Chiral Lewis Acid Catalyst Research Articles

Air‐Stable, Storable, and Highly Selective Chiral Lewis Acid Catalyst.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Highly Enantioselective 1,3-Dipolar Cycloaddition Reaction in Alcoholic Media: Ni(II)-Pybox-tipsom Catalyst.

Abstract From the viewpoint of environmentally friendly reaction conditions, catalytic asymmetric nitrone 1,3-dipolar cycloaddition (DC) reactions in protic media have been investigated. DC reaction of nitrones with alkenoyl oxazolidinone and pyrrolidinone derivatives in t -BuOH in the presence of sterically tuned bis(oxazolinyl)pyridine (pybox- tipsom 1d ) and Ni(II) complex as a chiral Lewis acid catalyst proceeded smoothly to give the corresponding cycloadducts ranging from 90:10 to >99:1 of endo / exo ratio and ranging from 90 to 98% ee for the endo adduct. The use of sterically hindered alcohols such as t -BuOH and s -BuOH as a non-halogenated solvent was shown to effect rate acceleration for the DC reaction compare to CH 2 Cl 2 at the same temperature. Furthermore, no solvolysis products of nitrones and cycloadducts were observed in these protic media despite the possible formation of Bronsted acid.

Enantioselective Michael addition reactions of malononitrile catalyzed by chiral Lewis acid and achiral amine catalysts

Reactions of malononitrile with 3-(2-alkenoyl)-2-oxazolidinones or 1-(2-alkenoyl)-4-bromo-3,5-dimethylpyrazoles can be doubly activated by the use of catalytic amounts (10 mol% each) of both ( R, R)-DBFOX/Ph·Ni(ClO 4) 2·3H 2O and amines, to give the Michael adducts in high chemical yields with satisfactory enantioselectivities.

Enantioselective Michael Additions of Nitromethane by a Catalytic Double Activation Method Using Chiral Lewis Acid and Achiral Amine Catalysts.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Acceleration Effect of Lewis Acid in Allylboration of Aldehydes: Catalytic Regiospecific, Diastereospecific, and Enantioselective Synthesis of Homoallyl Alcohols.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Bis(((S)-binaphthoxy)(isopropoxy)titanium) oxide as a mu-oxo-type chiral Lewis acid: application to catalytic asymmetric allylation of aldehydes.

A new, chiral bis-Ti(IV) oxide of type 1 was successfully designed and can be utilized for strong activation of aldehyde carbonyls, thereby allowing a new catalytic enantioselective allylation of aldehydes with allyltributyltin. The chiral bis-Ti(IV) catalyst (S,S)-1 can be readily prepared either by treatment of bis(triisopropoxy)titanium oxide with (S)-binaphthol or by reaction of ((S)-binaphthoxy)isopropoxytitanium chloride with silver(I) oxide. Reaction of hydrocinnamaldehyde with allyltributyltin (1.1 equiv) under the influence of in situ generated chiral bis-Ti(IV) oxide (S,S)-1 (10 mol %) in CH2Cl2 at 0 degrees C for 4 h afforded 1-phenyl-5-hexen-3-ol in 84% yield with 99% ee. The present asymmetric allylation using nonracemic bis-Ti(IV) oxide 1 with partially resolved (S)-binaphthol exhibits a positive nonlinear effect in correlating the enantiopurity of allylation product with the ee of (S)-binaphthol. This asymmetric approach provides a very useful way for obtaining high reactivity and selectivity by the simple introduction of the M-O-M unit in the design of chiral Lewis acid catalysts.

Asymmetric Diels—Alder Reactions Catalyzed by Chiral Ni(II)‐Binaphthyldiimine Complexes.

Ni(II)-N,N′-Bis(2-quinolylmethylene)-1,1′-binaphthyl-2,2′-diamine complex was found to be an efficient chiral Lewis acid catalyst for asymmetric Diels–Alder reactions (endo: up to 94% ee) between cyclopentadiene (1) and 3-alkenoyl-2-oxazolidinones (2). In the presence of Ni(II) catalyst (1 mol%), the reaction between cyclopentadiene and 3-acryloyl-2-oxazolidinone proceeded smoothly (85% yield) at −40 °C with high enantioselectivity (endo: 90% ee).

New bulky chiral Lewis acid catalyst: 3,3'-di(2-mesitylethynyl)binaphthol-titanium(IV) complex.

