Bismuth Triflate‐Catalyzed Addition of Allylsilanes to N‐Alkoxycarbonylamino Sulfones: Convenient Access to 3‐Cbz‐Protected Cyclohexenylamines

Bismuth triflate was found to be an efficient catalyst in the Sakurai reaction of allyltrimethylsilanes with N‐alkoxycarbonylamino sulfones. The reaction proceeded smoothly with a low catalyst loading of Bi(OTf)₃⋅4 H₂O (2–5 mol%) to afford the corresponding protected homoallylic amines in very good yields (up to 96%). A sequential allylation reaction followed by ring‐closing metathesis delivers 6–8 membered 3‐Cbz‐protected cycloalkenylamines.     

A Novel Enantioselective Catalytic Tandem Oxa‐Michael–Henry Reaction: One‐Pot Organocatalytic Asymmetric Synthesis of 3‐Nitro‐2H‐chromenes

An enantioselective oxa‐Michael–Henry reaction of substituted salicylaldehydes with nitroolefins that proceeds though an aromatic iminium activation (AIA) has been developed by using a chiral secondary amine organocatalyst and salicylic acid as a co‐catalyst. The corresponding 3‐nitro‐2H‐chromenes were obtained in moderate‐to‐good yields with up to 91% ee under mild conditions. Based on the experimental results and ESI‐mass spectrometric detection of the intermediates, a plausible transition state has been proposed to explain the origin of the activation and the asymmetric induction.     

Enantioselective Phase‐Transfer Catalytic α‐Benzylation and α‐Allylation of α‐tert‐Butoxycarbonyllactones

A new enantioselective α‐benzylation and α‐allylation of α‐tert‐butoxycarbonyllactones was devloped. α‐Benzylation and α‐allylation of α‐tert‐butoxycarbonylbutyrolactone and α‐tert‐butoxycarbonylvalerolactone under phase‐transfer catalytic conditions (50% cesium hydroxide, toluene, −60 °C) in the presence of (S,S)‐3,4,5‐trifluorophenyl‐NAS bromide (1 mol%) afforded the corresponding α‐substituted α‐tert‐butoxycarbonyllactones in very high chemical yields (up to 99%) and optical yields (up to 99% ee). The synthetic potential of this method has been successfully demonstrated by the asymmetric synthesis of unnatural α‐quaternary homoserines, 3‐alkyl‐3‐carboxypyrrolidine and 3‐alkyl‐3‐carboxypiperidine.     

Enantioselective Additions of Aryltitanium Tris(isopropoxide) to Ketones: Structure of [(i‐PrO)2Ti{μ‐(S)‐BINOLate}(μ‐O‐i‐Pr)TiPh(O‐i‐Pr)2], Study of Mechanistic and Stereochemical Insights

Aryl addition reactions of ArTi(O‐i‐Pr)₃ to aromatic, heteroaromatic, or α,β‐unsaturated ketones are described, producing tertiary alcohols in good to excellent enantioselectivities of up to 97% ee. The structure of the dititanium complex [(i‐PrO)₂Ti{μ‐(S)‐BINOLate}(μ‐O‐i‐Pr)TiPh(O‐i‐Pr)₂] [(S)‐ 4 ] that simultaneously bears a chiral directing ligand and a nucleophile is reported. Complex (S)‐ 4 possesses a pocket structure and has been illustrated as the key active species for addition reactions of both aldehydes and ketones. Mechanistic and stereochemical insights concerning addition reactions of organometallic reagents to organic carbonyls are rationalized based on the pocket structure and pocket size of (S)‐ 4 .     

Asymmetric Friedel–Crafts Alkylations of Indoles with Ethyl Glyoxylate Catalyzed by (S)‐BINOL‐Titanium(IV) Complex: Direct Access to Enantiomerically Enriched 3‐Indolyl(hydroxy)acetates

Enantioselective Friedel–Crafts alkylation reactions of a variety of indoles with ethyl glyoxylate, catalyzed by a chiral (S)‐BINOL‐Ti(IV) complex (10 mol %), are reported. The corresponding ethyl 3‐indolyl(hydroxy)acetates were formed in good yields and with high enantiomeric excess (up to 96 %). When methyl pyruvate or p‐chlorophenylglyoxal was used, the bisindole compound was obtained in excellent yield. A possible mechanism is proposed.     

