A chiral bidentate phosphoramidite (Me-BIPAM) for Rh-catalyzed asymmetric hydrogenation of α-dehydroamino esters, enamides, and dimethyl itaconate

High performance of Me-BIPAM for enantioselective hydrogenation of α-dehydroamino esters, enamides, and dimethyl itaconate was demonstrated. [Rh(Me-BIPAM)(diene)]X (diene = cod, nbd; X = BF₄, PF₆, SbF₆) gave optically active β-aryl α-amino esters up to 99% ee, 1-arylethylamines up to 97% ee, methyl 2-acetylaminobutanoate with 90% ee, and dimethyl 2-methylsuccinate with 97% ee under 0.3−0.8 MPa dihydrogen with 0.1−1 mol % catalyst loading.     

A novel class of amide-derived air-stable P,O-ligands for Suzuki cross-coupling at low catalyst loading

The benzamide-derived P,O-ligands efficiently promoted the Pd-catalyzed Suzuki cross-coupling reactions of aryl bromides with phenylboronic acid at 0.01 mol % of Pd loading at 60-80 °C to form biaryls in excellent yields. A sterically hindered arylboronic acid gave a quantitative yield of the coupling product at 110 °C with 1 mol % Pd.     

Dynamic kinetic resolution of hemiaminals using a novel DMAP catalyst

We describe the first catalytic dynamic kinetic resolution of hemiaminals mediated by an organocatalyst. A 0.1-1 mol % catalyst loading is effective for the dynamic kinetic resolution of hemiaminals to produce esters up to 88% ee in high yields. A 10 mol % catalyst loading resulted in a decreased selectivity, whereas the selectivity increased at 50 °C. The absolute configuration is assigned on the basis of the empirical Cotton effect rule.     

Enantioselective cyanosilylation of aldehydes catalyzed by a novel N,N′-dioxide-Ti(OPr)4 bifunctional catalyst

A novel bifunctional asymmetric catalyst containing N-oxide and titanium(IV) was developed and applied to the asymmetric cyanosilylation of aldehydes. Optically active trimethylsilyl cyanohydrin ethers were obtained up to 99% yield and 80% ee in the presence of 5 mol % catalyst loading at −78 °C. Based on the experimental results, the catalytic cycle was proposed as a pathway in which Lewis acid and Lewis base activated aldehyde and trimethylsilylcyanide (TMSCN), respectively.     

Dicationic (BINAP)palladium-catalyzed enantioselective aldol reaction of aldehydes with a silyl enol ether: a simplified practical procedure

The dicationic ((R)-BINAP)palladium-catalyzed enantioselective aldol reaction of benzaldehyde with 1-phenyl-1-trimethylsilylethene has been reinvestigated regarding the reaction conditions in the presence of ((R)-BINAP)palladium chloride and AgSbF₆ with 3 Å molecular sieves. The simplified practical procedure with 1 mol % catalyst loading realized the high performance of 98% yield and 76% ee with reliable reproducibility.     

Hydroxymethylation of α-substituted nitroacetates

Only 1 mol % of K₃PO₄ is efficient enough to catalyze the hydroxymethylation of α-substituted nitroacetates in good to excellent yield. Both aliphatic and aryl substituted nitroacetates work well under this reaction. The first catalytic asymmetric version of this reaction also reported that 10 mol % of cupreidine could catalyze this reaction up to 71% ee and 89% yield. Paraformaldehyde and formalin could both serve as the hydroxymethylation C1 unit. The synthetic application of products is also demonstrated.     

Highly enantioselective aza-Morita-Baylis-Hillman reaction with a bisphenol-based bifunctional organocatalyst

Newly developed phosphino-bisphenol 1c was found to be an efficient organocatalyst for the aza-Morita-Baylis-Hillman reaction. High enantioselectivity up to 96% ee was obtained with catalyst loading of 1 mol %.     