A new chiral Lewis acid catalyst 9 was prepared in situ from a 1:2 molar mixture of (R)-3,3'-di(2-mesitylethynyl)binaphthol (6) and titanium(IV) isopropoxide at ambient temperature. The 3- and 3'-substituents on 6 were effective for preventing undesired aggregation between Ti(IV) complexes and increasing the enantioselectivity (up to 82% ee) in the Diels-Alder reaction of methacrolein with cyclopentadiene.

Novel Asymmetric Michael Addition of α‐Cyanopropionates to Acrolein by the Use of a Bis(oxazolinyl)phenylstannane‐Derived Rhodium(III) Complex as a Chiral Lewis Acid Catalyst.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Highly enantioselective 1,3-dipolar cycloaddition reactions of 2-benzopyrylium-4-olate catalyzed by chiral Lewis acids.

We have found that significant levels of enantioselectivity are obtained in the 1,3-dipolar cycloadditions of 2-benzopyrylium-4-olate using chiral 2,6-bis(oxazolinyl)pyridine (Pybox)-rare earth metal triflate complexes as chiral Lewis acid catalysts. The reactions with benzyloxyacetaldehyde derivatives catalyzed by Sc(III)-Pybox-i-Pr (10 mol %) proceeded to give endo-adducts selectively with high enantioselectivity (up to 93% ee). The reaction with benzyl pyruvate under similar conditions gave an exo-adduct selectively with 87% ee. In the reaction with 3-acryloyl-2-oxazolidinone, Yb(III)-Pybox-Ph was found to be effective in providing an exo-adduct with extremely high enantioselectivity (98% ee).

Novel chiral gallium Lewis acid catalysts with semi-crown ligands for aqueous asymmetric Mukaiyama aldol reactions

Asymmetric Mukaiyama aldol reactions in aqueous media (water-ethanol = 9:1) were catalyzed by chiral gallium catalysts with semi-crown ligands to give aldol products with good yields, syn-diastereoselectivities and enantioselectivities.

(R)‐2,2′‐Bis(stannyl)‐1,1′‐binaphthyls as a New Chiral Bis‐metallic Binaphthyl Catalyst.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Enantioselective Michael additions of nitromethane by a catalytic double activation method using chiral lewis Acid and achiral amine catalysts.

Reactions of nitromethane with 1-(2-alkenoyl)-3,5-dimethylpyrazoles can be effectively catalyzed by R,R-DBFOX/Ph.Ni(ClO4)2.3H2O and achiral amine bases, each in a catalytic loading of 10 mol %, to give 1-(3-substituted 4-nitrobutanoyl)-3,5-dimethylpyrazoles in high chemical yields. Excellent enantioselectivities up to 98% ee have been achieved. The nitro moiety can be easily reduced on Raney nickel at atmospheric pressure, followed by concurrent cyclization, to give enantiomers of 4-substituted 2-pyrrolidinone derivatives after usual workup. This method can be successfully applied to a short step synthesis of (R)-(-)-rolipram.

A highly enantioselective 1,3-dipolar cycloaddition reaction in alcoholic media: Ni(II)-pybox-tipsom catalyst

From the viewpoint of environmentally friendly reaction conditions, catalytic asymmetric nitrone 1,3-dipolar cycloaddition (DC) reactions in protic media have been investigated. DC reaction of nitrones with alkenoyl oxazolidinone and pyrrolidinone derivatives in t-BuOH in the presence of sterically tuned bis(oxazolinyl)pyridine (pybox-tipsom1d) and Ni(II) complex as a chiral Lewis acid catalyst proceeded smoothly to give the corresponding cycloadducts ranging from 90:10 to >99:1 of endo/exo ratio and ranging from 90 to 98% ee for the endo adduct. The use of sterically hindered alcohols such as t-BuOH and s-BuOH as a non-halogenated solvent was shown to effect rate acceleration for the DC reaction compare to CH2Cl2 at the same temperature. Furthermore, no solvolysis products of nitrones and cycloadducts were observed in these protic media despite the possible formation of Brønsted acid.

Acceleration effect of Lewis acid in allylboration of aldehydes: catalytic, regiospecific, diastereospecific, and enantioselective synthesis of homoallyl alcohols.

The addition of pinacol allylboronic esters to aromatic and aliphatic aldehydes smoothly occurred at -78 degrees C in toluene in the presence of a catalytic amount of AlCl3 or Sc(OTf)3 (10 mol %) to give the corresponding homoallyl alcohols in high yields. The reactions proceeded regio- and diastereospecifically, yielding the isomerically pure syn- and anti-homoallyl alcohols from (Z)- and (E)-allylboronic esters, respectively. The protocol was also applied to enantioselective reactions by using a chiral Lewis acid catalyst.

