A Lewis Acid-Controlled Enantiodivergent Epoxidation of Aldehydes.

Two epoxidation catalysts, one of which consists of two VANOL ligands and an aluminum and the other that consists of two VANOL ligands and a boron, were compared. Both catalysts are highly effective in the catalytic asymmetric epoxidation of a variety of aromatic and aliphatic aldehydes with diazoacetamides, giving high yields and excellent asymmetric inductions. The aluminum catalyst is effective at 0 °C and the boron catalyst at -40 °C.

Employing a chiroptical sensor for the absolute stereochemical determination of α-amino and α-hydroxyphosphonates.

The absolute stereochemistry of the α-amino and α-hydroxyphosphonates is determined using a chiroptical sensor. The induced helicity of the host-guest complex is correlated to the chirality of the guest molecule a simple binding model. The relative size of the substituents dictates the predominant helical population, leading to an easy circular dichroic readout.

Probing Catalyst Function - Electronic Modulation of Chiral Polyborate Anionic Catalysts.

Boroxinate complexes of VAPOL and VANOL are a chiral anionic platform that can serve as a versatile staging arena for asymmetric catalysis. The structural underpinning of the platform is a chiral polyborate core that covalently links together alcohols (or phenols) and vaulted biaryl ligands. The polyborate platform is assembled in situ by the substrate of the reaction, and thus a multiplex of chiral catalysts can be rapidly assembled from various alcohols (or phenols) and bis-phenol ligands for screening of catalyst activity.

Zirconium-catalyzed asymmetric Kabachnik-Fields reactions of aromatic and aliphatic aldehydes.

An effective catalyst has been developed for the three-component reaction of aldehydes, anilines and phosphites in an asymmetric catalytic Kabachnik-Fields reaction to give α-aminophosphonates. A catalyst was sought that would give high asymmetric inductions for aromatic and, and more particularly, for aliphatic aldehydes since there has not previously been an effective catalyst developed for this class of aldehydes. The optimal catalyst is prepared from three equivalents of the 7,7'-di--butylVANOL ligand, one equivalent of -methylimidazole and one equivalent of zirconium tetraisopropoxide.

Resolution of Vaulted Biaryl Ligands via Borate Esters of Quinine and Quinidine.

Given the sudden and unexplained rise in the cost of (+)- and (-)-sparteine, an alternative method for the resolution of vaulted biaryls has been developed. This method involves the reaction of a racemic vaulted biaryl ligand with one equivalent of BH·SMe and one equivalent of either quinine or quinidine. A precipitate then forms from the resulting mixture of diastereomeric borates as a result of differential solubilities.

Catalytic Asymmetric Epoxidation of Aldehydes with Two VANOL-Derived Chiral Borate Catalysts.

A highly diastereo- and enantioselective method for the epoxidation of aldehydes with α-diazoacetamides has been developed with two different borate ester catalysts of VANOL. Both catalytic systems are general for aromatic, aliphatic, and acetylenic aldehydes, giving high yields and inductions for nearly all cases. One borate ester catalyst has two molecules of VANOL and the other only one VANOL.

Multicomponent Catalytic Asymmetric Synthesis of trans-Aziridines.

A multicomponent trans-aziridination of aldehydes, amines, and diazo compounds with BOROX catalysts is developed. The optimal protocol is slightly different for aryl aldehydes than for aliphatic aldehydes. The key to the success with aryl aldehydes was allowing the catalyst, aldehyde, and amine to react for 20 min before addition of the diazo compound.

Pyro-Borates, Spiro-Borates, and Boroxinates of BINOL-Assembly, Structures, and Reactivity.

VANOL and VAPOL ligands are known to react with three equivalents of B(OPh) to form a catalytic species that contains a boroxinate core with three boron atoms, and these have proven to be effective catalysts for a number of reactions. However, it was not known whether the closely related BINOL ligand will likewise form a boroxinate species. It had simply been observed that mixtures of BINOL and B(OPh) were very poor catalysts compared to the same mixtures with VANOL or VAPOL.

Multicomponent cis- and trans-Aziridinatons in the Syntheses of All Four Stereoisomers of Sphinganine.