Enantioselective Aza‐Henry Reaction of Imines Bearing a Benzothiazole Moiety Catalyzed by a Cinchona‐Based Squaramide

An efficient enantioselective aza‐Henry reaction of nitroalkanes to imines bearing a benzothiazole moiety catalyzed by a Cinchona‐based squaramide has been developed. In the reaction of imines, the corresponding products were obtained in good to excellent yields (up to 99%) with excellent enantioselectivities (up to >99% ee) for most of the aromatic substituted imines. The imines with electron‐withdrawing groups gave better yields than those bearing electron‐donating groups in the aza‐Henry reaction. Moreover, a one‐pot three‐component enantioselective aza‐Henry reaction using 2‐aminobenzothiazoles, aldehydes, and nitromethane was also developed. Moderate to good yields and high enantioselectivities were obtained in the one‐pot cases (up to 98% ee).     

Bis(3,5‐dimethylphenyl)‐(S)‐pyrrolidin‐2‐ylmethanol: an Improved Organocatalyst for the Asymmetric Epoxidation of α,β‐Enones

The asymmetric epoxidation of α,β‐enones by the readily available bis(3,5‐dimethylphenyl)‐(S)‐pyrrolidin‐2‐ylmethanol and tert‐butyl hydroperoxide (TBHP) is described. Stereoelectronic substitution on the aryl moiety of diaryl‐2‐pyrrolidinemethanols was found to significantly affect the efficiency with respect to the previously reported (S)‐diphenyl‐2‐pyrrolidinemethanol. Improved reactivity and enantioselectivity were achieved with bis(3,5‐dimethylphenyl)‐(S)‐pyrrolidin‐2‐ylmethanol at reduced catalyst loading (20 mol %) with ees up to 94% for chalcone epoxides under mild reaction conditions, whereas (S)‐diphenyl‐2‐pyrrolidinemethanol afforded a maximum ee of 80%. Interestingly, the methodology is applicable to the epoxidation of more challenging aliphatic or enolizable enones with good control of the asymmetric induction (up to 87% ee).     

Organocatalytic Asymmetric Michael Addition/Carbon‐Carbon Bond Cleavage of Trifluoromethyl α‐Fluorinated gem‐Diols to Nitroolefins

A new organocatalytic asymmetric Michael addition reaction by cleavage of carbon‐carbon bonds through a mild release of trifluoroacetate has been developed. The reported method generates the decarboxylated γ‐nitro‐α‐fluorocarbonyl products with excellent enantioselectivies (up to 98% ee) and good diastereoselectivies (up to 20:1 dr).     

Direct Organocatalytic Asymmetric Mannich Addition of 3‐Substituted‐2H‐1,4‐Benzoxazines: Access to Tetrasubstituted Carbon Stereocenters

3‐Substituted‐2H‐1,4‐benzoxazines undergo a highly enantioselective direct Mannich reaction with acetone in the presence of an L ‐proline catalyst at room temperature. The corresponding N‐heterocycles with α‐tetrasubstituted carbon stereocenters were obtained in good yields (48–92%) and excellent enantioselectivity (up to >99% ee). Furthermore, a novel modification involving the diastereoselective reduction of the Mannich adduct was carried out leading to the formation of a 1,3‐amino alcohol with a chiral tetrasubstituted carbon stereocenter in high yield.

     

Step‐growth polymerization of 5‐[(9,10‐dihydro‐9,10‐ethanoanthracene‐11,12‐dicarboximido)‐3‐methylbutanoyl‐amino]isophthalic acid with aromatic diols

cis‐9,10‐dihydro‐9,10‐ethanoanthracene‐11,12‐dicarboxylic acid anhydride ( 1 ) was converted to imide acid ( 2 ) by reaction with S‐valine. Compound 2 was converted to the acid chloride ( 3 ) by reaction with thionyl chloride and then treated with 5‐aminoisophthalic acid in dry N,N‐dimethylacetamide to obtain 5‐[(9,10‐dihydro‐9,10‐ethanoanthracene‐11,12‐dicarboximido)‐3‐methylbutanoylamino]isophthalic acid ( 4 ). Direct step‐growth polymerization of this novel chiral diacid monomer 4 with a series of different diols in a system of tosyl chloride, pyridine, and N,N‐dimethylformamide was carried out. The optically active polyesters (PEs) were obtained with good yield and moderate inherent viscosity ranging from 0.23 to 0.48 dL/g. The resulting polymers were characterized with FTIR, ¹H‐NMR, and elemental analysis techniques. The prepared PEs showed good thermal stability up to 320°C as measured by thermogravimetric analysis. Specific rotation experiments demonstrated the induction of optical activity due to successful insertion of S‐valine in the structure of pendant groups. © 2010 Wiley Periodicals, Inc. J Appl Polym Sci, 2010     

