Marek Zaidlewicz

Dual Stereoselectivity in the Dialkylzinc Reaction Using (−)-β-Pinene Derived Amino Alcohol Chiral Auxiliaries

(+)-Nopinone, prepared from naturally occurring (-)-beta-pinene, was converted to the two regioisomeric amino alcohols 3-MAP and 2-MAP in very good yield and excellent isomeric purity. Amino alcohol 3-MAP was synthesized by converting (+)-nopinone to the corresponding alpha-ketooxime. This was reduced to the primary amino alcohol and was converted to the morpholino group through a simple substitution reaction. 3-MAP was characterized by X-ray crystallography, which displayed the rigidity of the pinane framework. Amino alcohol 2-MAP was prepared from its trans isomer 2, which in turn was synthesized via hydroboration/oxidation of the morpholine enamine of (+)-nopinone. Two-dimensional NMR was used to characterize amino alcohol 2-MAP, and NOE was used to confirm its relative stereochemistry. These amino alcohols were employed as chiral auxiliaries in the addition of diethylzinc to benzaldehyde to obtain near-quantitative asymmetric induction in the products. The use of 3-MAP yielded (S)-phenylpropanol in 99% ee, and its regioisomer 2-MAP gave the opposite enantiomer, (R)-phenylpropanol, also in 99% ee. Other aromatic, aliphatic, and alpha,beta-unsaturated aldehydes were implemented in this method, affording secondary alcohols in high yield and enantiomeric excess. Amino alcohols 2-MAP and 3-MAP were also found to be useful in the dimethylzinc addition reaction, both catalyzing the addition to benzaldehyde with nearly quantitative ee. Regioisomeric amino alcohols 2-MAP and 3-MAP, even though they were prepared from one enantiomer of nopinone, provide antipodal enantiofacial selectivity in the dialkylzinc addition reaction. This circumvents the necessity to synthesize amino alcohols derived from (-)-nopinone, which in turn requires the unnatural (+)-beta-pinene. Possible mechanistic insights are offered to explain the dual stereoselectivity observed in the diethylzinc addition reaction involving regioisomeric, pseudo-enantiomeric amino alcohols 3-MAP and 2-MAP.

SYNTHESES WITH ORGANOBORANES. VII. MONOHYDROBORATION OF CONJUGATED DIENES WITH CATECHOLBORANE CATALYZED BY COMPLEXES OF NICKEL(II) CHLORIDE AND COBALT (II) CHLORIDE WITH DIPHOSPHINES

Abstract The monohydroboration of representative conjugated dienes 1–7 with catecholborane in the presence of SmI 3 , t -BuOSmI 2 , LaI 3 , Ti(OPr i ) 4 , iron(II), nickel(II) and cobalt(II) chloride complexes with dppe, dppp and dppb was examined. NiCl 2 (dppe), NiCl 2 (dppp) and CoCl 2 (dppp) showed catalytic activity. The 1,2-addition products were obtained, no 1,4-addition was obseved. The reactivity in the presence of NiCl 2 (dppe) decreased in the order acyclic dienes > cyclic dienes ⪢ 1-decene.

Asymmetric reduction of ketoxime derivatives and N-alkylketimines with borane–oxazaborolidine adducts

Abstract Oxime ethers of acetophenone, isopropyl methyl ketone, and tert-butyl methyl ketone were reduced to the corresponding hydroxylamine ethers of 45–94% ee with borane–oxazaborolidine 1 derived from (−)-norephedrine. A one-pot reduction of acetophenone oxime with 1 to 1-phenylethylhydroxylamine of 87% ee is described. The reduction of 6-methyl-2,3,4,5-tetrahydropyridine and N-methylimines of the above mentioned ketones with borane-B-methyloxazaborolidine adduct 2, derived from (−)-diphenylprolinol, gave the corresponding amines of 40–74% ee.

