Bryant E. Rossiter

Enantioselective conjugate addition to cyclic enones with scalemic lithium organo(amido)cuprates, Part IV. Relationship between ligand structure and enantioselectivity☆☆☆

Abstract Scalemic lithium amides derived from primary and secondary amines react with organocopper compounds in ether or dimethyl sulfide to form lithium organo(amido)cuprates capable of enantioselective conjugate addition to 2-cycloalkenones. The most successful heterocuprate, in which the chiral ligand is (S)-N-methyl-1-phenyl-2-(1-piperidinyl)ethanamine, (S)-MAPP, 13, reacts with cyclic enones to form products with up to 97% ee. Nonlinear asymmetric induction was observed with the cuprate formed from ligand 13.

Enantioselective conjugate addition with chiral amidocuprates

Abstract A series of chiral secondary amines have been screened as non-transferrable cuprate ligands for the promotion of enantioselectivity in conjugate addition to 2-cyclohexenone. A mechanism is presented to rationalize the enantioselectivity observed.

Enantioselective conjugate addition to cyclic enones with (S)-mapp-cuprates

Abstract Chiral amidocuprates, formed from CuI, n-butyl or methyl lithium and ( S )- N -methyl-1-phenyl-2-(1-piperidinyl)ethanamine, ( S )-MAPP, react enantioselectively with 5, 6, 7 and 8-membered cyclic enones to give products with up to 97% e.e. The synthesis of ( S )-MAPP is also reported.

Enantioselective conjugate addition, part V. Synthesis and testing of scalemic tetraamines as chiral cuprate ligands.

Abstract Reported herein is the enantioselective conjugate addition of n-butyl to 2-cyclopentenone, 2-cyclohexenone, 2-cycloheptenone and 2-cyclooctenone using scalemic amidocuprates derived from copper(I) iodide, n-butyllithium and a homologous series of 5 scalemic tetraamines referred to as DIMMAP-2 through -6. Cuprates derived from DIMAPP-4 manifest the highest enantioselectivities (up to 78%) and the same sense of enantioselectivity as the MAPP cuprates upon which these new cuprates are based. A previously developed mechanistic proposal has been revised to account for the observations made.

Novel cyclodextrin-oligosiloxane copolymers and their use as stationary phases for separating enantiomers in open tubular column supercritical fluid chromatography

Abstract New stationary phases composed of cyclodextrin-oligosiloxane copolymers for open tubular column supercritical fluid chromatography have been developed. These phases allow the separation of enantiomers of a variety of chiral organic solutes.

Synthesis of (1R-trans)-N,N′-1,2-cyclohexylenebisbenzamideoligodimethylsiloxane copolymers for use s chiral stationary phases for capillary supercritical fluid chromatography

Abstract Eight new copolymers have been prepared as chiral stationary phases for capillary supercritial fluid chromatography (SFC) by the copolymerization hydrosilylation of α,θ-dihydromethyloligosiloxanes with four dialkene derivatives of (1R-trans)-N,N′-1,2-cyclohexylebenbisbenzamide. This represents a novel approach to the synthesis of chiral stationary phases in that copolymers are formed from achiral α,ω-dihydrosiloxane and chiral diolefinic diamide monomers. The siloxane units ensure good general chromatographic performance (e.g., high efficiency and thermal stability), while the chiral units facilitate enantioselectivity by providing specific interaction sites and selective chiral grooves or cavities. Several of these polymers are useful for the separation of enantiomeric diols.

Evaluation of β-cyclodextrin-based chiral stationary phases for capillary column supercritical fluid chromatography

Abstract The Chromatographic performance of two series of chiral stationary phases (CSPs) based on β-cyclodextrin, one copolymeric and one side-arm substituted, was investigated to improve the applicability of cyclodextrin-based CSPs in open-tubular column supercritical fluid chromatography. For the side-arm approach, the influence on performance of different amount of cyclodextrin in the CSP, attachment of the cyclodextrin at the wide or narrow opening, different substituents on the cyclodextrin, the structure of the spacer and the film thickness was studied. The immobilization of these CSPs was also investigated. In addition, the chromatographic performance in gas and supercritical fluid chromatography of one of these CSPs was compared at optimal conditions using test solutes having relatively large differences in size and functionality.

