin (CI-920) and its analogue 8-epi-fostriecin and evaluation of their biological activity are described. We used four catalytic asymmetric reactions to construct all of the chiral centers of fostriecin and 8-epi-fostriecin; cyanosilylation of a ketone, Yamamoto allylation, direct aldol reaction, and Noyori reduction, two of which were developed by our group. Catalytic enantioselective cyanosilylation of ketone 13 produced the chiral tetrasubstituted carbon at C-8. Both enantiomers of the product cyanohydrin were obtained with high enantioselectivity by switching the center metal of the catalyst from titanium to gadolinium. Yamamoto allylation constructed the C-5 chiral carbon in the alpha,beta-unsaturated lactone moiety. A direct catalytic asymmetric aldol reaction of an alkynyl ketone using LLB catalyst constructed the chirality at C-9 with the introduction of a synthetically versatile alkyne moiety, which was later converted to cis-vinyl iodide, the substrate for the subsequent Stille coupling for the triene synthesis. Noyori reduction produced the secondary alcohol at C-11 from the acetylene ketone 6 with excellent selectivity. Importantly, all the stereocenters were constructed under catalyst control in this synthesis. This strategy should be useful for rapid synthesis of stereoisomers of fostriecin.

Power of Cooperativity: Lewis Acid—Lewis Base Bifunctional Asymmetric Catalysis

AbstractFor Abstract see ChemInform Abstract in Full Text.

Catalytic Enantioselective Synthesis of Key Intermediates for Triazole Antifungal Agents

[reaction: see text] A short-step synthesis of versatile chiral building blocks for triazole antifungal agents such as ZD0870 and Sch45450 was developed via catalytic enantioselective cyanosilylation of electron-deficient ketones as the key step. High enantioselectivity was produced using a catalyst prepared from Gd(HMDS)(3) and ligand 5 in a 2:3 ratio. This new catalyst preparation method was superior to the previous method using Gd(O(i)Pr)(3) as a metal source. A rationale for the difference is proposed on the basis of structural studies of the catalyst complexes using ESI-MS.

Power of Cooperativity: Lewis Acid-Lewis Base Bifunctional Asymmetric Catalysis

The concept of bifunctional asymmetric catalysis is very powerful for designing new enantioselective catalysts. We describe our investigation starting with the development of a BINOL-derived Lewis acid-Lewis base bifunctional asymmetric catalyst for cyanosilylation of aldehydes. The initial establishment of the concept was followed by the development of new sugar-derived catalysts that promote general catalytic enantioselective cyanosilylation of ketones. We also describe the catalytic enantioselective Reissert reaction of pyridine derivatives and Strecker reaction of ketoimines as recent advances in this field.

Catalytic Asymmetric Synthesis of (S)‐Oxybutynin and a Versatile Intermediate for Antimuscarinic Agents.

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Catalytic asymmetric synthesis of ( S)-oxybutynin and a versatile intermediate for antimuscarinic agents

A practical synthesis of ( S)-oxybutynin, a muscarinic receptor antagonist, using catalytic enantioselective cyanosilylation of cyclohexyl phenyl ketone ( 9a ) as a key step is described. The key reaction proceeded with 94% ee using 1 mol% of Gd- 1 catalyst, and was performed on a 100 g-scale. In addition, a short catalytic enantioselective synthesis of the versatile intermediate for Scios Nova analogues of antimuscarinic agents ( 7 ) is described. Application of the catalytic enantioselective cyanosilylation to ketones containing two sterically similar substituents on the carbonyl group is also discussed.

Practical synthesis of chiral ligands for catalytic enantioselective cyanosilylation of ketones and ketoimines.

A practical synthesis of chiral ligands that are useful for catalytic enantioselective cyanosilylation of ketones and ketoimines is described. Compared with the previous synthetic route, the number of total steps is decreased and the total yield is greatly improved. Furthermore, both (+)- and (-)-ligands are readily available by this new synthetic route.

A Practical Synthesis of (S)‐Oxybutynin.

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Recent Progress in Asymmetric Two‐Center Catalysis

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Catalytic Enantioselective Synthesis of (20S)-Camptothecin Intermediates Using Cyanosilylation of Ketones Promoted by D-Glucose-derived Lanthanide Catalyst

An efficient catalytic enantioselective synthetic route was developed for Curran's versatile camptothecin intermediate (5). The key step is the catalytic enantioselective cyanosilylation of ketone (7) using a chiral samarium (Sm) complex. The target ketone cyanohydrin (6) was obtained with 90% ee using 2 mol % of the catalyst. A gadolinium (Gd) complex derived from the same chiral ligand could also be used as an enantioselective catalyst to synthesize Corey's intermediate (11).