Synthesis with organoboranes: I. Synthesis of allylic diethylboranes and B-allylic borinanes via metalation of olefins. Contrathermodynamic isomerization of olefins

Abstract Allylic organopotassium compounds prepared by metalation of olefins with trimethylsilylmethylpotassium reacted with chlorodiethylborane and B-chloroborinane to give allylic diethylboranes and B-allylic borinanes, respectively. Hydrolysis of these organoboranes proceeding with allylic rearrangement leads to isomerized olefins. In this way, (E,Z)-2-pentene, (Z)-2-heptene, 1-methylcyclohexene and (+)-α-pinene were cleanly transformed into 1-pentene, 1-heptene, methylenecyclohexane and (+)-β-pinene, respectively. Stereochemistry of the addition of myrtenyldiethylborane to formaldehyde and 2-cyclohexenyldiethylborane to 4-t-butylcyclohexanone is described.

Synthesis of arylboronates by the palladium catalysed cross-coupling reaction in ionic liquids

The palladium catalysed cross-coupling reaction of aryl iodides and bromides with pinacolborane in 1,3-dialkylimidazolium tetrafluoroborates and hexafluorophosphates producing arylboronates is described.

Syntheses with organoboranes. XIII. Synthesis of ω-(4-bromophenyl)alkanoic acids and their borylation

Abstract ω-(4-Bromophenyl)alkanoic acids 2c – e were obtained from 1-bromo-4-alkenylbenzenes 5c – e by hydroboration–thermal isomerization–oxidation. Their esters 11c – e were transformed in good yields into the corresponding boronates 12c – e by the cross-coupling reaction with 4,4,5,5,4′,4′,5′,5′-octamethyl[2,2′]bi[[1,3,2]dioxaborolanyl] ( 10 ) in an ionic liquid, [bmim][BF 4 ]. The use of pinacolborane for the coupling reaction in the ionic liquid gave debromination products, and low yields of 12c – e . Ethyl 3-(4-bromophenyl)propanoate ( 7c ) was transformed into ethyl 3-(4-[1,3,2]dioxaborolanyl)propanoate ( 9c ) by the cross-coupling with [2,2′]bi[[1,3,2]dioxaborinanyl].

Asymmetric synthesis of (S)-bufuralol and a propafenone analogue

Abstract Asymmetric synthesis of ( S )-bufuralol of 87% ee from 3-ethyl-2-hydroxybenzaldehyde, via the reduction of 2-bromo-1-(7-ethylbenzofuran-2-yl)ethanone with (−)- B -chlorodiisopinocampheylborane as the key step, followed by cyclization of the product bromohydrin to the corresponding epoxide and treatment with tert -butylamine, is described. ( S )-1-(3-Phenethylbenzofuran-2-yl)-2-propylaminoethanol of 73% ee, a propafenone analogue, was prepared following the same approach.

Syntheses with organoboranes. IX. Vinyl- and 1-alkenyldichloroboranes as ethylene and 1-alkene equivalents for the Diels–Alder reaction

Abstract Vinyl- and 1-alkenyldichloroboranes were used as dienophiles for the Diels–Alder reaction with representative aliphatic and cyclic 1,3-dienes. The organoborane adducts were transformed into the corresponding olefins either by protonolysis or by oxidation–mesylation–reduction. Direct protonolysis of the adducts gave in most cases mixtures of olefins whereas the reduction of mesylates with lithium triethylborohydride produced pure olefins in good yields.

Syntheses with organoboranes. VI. Kinetic resolution of vinylic epoxides by the reduction with chiral dialkylboranes

Abstract The synthesis of enantiomerically enriched 2-vinyloxirane and monoepoxides of 1,3-cycloalkadienes by kinetic resolution of racemates with Ipc 2 BH, 2- d Icr 2 BH and 4- d Icr 2 BH of high enantiomeric purity is described.

Molecular addition compounds. 14. Convenient preparations of representative dialkylborane reagents using the new, highly reactive N-ethyl-N-isopropylaninine-borane reagent (BACH-EI™)

Abstract Convenient procedures for the preparation of representative dialkylborane reagents, diisopinocampheylborane, [1S]-2-diisocaranylborane, 9-borabicyclo[3,3,1]nonane, dicyclohexylborane and disiamylborane, using the new, highly reactive N -ethyl- N -isopropylaniline-borane reagent (BACH-EI™) in dioxane and tetrahydrofuran are described.