Asymmetric Diels–Alder Reactions Catalyzed by Chiral Ni(II)-Binaphthyldiimine Complexes

Abstract Ni(II)-N,N′-Bis(2-quinolylmethylene)-1,1′-binaphthyl-2,2′-diamine complex was found to be an efficient chiral Lewis acid catalyst for asymmetric Diels–Alder reactions (endo: up to 94% ee) between cyclopentadiene (1) and 3-alkenoyl-2-oxazolidinones (2). In the presence of Ni(II) catalyst (1 mol%), the reaction between cyclopentadiene and 3-acryloyl-2-oxazolidinone proceeded smoothly (85% yield) at −40 °C with high enantioselectivity (endo: 90% ee).

Air-stable, storable, and highly selective chiral Lewis acid catalyst.

An air-stable, storable, and highly selective chiral Lewis acid catalyst for asymmetric Mannich-type reactions has been developed. The catalyst can be stored for more than three months in air at room temperature without loss of activity. Moreover, it has also been demonstrated that the catalyst can be recovered and reused. [structure: see text]

Novel asymmetric michael addition of alpha-cyanopropionates to acrolein by the use of a bis(oxazolinyl)phenylstannane-derived rhodium(III) complex as a chiral Lewis acid catalyst.

The rhodium complex prepared in situ by simply mixing [[RhCl(c-octene)2]2] and [(Phebox)SnMe3] (1) (Phebox = 2,6-bis(oxazolinyl)phenyl) was found to serve as an efficient catalyst for the asymmetric Michael addition of alpha-cyanopropionates (4) to acrolein under mild and neutral conditions. In the present catalytic system, both the temperature of catalyst preparation and the order of the addition of the substrates were very important for the catalytic efficiency and enantioselectivity. Detailed mechanistic studies of this catalytic system revealed that the [(Phebox)RhIII(SnMe3)Cl] complex (9), generated by oxidative addition of [[RhCl(c-octene)2]2] to 1, is an active catalyst and the turnover number (TON) of the present actual catalyst existing in a reaction mixture is greater than 10,000. The obtained (R) stereochemistry of the Michael adducts 5 can be explained by N-bonded enol intermediates C', which are formed by enolization of 4 bound to the Lewis acidic rhodium complex 9. We also found that the active catalyst 9 gradually decomposed in the presence of the remaining [[RhCl(c-octene)2]2] in the reaction mixture to form the catalytically nonactive [(Phebox)RhCl2] fragment A, whose structure was characterized by an X-ray crystallographic study after converting to the tBuNC complex 10.

(R)-2,2′-Bis(stannyl)-1,1′-binaphthyls as a New Chiral Bis-Metallic Binaphthyl Catalyst

Abstract Dilithiation followed by bis-stannylation with Me3SnCl of (R)-2,2′-dibromo-1,1′-binaphthyl (2) and the subsequent redistribution reaction of resulting (R)-2,2′-bis(trimethylstannyl)-1,1′-binaphthyl (6) with SnCl4 gave the novel chiral Lewis acid catalyst (R)-2,2′-bis(dichloromethylstannyl)-1,1′-binaphthyl (4). The catalytic properties of 4 and its triflate 5 were investigated as the first chiral bis-metallic binaphthyl catalyst.

Catalytic Enantioselective Diels-Alder Reactions: Methods, Mechanistic Fundamentals, Pathways, and Applications

One hundred years after the birth of Kurt Alder and seventy-five years after the discovery of his famous reaction, one of the most important and fascinating transformations in chemistry, research on that process continues to surprise, excite, delight, and inform the chemical community. This article is based on presentations given first at the University of Cologne, Germany (Kurt Alder lecture, 1992), then at the Roger Adams Award Symposium (1993), and later at the Bürgenstock Conference of 2001, and describes research by our group on the development and understanding of enantioselective versions of the Diels-Alder reactions. The elements of this review include (1) development of new chiral Lewis acid catalysts for highly enantioselective (>25:1) [4+2] cycloadditions; (2) the fine mechanistic details and pre-transition-state assemblies of these reactions; (3) the fundamental understanding of catalytic activity and enantioselectivity for highly enantioselective Diels-Alder processes; and (4) applications to the synthesis of complex molecules. The range and power of the Diels-Alder reaction have steadily increased over seven decades. The end of this remarkable development is not in sight, a high compliment to this field of Science and to its great inventor.