High Syn Selectivity Research Articles

Highly Stereoselective Synthesis of Functionalized β,β‐Di‐ and Trisubstituted Vinylic Sulfoxides by Cu‐Catalyzed Conjugate Addition of Organozinc Reagents.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Preparation of γ‐Siloxyallyltributylstannanes and Their Use in the Synthesis of (.+‐.)‐1‐Deoxy‐6,8a‐di‐epi‐castanospermine.

AbstractFor Abstract see ChemInform Abstract in Full Text.

1,2-syn-Selective and Enantioselective Michael Reactions of Acyclic Enones with a Propionate-Derived Nucleophile Catalyzed by Oxazaborolidinone

allo-Threonine-derived oxazaborolidinone 1b is demonstrated to be an effective catalyst for the stereoselective Michael reaction of simple acyclic enones with propionate-derived silyl ketene acetals. The reaction affords the corresponding Michael adducts with two contiguous asymmetric centers with high syn selectivity and enantioselectivity.

A Cation-Exchange Resin Promoted Imino Aldol Reaction of Chiral Alkoxyketene Silyl Acetals with α,β-Unsaturated Imines, Leading to a Facile Synthesis of β-Lactams

Imino aldol reaction of chiral ketene silyl acetals derived from 3-hydroxybutanoates with α,β-unsaturated imines proceeds smoothly to give β-amino esters in good yields with high syn-selectivity under the influence of a cation-exchange resin. Subsequent treatment with tert-butylmagnesium chloride gave β-lactams in a highly stereoselective manner.

Unusual Palladium-Catalyzed Silaboration of Allenes Using Organic Iodides as Initiators: Mechanism and Application

A highly regio- and stereoselective method for the synthesis of various 2-silylallylboronates 7 from allenes 1 and 2-(dimethylphenylsilanyl)-4,4,5,5-tetramethyl[1,3,2]dioxaborolane (5) catalyzed by palladium complexes and initiated by organic iodides is described. Treatment of monosubstituted aryl and alkylallenes RCH=C=CH(2) (1a-m) and 1,1-dimethylallene (1n) with borylsilane 5 in the presence of Pd(dba)(2) (5 mol %) and organic iodide 3a (10 mol %) afforded the corresponding silaboration products 7a-n in moderate to excellent yields. This catalytic silaboration is totally regioselective with the silyl group of 5adding to the central carbon and the boryl group to the unsubstituted terminal carbon of allene. Furthermore, the reactions show very high E stereoselectivity with the Z/E ratios lying in the range from 1/99 to 7/93. In the absence of an organic iodide, silaboration of 1 with 5 still proceeds, but gives products having completely different regiochemistry as that of 7. The silaboration chemistry can be applied to the synthesis of homoallylic alcohols. Treatment of allenes (1) with borylsilane 5 and aldehydes 14 in the presence of Pd(dba)(2) (5 mol %) and 3a (10 mol %) at 80 degrees C in ethyl acetate for 5 h afforded homoallylic alcohols 15a-p in one pot in good to excellent yields, with exceedingly high syn selectivity (>93%). Mechanistic pathways involving an unusual palladium-catalyzed three-component assembling reaction of dimethylphenylsilyl iodide, allene 1, and borylsilane 5 were proposed to account for these catalytic reactions.

Highly Stereoselective Synthesis of Functionalized β,β-Di- and Trisubstituted Vinylic Sulfoxides by Cu-Catalyzed Conjugate Addition of Organozinc Reagents

beta,beta-Disubstituted chiral vinylic sulfoxides bearing functionalities have been synthesized via Cu-catalyzed conjugate addition of organozinc reagents to chiral 1-alkynyl sulfoxides. Due to the availability of functionalized organozinc reagents and high syn-selectivity of the reaction, both geometric beta,beta-disubstituted vinylic sulfoxides were selectively synthesized. Furthermore, 1-alkynyl sulfoxides were derivatized into trisubstituted vinylic sulfoxides by trapping the resulting alpha-sulfinyl vinylic carbanion with electrophiles. Highly diastereoselective THF and THP ring formations were accomplished by means of this methodology followed by an intramolecular Michael addition.