Ir-catalyzed asymmetric allylic alkylation using chiral diaminophosphine oxides: DIAPHOXs. Formal enantioselective synthesis of (−)-paroxetine

An Ir-catalyzed asymmetric allylic alkylation using chiral diaminophosphine oxide is described. Asymmetric allylic alkylation of terminal allylic carbonates proceeded using 5 mol % of Ir catalyst, 5 mol % of DIAPHOX 1i, 10 mol % of NaPF₆, 10 mol % of LiOAc, and N,O-bis(trimethylsilyl)acetamide (BSA), affording the corresponding branched products in excellent yield and in up to 95% ee. The developed catalytic asymmetric reaction was successfully applied to a formal enantioselective synthesis of (−)-paroxetine.     

Copper-catalyzed cross-coupling of sulfonamides with aryl iodides and bromides facilitated by amino acid ligands

A highly general, convenient, and inexpensive catalyst system was developed for the N-arylation of sulfonamides with aryl iodides or bromides by using 5-20 mol % of CuI as catalyst, 20 mol % of N-methylglycine (for aryl iodides) or N,N-dimethylglycine (for aryl bromides) as ligand, and K₃PO₄ as base.     

Kinetic resolution of 5-substituted cycloalkenones by peptidic amidophosphane-copper-catalyzed asymmetric conjugate addition of dialkylzinc

Asymmetric conjugate alkylation reaction of racemic 5-substituted cyclohexenones with dialkylzinc reagents was catalyzed by 2-5 mol % of dipeptidic amidophosphane-Cu(MeCN)₄BF₄ in toluene at 0 °C for 20 min to recover enantioenriched starting 5-substituted cyclohexenones with 88-98% ee in 28-41% yield along with trans major 3-alkylated 5-substituted cyclohexanones with 81-90% ee in 53-60% yield. Complete consumption of starting racemic 5-TMS-cyclohexenone by treating with diethylzinc under the catalytic asymmetric reaction conditions gave trans major 85:15 mixture of trans- and cis-3-ethyl-5-TMS-cyclohexanones with 15% ee (for trans) in 83% combined yield, indicating that the conformation-controlled trans-alkylation of cyclohexenone prevails over chiral catalyst-controlled enantiofacial differentiation.     

Amino acid-mediated Goldberg reactions between amides and aryl iodides

A highly general, experimentally simple, and inexpensive catalyst system was developed for the amidation of aryl iodides by using 5 mol % of CuI as catalyst, 20 mol % of an amino acid as ligand, and K₃PO₄ as base.     

Further improvements of the dibutyl tin oxide-catalyzed regioselective diol tosylation

In this Letter, we report that selective monotosylation of a 1,2-diol is possible using only 0.1 mol % of Bu₂SnO. More interestingly, we found that the corresponding tin acetal 3b gave faster conversions and more reproducible reaction times. Moreover, the loading of this catalyst could be as low as 0.05-0.005 mol %.     

Catalytic asymmetric epoxidation of α,β-unsaturated N-acylpyrroles as monodentate and activated ester equivalent acceptors

Catalytic asymmetric epoxidation of α,β-unsaturated N-acylpyrroles as monodentate and activated ester equivalent acceptors is described. A Sm(O-i-Pr)₃/(R)-H₈-BINOL complex promoted the epoxidation reaction to afford products in high yield (up to quant) and high enantiomeric excess (up to >99.5% ee). Reaction proceeded smoothly using cumene hydroperoxide (CMHP) with low explosive hazard, and completed within 0.2-0.5 h with 5 mol % catalyst. Catalyst loading was successfully reduced to as little as 0.02 mol %. The N-acylpyrrole properties as well as efficient synthesis of α,β-unsaturated N-acylpyrroles are also described.     