All four stereoisomers of sphinganine can be synthesized by a multicomponent aziridination of an aldehyde, an amine and an α-diazo carbonyl compound mediated by a BOROX catalyst with high asymmetric induction (≥96% ee). The threo isomers are available from ring-opening of cis-aziridines by an oxygen nucleophile with inversion at the C-3 position and the erythro-isomers are likewise available from trans-aziridines.

Enantioselective Palladium-Catalyzed Carbonylative Carbocyclization of Enallenes via Cross-Dehydrogenative Coupling with Terminal Alkynes: Efficient Construction of α-Chirality of Ketones.

An enantioselective Pd /Brønsted acid-catalyzed carbonylative carbocyclization of enallenes ending with a cross-dehydrogenative coupling (CDC) with a terminal alkyne was developed. VAPOL phosphoric acid was found as the best co-catalyst among the examined 28 chiral acids, for inducing the enantioselectivity of α-chiral ketones. As a result, a number of chiral cyclopentenones were easily synthesized in good to excellent enantiomeric ratio with good yields.

Catalyst-Controlled Multicomponent Aziridination of Chiral Aldehydes.

A highly diastereoselective and enantioselective method for the multicomponent aziridination of chiral aldehydes has been developed with BOROX catalysts of the VANOL (3,3'-diphenyl-2,2'-bi-1-naphthol) and VAPOL (2,2'-diphenyl-(4-biphenanthrol)) ligands. Very high to perfect catalyst control is observed with most all substrates examined including aldehydes with chiral centers in the α- and β-positions. High catalyst control was also observed for a number of chiral heterocyclic aldehydes allowing for the preparation of epoxy aziridines, bis(aziridines) and ethylene diaziridines.

Self-Assembly of a Library of Polyborate Chiral Anions for Asymmetric Catalytic Quinoline Reduction.

The 'template' polyborate BOROX catalysts are shown to mediate the asymmetric transfer hydrogenation of 2-quinolines. The rapid and simple generation of a large family of BOROX catalysts with significantly altered asymmetric pockets is described. A transition state model that explains the enantioselectivity is proposed.

β-amino esters from the reductive ring opening of aziridine-2-carboxylates.

A general study is undertaken to examine the scope of the reductive ring opening of aziridine-2-carboxylates with samarium diiodide. The competition between C-C and C-N bond cleavage is examined as a function of the nature of the N-substituent of the aziridine, the nature of the substituent in the 3-position of the aziridine, and whether the substituent in the 3-position is in a cis or trans relationship with the carboxylate in the 2-position. The desired C-N bond cleavage leads to β-amino esters that are the predominant products for most aziridines with an N-activating group.

Catalytic asymmetric α-Iminol rearrangement: new chiral platforms.

A series of 19 different asymmetric catalysts were screened in an effort to identify the first chiral catalyst for the rearrangement of α-hydroxy imines to α-amino ketones involving a 1,2-carbon shift. Although aluminate complexes of VAPOL, VANOL, and 7,7'-(t)Bu2VANOL were quite effective catalysts giving up to 88% ee, the ne plus ultra catalyst for this reaction was found to be a zirconium complex of VANOL which gives 97 to >99% ee for the majority of the substrates examined. An X-ray diffraction study of the catalyst reveals that the zirconium exists as a homoleptic complex with three VANOL ligands and two protonated N-methyl imidazoles.

Enantioselective biomimetic total syntheses of kuwanons I and J and brosimones A and B.

The first enantioselective total syntheses of prenylflavonoid Diels-Alder natural products (-)-kuwanon I, (+)-kuwanon J, (-)-brosimone A, and (-)-brosimone B have been accomplished from a common intermediate based on a concise synthetic strategy. Key elements of the synthesis include a biosynthesis-inspired asymmetric Diels-Alder cycloaddition mediated by a chiral ligand/boron Lewis acid, as well as a process involving regioselective Schenck ene reaction, reduction, and dehydration to realize a biomimetic dehydrogenation for generation of the required diene precursor. Furthermore, a remarkable tandem inter-/intramolecular asymmetric Diels-Alder cycloaddition process was applied for the synthesis of (-)-brosimone A.

Transition state analysis of enantioselective Brønsted base catalysis by chiral cyclopropenimines.

Experimental (13)C kinetic isotope effects have been used to interrogate the rate-limiting step of the Michael addition of glycinate imines to benzyl acrylate catalyzed by a chiral 2,3-bis(dicyclohexylamino) cyclopropenimine catalyst. The reaction is found to proceed via rate-limiting carbon-carbon bond formation. The origins of enantioselectivity and a key noncovalent CH···O interaction responsible for transition state organization are identified on the basis of density functional theory calculations and probed using experimental labeling studies.