Substituent effect on the diastereoselectivity in the chelation-controlled radical reactions of γ-( p-substituted-benzyloxy)-α-methylene esters with alkyl iodides

A pronounced substituent effect on the diastereoselectivity in the chelation controlled radical reactions of ethyl γ-( p-substituted-benzyloxy)-α-methylenecarboxylates with alkyl iodides was observed. The syn-selectivity increased in the order of electron-donating ability NO 2<CN<CF 3<F<H< i-Pr, Me, OMe of the p-substituent, and the plot of the log( syn/ anti) versus Hammett sigma constants gave a linear correlation. The complexation experiments of the substrates with Lewis acid using 1H NMR spectroscopy and the competition experiments between p-isopropylbenzyloxy and p-trifluoromethylbenzyloxy esters showed that the electron-donating p-isopropyl group stabilized the seven-membered chelate ring to give high syn-selectivity.

Geometrically Selective Synthesis of Sulfur-containing Heterocycles by Intramolecular Pd-catalyzed Sulfinylzincation

A new method to synthesize cyclic sulfoxide derivatives was developed utilizing Pd-catalyzed sulfinylzincation, which proceeds with high syn-selectivity under mild conditions. The resulting vinylzinc species reacted with electrophiles such as proton, allyl bromide, and benzoyl chloride to afford a single geometric isomer.

Preparation of γ-siloxyallyltributylstannanes and their use in the synthesis of (±)-1-deoxy-6,8a-di-epi-castanospermine

gamma-siloxyallyltributylstannanes were selectively obtained as E or Z isomers from beta-tributylstannylacrolein upon reaction with lithium or magnesium alkylcyanocuprates. The ability of the reagents to give a high syn selectivity when added to iminium salts has been used for the efficient synthesis of (+/-)-1-deoxy-6,8a-di-epi-castanospermine from succinimide. The key step of the synthesis was the allylstannation of the N-allyliminium intermediate followed by ring closing metathesis.

Geometrically Selective Synthesis of Functionalized β,β‐Disubstituted Vinylic Sulfoxides by Cu‐Catalyzed Conjugate Addition of Organozinc Reagents to 1‐Alkynyl Sulfoxides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Indium‐Mediated Allylation of Carbonyl Compounds with an Allylic Bromide in Aqueous Media: Anomalous syn‐Diastereoselectivity Regardless of Allylic Bromide Geometry.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Geometrically selective synthesis of functionalized beta,beta-disubstituted vinylic sulfoxides by Cu-catalyzed conjugate addition of organozinc reagents to 1-alkynyl sulfoxides.

[reaction: see text] A new synthetic method of chiral beta,beta-disubstituted vinylic sulfoxides bearing various functionalities has been developed by employing Cu-catalyzed conjugate addition of an organozinc reagent to chiral 1-alkynyl sulfoxide. Since the reaction proceeds with very high syn-selectivity, both geometric beta,beta-disubstituted vinylic sulfoxides were stereoselectively synthesized by changing the combination of 1-alkynyl sulfoxide and the organozinc reagent.

A New Type of Catalytic Tandem 1,4‐Addition—Aldol Reaction which Proceeds Through an (Oxa‐π‐allyl)rhodium Intermediate.

The reaction of 9-aryl-9-borabicyclo[3.3.1]nonanes (B-Ar-9BBN) with alpha,beta-unsaturated ketones and aldehydes in the presence of 3 mol % [Rh(OMe)(cod)](2) in toluene at 20 degrees C for 2 h gave high yields of the tandem 1,4-addition-aldol reaction products with high syn selectivity. The reaction proceeds through the catalytic cycle consisting of 1,4-addition of an organorhodium species to an alpha,beta-unsaturated ketone and the aldol addition of the resulting (oxa-pi-allyl)rhodium intermediate to an aldehyde.

Indium-mediated allylation of carbonyl compounds with an allylic bromide in aqueous media: anomalous syn-diastereoselectivity regardless of allylic bromide geometry

Anomalous syn-diastereoselectivity of indium-mediated coupling of aldehydes with bromides Z- 3b and E- 3b is reported. The reaction afforded high syn selectivity regardless of the allylic bromide geometry. Preliminary studies on the enantioselective indium-mediated allylation were attempted and found to give the desired products in moderate yield with high syn selectivity and enantioselectivity.

Diastereoselectivity in the reduction of alpha-Oxy- and alpha-amino-substituted acyclic ketones by polymethylhydrosiloxane.

Diastereoselectivity in the reduction of alpha-alkoxy-, alpha-acyloxy-, and alpha-alkylamino-substituted ketones with polymethylhydrosiloxane (PMHS) in the presence of fluoride ion catalysis was investigated. High syn-selectivity was observed in the reduction of alpha-alkoxy, alpha-acyloxy, and alpha-dialkylamino ketones. Reduction of alpha-monoalkylamino ketone proceeded in anti-selective manner with moderate selectivity. The observed selectivity is explained based on Felkin-Anh and Cram-chelate models.