A practical synthesis of ( S)-oxybutynin

( S)-Oxybutynin, an important drug acting as muscarinic receptor antagonist, was practically synthesized using catalytic enantioselective cyanosilylation of cyclohexyl phenyl ketone ( 6a ) as a key step. Cyanohydrin 7a with 94% ee was obtained with 1 mol% of Gd- 5 catalyst. The key α-hydroxy carboxylic acid 8 was synthesized from 7a in an enantiomerically pure form without column chromatography. Other cycloalkyl phenyl ketones, except cyclopentyl phenyl ketone ( 6e-H ) gave products with high enantioselectivity. The enantioselectivity of the reaction of 6e was dramatically improved using α-deuterium substituted 6e-D . The dramatic deuterium effect provides an important insight into the competitive reaction pathway.

ChemInform Abstract: Practical Synthesis of Chiral Ligands for Catalytic Enantioselective Cyanosilylation of Ketones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Studies Toward Practical Synthesis of (20S)‐Camptothecin Family Through Catalytic Enantioselective Cyanosilylation of Ketones: Improved Catalyst Efficiency by Ligand‐Tuning.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Recent progress in asymmetric two-center catalysis.

Recent progress using two types of enantioselective two-center catalysts, Lewis acid-Brönsted base and Lewis acid-Lewis base bifunctional complexes, is described. The first part of this review discusses improvements in the syn-selective direct catalytic enantioselective aldol reaction and 1,4-addition reaction of a 2-hydroxyacetophenone derivative using a Zn-linked-BINOL complex. In the second part, we describe the development of catalysts displaying Lewis acidity and Lewis basicity in a catalytic enantioselective cyanosilylation of aldehydes and the logical extension to a tetrasubstituted carbon synthesis through a Reissert-type reaction and a cyanosilylation of ketones.

Practical synthesis of chiral ligands for catalytic enantioselective cyanosilylation of ketones

A practical and more environmentally benign synthetic route of chiral ligands that are useful for catalytic enantioselective cyanosilylation of ketones is described. A key step is the regioselective S N2 reaction to cyclic sulfate 12 with catechol derivatives. A range of chiral ligands containing electronically tuned catechols has become available by this new route.

Studies toward practical synthesis of (20 S)-camptothecin family through catalytic enantioselective cyanosilylation of ketones: improved catalyst efficiency by ligand-tuning

Enantioselective catalyst efficiency for the synthesis of the camptothecin family was improved through ligand-tuning. Key intermediates of two convergent syntheses of camptothecin (Curran's intermediate and Corey's intermediate) were obtained in up to 10 g scale through the catalytic enantioselective cyanosilylation of ketones.

ChemInform Abstract: Catalytic Enantioselective Cyanosilylation of Ketones: Improvement of Enantioselectivity and Catalyst Turn‐Over by Ligand Tuning.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Catalytic enantioselective cyanosilylation of ketones: improvement of enantioselectivity and catalyst turn-over by ligand tuning

Sterical and electronical tuning of the bifunctional catalyst 1 afforded the improved catalyst 2 , which promoted the cyanosilylation of ketones with higher enantioselectivity as well as with improved catalyst turn-over with a factor of up to 10. Thus, chiral quaternary α-hydroxynitriles were obtained with excellent ee (up to 94% ee) using 1 mol% of 2 in the case of aryl ketones and 2.5 mol% of 2 in the case of aliphatic ketones.

Multifunctional asymmetric catalysis.

Two types of general and practical enantioselective catalysts, namely, bimetallic complexes and Lewis acid-Lewis base bifunctional catalysts were developed based on the concept of multifunctional catalysis. In the first part of this review, the first example of a catalytic enatioselective nitro-Mannich reaction as well as a direct catalytic enantioselective aldol reaction of 2-hydroxyacetophenone using bimetallic complexes is discussed. The new complex, composed of ytterbium, potassium, and BINOL in a ratio of 1:1:3, promoted the nitro-Mannich reaction of nitromethane with up to 91% ee. On the other hand, second generation ALB catalyzed an enantioselective and diastereoselective nitro-Mannich reaction of nitroalkanes in up to 83% ee with a diastereomeric ratio up to 7:1. Moreover, the reaction of aldehydes with 2-hydroxyacetophenone in the presence of LLB, KHMDS, and H2O selectively gave the corresponding anti-alpha,beta-dihydroxy ketones in up to 95% ee and, in the presence of the catalyst prepared from linked-BINOL and 2 eq of Et2Zn, selectively afforded the syn-alpha,beta-dihydroxy ketones in up to 86% ee. In the second part, the development of new catalysts displaying a Lewis acidity and a Lewis basicity is described. The Lewis acid of the catalyst activates aldehydes, imines, acyl quinoliniums, and ketones. At the same time, the Lewis base activates the nucleophile (TMSCN). Catalysts of this type produced a highly enantioselective cyanation of these electrophiles. Application of the catalytic enantioselective cyanosilylation of aldehydes to a total synthesis of epothilones is also described.