Three-component asymmetric catalytic Ugi reaction--concinnity from diversity by substrate-mediated catalyst assembly.

The first chiral catalyst for the three-component Ugi reaction was identified as a result of a screen of a large set of different BOROX catalysts. The BOROX catalysts were assembled in situ from a chiral biaryl ligand, an amine, water, BH3·SMe2, and an alcohol or phenol. The catalyst screen included 13 different ligands, 12 amines, and 47 alcohols or phenols.

Vaulted biaryls in catalysis: A structure-activity relationship guided tour of the immanent domain of the VANOL ligand.

The active site in the BOROX catalyst is a chiral polyborate anion (boroxinate) that is assembled in situ from three equivalents of B(OPh)3 and one of the VANOL ligand by a molecule of substrate. The substrates are bound to the boroxinate by H bonds to oxygen atoms O1-O3. The effects of introducing substituents at each position of the naphthalene core of the VANOL ligand are systematically investigated in an aziridination reaction.

Isotope effects and mechanism of the asymmetric BOROX Brønsted acid catalyzed aziridination reaction.

The mechanism of the chiral VANOL-BOROX Brønsted acid catalyzed aziridination reaction of imines and ethyldiazoacetate has been studied using a combination of experimental kinetic isotope effects and theoretical calculations. A stepwise mechanism where reversible formation of a diazonium ion intermediate precedes rate-limiting ring closure to form the cis-aziridine is implicated. A revised model for the origin of enantio- and diastereoselectivity is proposed based on relative energies of the ring-closing transition structures.

Synthesis of [m.n]cyclophanes: regiochemistry transfer from vinyl halides to cyclophanes via Fischer carbene complexes.

The double benzannulation of bis-carbene complexes of chromium with α,ω-diynes generates [m.n]cyclophanes in which all three rings are generated in a single reaction. This triple annulation process is very flexible allowing for the construction of symmetrical [n.

Total synthesis of sedum alkaloids via catalyst controlled aza-Cope rearrangement and hydroformylation with formaldehyde.

The catalytic asymmetric aminoallylation of chiral aldehydes is developed as a new method for the catalyst controlled synthesis of syn- and anti-1,3-aminoalcohols. This methodology is highlighted in the synthesis of the sedum alkaloids (+)-sedridine and (+)-allosedridine both of which have their final carbon incorporated during closure of the piperidine ring via a hydroformylation with formaldehyde.

BOROX catalysis: self-assembled amino-BOROX and imino-BOROX chiral Brønsted acids in a five component catalyst assembly/catalytic asymmetric aziridination.

A five-component catalyst assembly/aziridination reaction is described starting from an aldehyde, an amine, ethyl diazoacetate, B(OPh)(3), and a molecule of a vaulted biaryl ligand (VAPOL or VANOL). A remarkable level of chemo-selectivity was observed since, while 10 different products could have resulted from various reactions between the five components, an aziridine was formed in 85% yield and 98% ee and only two other products could be detected in 3% yield. Studies reveal that the first in a sequence of three reactions is an exceedingly rapid amine-induced assembly of an amino-BOROX chiral Brønsted acid species from VAPOL and B(OPh)(3), which is followed by imine formation from the amine and aldehyde and the concomitant formation of an imino-BOROX chiral Brønsted acid and finally the reaction of the imine with ethyl diazoacetate mediated by the imino-BOROX catalyst to give aziridine-2-carboxylic esters with very high diastereo- and enantioselectivity.

Double stereodifferentiation in the catalytic asymmetric aziridination of imines prepared from α-chiral amines.

The catalytic asymmetric aziridination of imines and diazo compounds (AZ reaction) mediated by boroxinate catalysts derived from the VANOL and VAPOL ligands was investigated with chiral imines derived from five different chiral, disubstituted, methyl amines. The strongest matched and mismatched reactions with the two enantiomers of the catalyst were noted with disubstituted methyl amines that had one aromatic and one aliphatic substituent. The synthetic scope for the AZ reaction was examined in detail for α-methylbenzyl amine for cis-aziridines from α-diazo esters and for trans-aziridines from α-diazo acetamides.