Theoretical Studies on the Diastereoselectivity in the Lewis Acid Catalyzed CarbonylEne Reaction: A Fundamental Role of Electrostatic Interaction

AbstractLewis acids affect reactivity, selectivity, and mechanism in the carbonyl‐ene reaction. The diastereoselectivity in the glyoxylate‐ene reaction depends on Lewis acids. While the SnCl4‐promoted reaction can be achieved with a high level of anti‐selectivity, the use of Al reagents leads to a high syn‐selectivity. The origin of the Lewis acid dependency of the diastereoselectivity in the carbonylene reaction of (E)‐but‐2‐ene with glyoxylate was theoretically studied (HF/6‐31G*) from the point of view of differences and similarities between the ene and the Diels–Alder reactions. Though it has been widely accepted that the endo‐preference would be less obvious in the ene reaction than in the Diels–Alder reaction, our ab initio molecular studies showed that the electrostatic interaction between carbonyl O‐atom lone pair and cationic allylic central C‐atom of ene component exists in the Lewis acid‐promoted carbonyl–ene reaction to affect the transition‐state conformation. It is illustrated that such an electrostatic interaction is essential to control the exo/endo‐selectivity, which provides the diastereoselectivity of the product in the transition state of the Lewis acid promoted carbonylene reaction.

A new type of catalytic tandem 1,4-addition-aldol reaction which proceeds through an (oxa-pi-allyl)rhodium intermediate.

The reaction of 9-aryl-9-borabicyclo[3.3.1]nonanes (B-Ar-9BBN) with alpha,beta-unsaturated ketones and aldehydes in the presence of 3 mol % [Rh(OMe)(cod)](2) in toluene at 20 degrees C for 2 h gave high yields of the tandem 1,4-addition-aldol reaction products with high syn selectivity. The reaction proceeds through the catalytic cycle consisting of 1,4-addition of an organorhodium species to an alpha,beta-unsaturated ketone and the aldol addition of the resulting (oxa-pi-allyl)rhodium intermediate to an aldehyde.

On the diastereocontrol in the formation of (2 R,3 S)-3-(3′-furyl)-1,2- O-isopropylidenedioxy-3-pentanol and its (2 R,3 R)-diastereomer

The two enantiomeric bicyclic lactone skeletons of the marine natural products plakortones, whose absolute configuration are yet unknown, are approachable from (2 R,3 S)-3-(3′-furyl)-1,2- O-isopropylidenedioxy-3-pentanol 1a and its (2 R,3 R)-diastereomer 1b . To obtain these optically pure diastereomers, two pathways were studied, in which different solvents, additives and nucleophilic reagents were employed. The stereochemistry was successfully controlled in the reaction of (2 R)-1,2- O-isopropylidenedioxy-3-pentanone 3 with 3-furyllithium, which gave high syn-selectivity in Et 2O, but excellent anti-selectivity in toluene.

A Highly syn-Selective Allylation of Aldehydes in Water

nBu4NBr/PbI2 acts as an effective catalyst for the allylation of aldehydes 2 with the allylic tin reagents 1 in water. A high syn-selectivity of 3 was achieved in water without any aprotic solvents in the reaction of the aromatic aldehydes 2 with the crotyltri-n-butyltin reagents 1b, 1c irrespective of their E/Z geometry.

Stereoselective aldol reaction of α-seleno carbonyl compounds: preparation of ( Z)-α,β-unsaturated carbonyl compounds

The aldol reaction of the titanium enolates of α-seleno esters in the presence of Ph 3P or Ph 3PO gave the products with high stereoselectivity favoring the syn isomers. Reaction of α-seleno ketones with TiCl 4 in the presence of 2 equiv. of Et 3N, and subsequently with aldehydes, gave the aldol products with high syn selectivity. The stereoselectivity in the aldol reaction of 3-pentanone also increased by using an excess amount of Et 3N. The aldol products thus obtained from the α-seleno carbonyl compounds could be stereospecifically converted to ( Z)-α,β-unsaturated carbonyl compounds by treatment with pyridine. ( Z)-Alkylidenecyclopentanones were exclusively formed by treatment of the syn-aldol products with Et 3N in the dark.