Large-rim-tethered permethyl-substituted β-cyclodextrin polysiloxanes for use as chiral stationary phases in open tubular column chromatography

Abstract 3-O-(p-Allyloxybenzoyl)heptakis(2,6-di-O-methyl)-β-cyclodextrin, which was used for preparation of permethylated 3-O-(p-allyloxybenzoyl)-β-cyclodextrin (4), was produced in a 15% yield by a monoesterification of heptakis(2,6-di-O-methyl)-β-cyclodextrin. Heptakis[6-O-(tert.-butyl)dimethylsilyl]-β-cyclodextrin was regioselectively monoesterified with p-allyloxybenzoyl chloride or p-(tert.-butyl)benzoyl chloride to yield 2-O-(p-allyloxybenzoyl)heptakis[6-O-(tert.-butyl)dimethylsilyl]-β-cyclodextrin (6) or 2-O-[p-(tert.-butyl)benzoyl]heptakis [6-O-(tert.-butyl)dimethylsilyl]-β-cyclodextrin (7). Compound 6 was acylated to give tridecaacetate 8, which was deprotected and methylated, to give 2A-O-(p-allyloxybenzoyl)heptakis(3-O-acetyl-6-O-methyl)- 2B,2C,2D,2E,2F,2G-hexa-O-acetyl-β-cyclodextrin (10). Both 6 and 7 were methylated, following by deprotection and methylation (on the 6-position), to give permethylated 2A-O-(p-allyloxybenzoyl)-β-cyclodextrin (15) and permethylated 2A-O-[p-(tert.-butyl)benzoyl]-β-cyclodextrin (16), respectively. Then, 16 was treated with lithium aluminum hydride to form monoalcohol, which was transformed into permethylated 2A-O-(p-allyloxybenzyl)-β-cyclodextrin (18) by a nucleophilic substitution reaction. Four new permethyl- or per(methyl/acetyl)-substituted β-cyclodextrin-bound methylpolysiloxanes were prepared by a hydrosilylation reaction of the monoalkenyl-substituted β-cyclodextrin derivatives 4, 10, 15 and 18 with a specially prepared hydromethylpolysiloxane. The polymeric phases provide excellent enantiomeric separations of a variety of chiral solutes in open tubular column supercritical fluid chromatography and gas chromatography.

New chiral polysiloxanes prepared from derivatives of (+)- or (-)-2-phenyl-3-butehoic acid, (r)-l-hepten-3-ol and (r)-l-cyclohexyl-2-propen-1-ol

Abstract A series of new polysiloxanes containing chiral side groups has been prepared. These polymers were prepared by hydrosilylating chiral alkene derivatives onto polyhydromethylsiloxane. The alkene derivatives were prepared from (+) or (-)-2-phenyl-3-butenoic acid, (R)-1-hepten-3-ol and (R)-1-cyclohexyl-2-propen-1-ol. Polysiloxanes containing racemic substituents were also prepared fron derivatives of racemic 3-buten-2-ol. The polysiloxanes containing biphenyl carboxylate derivatives (11a–13a) had liquid crystalline properties. These polymers were prepared for use as stationary phases for capillary gas and supercritical fluid chromatography.

Rational design of chiral stationary phases for capillary supercritical fluid chromatography.

Abstract A new class of chiral copolymers consisting of chiral organic and dimethylsiloxane units is described. One example of such copolymers, containing alternating diamide and dimethylsiloxane units, has been synthesized. Using these chiral materials as stationary phases in capillary columns, chiral diols can be efficiently resolved by supercritical fluid chromatography.