MOP‐Type Binaphthyl Phosphite and Diamidophosphite Ligands and Their Application in Catalytic Asymmetric Transformations

Monodentate phosphite and diamidophosphite ligands have been developed based on O‐methyl‐BINOL. These chiral ligands are easy to prepare from readily accessible phosphorylating reagents – (S_a or R_a)‐2‐chlorodinaphtho[2,1‐d:1′,2′‐f][1,3,2]dioxaphosphepine and (2R,5S)‐2‐chloro‐3‐phenyl‐1,3‐diaza‐2‐phosphabicyclo[3.3.0]octane. The new ligands have demonstrated excellent enantioselectivity in the palladium‐catalysed allylic substitution reactions of (E)‐1,3‐diphenylallyl acetate with sodium p‐toluenesulfinate (up to 99 % ee), pyrrolidine (up to 97 % ee), dipropylamine (up to 95 % ee) and dimethyl malonate (up to 99 % ee). In the palladium‐catalysed deracemization of ethyl (E)‐1,3‐diphenylallyl carbonate, up to 96 % enantioselectivity has been achieved. The diamidophosphite ligands have exhibited very good enantioselectivity in the Rh‐catalysed asymmetric hydrogenation of dimethyl itaconate (up to 90 % ee).     

Chiral N,N′‐Dioxide–Scandium(III)‐Catalyzed Asymmetric Epoxidation of 2‐Arylidene‐1,3‐diketones with Hydrogen Peroxide

The catalytic asymmetric epoxidation of 2‐arylidene‐1,3‐diketones using aqueous 30% H₂O₂ as oxidant has been successfully realized by a N,N′‐dioxide–scandium(III) triflate [Sc(OTf)₃] complex, giving the corresponding products in moderate to good yields (up to 85%) with excellent enantioselectivities (up to 99% ee) under mild reaction conditions without extra additives.

     

C3‐Symmetric Cinchonine‐Squaramide‐Catalyzed Asymmetric Chlorolactonization of Styrene‐Type Carboxylic Acids with 1,3‐Dichloro‐5,5‐dimethylhydantoin: An Efficient Method to Chiral Isochroman‐1‐ones

A more practical and efficient catalytic asymmetric chlorolactonization of styrene‐type carboxylic acids with 1,3‐dichloro‐5,5‐dimethylhydantoin (DCDMH) using C₃‐symmetric cinchonine‐squaramide (CSCS) as organocatalyst has been developed. A series of chiral chloro‐substituted isochroman‐1‐ones was obtained in excellent yields (up to 95%) and enantioselectivities (up to 99% ee), whwereby the results for chloro‐substituted isochroman‐1‐ones are the best ever achieved. The catalyst can be recovered and reused for six cycles. Moreover, the chlorolactonization product 3b was further transformed to optically active bicyclic isochroman‐1‐one derivatives in high yield without losing the enantioselectivity. Furthermore, compounds 3e and 2n proved to be highly potent inhibitors of the HIV‐1 in TZM‐bl cells.

     

The Use of an Unusual Rearrangement Sequence for the Syntheses of 3‐(1‐Aminoalkylidene)‐3H‐thiophen‐2‐ones and two Examples of their Surprising Electrophilic‐Induced Dimerization Reactions

The reaction of 2‐amino‐3‐carbomethoxythiophene ( 1a ) and 2‐amino‐3‐carboethoxy‐4,5‐dimethylthiophene ( 1b ) with methyl‐ or ethylmagnesium chloride leads to new 3‐(1‐aminoalkylidene)‐3H‐thiophen‐2‐ones 4a—d in good yields (60—87%). Treatment of the compounds 4a and 4c with catalytic amounts of p‐TsOH in boiling CHCl₃ afforded the (±)‐4,4′‐bis‐(1‐aminoalkylidene)‐3′,4′‐4H,2′H‐[2,3′]bithiophenyl‐5,5′‐diones 9a and 9b as new interesting heterocycles in preparatively useful yields (60/mdash;65%).     