Highly selective glycine phase-transfer catalysis using fluoroanthracenylmethyl cinchonidine catalysts

Fluoroanthracenylmethyl cinchonidine phase-transfer catalysts have been produced and explored for asymmetric glycine alkylation. The fluoroanthracenylmethyl precursors were made from aryloxazolidinones and aldehydes using an efficient electrophilic substitution with phosphorous pentoxide. The cinchonidine catalysts promote highly selective glycine alkylation under mild conditions. The 1,8-difluoroanthracenyl-10-methyl catalyst 6 (10 mol %) in toluene/THF with 50% aqueous KOH (−20 °C) promoted benzylation of glycine 1 to give 2 in 86% yield, 98% ee. Other electrophiles also gave excellent selectivity and reactivity.     

Pd-catalyzed enantioselective synthesis of quaternary α-amino acid derivatives using a phenylalanine-derived P-chirogenic diaminophosphine oxide

A Pd-catalyzed enantioselective synthesis of quaternary α-amino acid derivatives using a phenylalanine-derived P-chirogenic diaminophosphine oxide is described. Asymmetric allylic substitution using acyclic β-keto esters with a nitrogen functional group at the α-carbon as prochiral nucleophiles proceeded in the presence of 5 mol % of Pd catalyst, 10 mol % of chiral diaminophosphine oxide 1j, BSA, and appropriate additives, affording the corresponding quaternary α-amino acid derivatives in excellent yield and in up to 92% ee.     

Catalytic cyanosilylation of ketones using organic catalyst 1,1,3,3-tetramethylguanidine

1,1,3,3-Tetramethylguanidine acts as a highly effective catalyst for cyanosilylation of various ketones and aldehydes to the corresponding cyanohydrin trimethylsilyl ethers in up to 99% yield. The reaction proceeds smoothly with 0.1 mol % catalyst loading at 25 °C under solvent-free conditions.     

Asymmetric addition of KCN and Ac2O to aldehydes catalyzed by recyclable polymeric salen-Ti(IV) complexes

Polymeric salen-Ti(IV) complexes were employed in the enantioselective O-acetyl cyanation of aldehydes with KCN and Ac₂O. The polymeric catalysts with appropriate crosslinking degree exhibited good activities and enantioselectivities, up to 94% yield and 91% ee were obtained at −20 °C with 1 mol % of catalyst (based on bimetallic catalytic unit). Moreover, the crosslinked polymeric catalyst could be easily recovered and reused for six consecutive runs without obvious decrease in activity and enantioselectivity.     

Facile preparation of optically pure diamines and their applications in asymmetric aldol reactions

A family of optically pure diamines with tertiary-primary amine motif has been synthesized from optically pure binaphthol and amino acids. The catalysts are highly tunable in structure and has demonstrated high efficiency in direct aldol reactions. Thus, a variety of aldehydes or methyl 2-oxoacetates reacted with acetone in the presence of 10 mol % of catalyst and 20 mol % TFA, furnishing the desired alcohols in up to 99% yield with excellent enantioselectivities (up to 96% ee).     

Catalytic enantioselective alkenylation and phenylation of trifluoromethyl ketones

Catalytic enantioselective alkenylation and phenylation of trifluoromethyl ketones are described. High enantioselectivity (up to 84% ee) was produced in an alkenylation of aryl trifluoromethyl ketones using a CuF-DTBM-SEGPHOS complex as the catalyst (5-10 mol %) and alkenylsilanes as the nucleophile. This is the first example of catalytic enantioselective alkenylation of trifluoromethyl ketones. The products are versatile chiral building blocks, which contain a trifluoromethyl-substituted tertiary alcohol moiety.     

Palladium-catalyzed cross-coupling of trimethoxysilylbenzene with aryl bromides and chlorides using phosphite ligands

Phosphites were employed as ligands in palladium-catalyzed Hiyama coupling reactions. The optimized reaction conditions were equimolar amounts (5 mol % each) of Pd(acac)₂ and phosphite 1 in p-xylene at 80 °C with TBAF as an additive. This catalyst system exhibited high activities in the reactions with trimethoxysilylbenzene and aryl bromides that have electron-donating or electron-withdrawing groups. In the case of aryl chlorides, substrates possessing electron-withdrawing groups gave the coupled products in high yields.