Palladium‐Catalyzed Asymmetric 1,4‐Addition of Diarylphosphines to Nitroalkenes for the Synthesis of Chiral P,N‐Compounds

A highly stereoselective asymmetric 1,4‐addition of diarylphosphines to nitroalkenes catalyzed by a bis(phosphine) pincer‐palladium complex has been developed for the synthesis of chiral P,N compounds with good to excellent enantioselectivities (up to 94% ee) under mild conditions.     

Ruthenium‐Catalyzed Asymmetric Hydrogenation of β‐Keto‐ enamines: An Efficient Approach to Chiral γ‐Amino Alcohols

A highly efficient and enantioselective hydrogenation of unprotected β‐ketoenamines catalyzed with ruthenium(II) dichloro{(S)‐(−)‐2,2′‐bis[di(3,5‐xylyl)phosphino]‐1,1′‐binaphthyl}[(2S)‐(+)‐1,1‐bis(4‐methoxyphenyl)‐3‐methyl‐1,2‐butanediamine] {Ru[(S)‐xylbinap][(S)‐daipen]Cl₂} has been successfully developed. This methodology provides a straightforward access to free γ‐secondary amino alcohols, which are key building blocks for a variety of pharmaceuticals and natural products, with high yields (>99%) and excellent enantioselectivities (up to 99% ee) in all cases.     

N‐Heterocyclic Carbene‐Mediated Enantioselective Addition of Phenols to Unsymmetrical Alkylarylketenes

Chiral N‐heterocyclic carbenes (NHCs) mediate the enantioselective addition of 2‐phenylphenol to unsymmetrical alkylarylketenes, delivering α‐alkyl‐α‐arylacetic acid derivatives with good levels of enantiocontrol (up to 84% ee). Enantiodivergent stereochemical outcomes are observed using 2‐phenylphenol and benzhydrol in the NHC‐promoted esterification reaction using a triazolium precatalyst derived from pyroglutamic acid, consistent with distinct mechanistic pathways operating within these processes.     

Organocatalytic Asymmetric Sulfa‐Michael Addition to α,β‐Unsaturated Ketones

The highly enantioselective organocatalytic sulfa‐Michael addition to α,β‐unsaturated ketones has been accomplished using benzyl and tert‐butyl mercaptans as the sulfur‐centered nucleophiles. Optically active products are obtained in high yields and good to excellent stereocontrol (up to 96 % ee) from a large variety of enones. Central to these studies has been the use of the catalytic primary amine salt A , derived from 9‐amino‐(9‐deoxy)‐epi‐hydroquinine and D ‐N‐Boc‐phenylglycine, in which both the cation and the anion are chiral, that exhibits high reactivity and selectivity for iminium ion catalysis with enones.     

Asymmetric Synthesis of 2‐Substituted Dihydrobenzofurans and 3‐Hydroxydihydrobenzopyrans through the Enantioselective Epoxidation of O‐Silyl‐Protected ortho‐Allylphenols

The Shi‐type epoxidation of O‐tert‐butyldiphenylsilyl (TBDPS) protected o‐allylphenols serves as an efficient strategy to construct the dihydrobenzofurans and dihydrobenzopyrans in up to 97% ee. This methodology led to the enantioselective synthesis of (+)‐marmesin, (−)‐(3′R)‐decursinol, and (+)‐lomatin.     

Functionalized cellulose‐supported triphenylphosphine and its application in Suzuki cross‐coupling reactions

A new heterogeneous cellulose tagged triphenylphosphine (Cell‐OPPh₃) was synthesized and subsequently coordinated with Pd(OAc)₂ to form a cellulose‐supported triphenylphosphine palladium complex (Cell‐OPPh₃‐Pd). Cell‐OPPh₃ and the corresponding palladium complex were fully characterized by TGA, SEM, TEM, and NMR analysis. Results of catalytic activity experiments indicate that the Cell‐OPPh₃‐Pd complex can efficiently catalyze Suzuki–Miyaura cross‐coupling reactions of aryl halides with arylboronic acids at mild reaction conditions. The coupling products can be obtained in good to excellent yields (up to 98%). The work‐up procedure is simple and the catalyst could be easily recovered by filtration, and then reused in next run. © 2014 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 41427.