Iridium-catalyzed asymmetric trans-selective hydrogenation of 1,3-disubstituted isoquinolines

The development of the first asymmetric trans-selective hydrogenation of 1,3-disubstituted isoquinolines is reported. Utilizing [Ir(cod)Cl]₂ and a commercially available chiral Josiphos ligand, a variety of differentially substituted isoquinolines are hydrogenated to produce enantioenriched trans-tetrahydroisoquinolines in good yield with high levels of enantioselectivity. Directing group studies demonstrate that the hydroxymethyl functionality at the C1 position is critical for hydrogenation to favor the trans-diastereomer. Preliminary mechanistic studies reveal that non-coordinating chlorinated solvents and halide additives are crucial to enable trans-selectivity.

trans-Selective asymmetric hydrogenation of 1,3-disubstituted isoquinolines.     

Aminothiocarbamate-catalyzed asymmetric bromolactonization of 1,2-disubstituted olefinic acids

An efficient and enantioselective bromolactonization of 1,2-disubstituted olefinic acids using an amino-thiocarbamate catalyst has been developed, resulting in the formation of δ-lactones containing two chiral centers with up to 99% yield, 95% ee.     

Zinc-mediated chain extension reaction of 1,3-diketones to 1,4-diketones and diastereoselective synthesis of trans-1,2-disubstituted cyclopropanols

[reaction: see text] A variety of 1,3-diketones can be efficiently converted into the corresponding 1,4-diketones and trans-1,2-disubstituted cyclopropanols by using organozinc species in one-pot reactions. It was found that 2.3 equiv of CF3CO2ZnCH2I was effective to give the corresponding chain-extended products in 44-85% yields, while a mixture of organozinc species formed from 4.0 equiv of Et2Zn, 2.0 equiv of CF3CO2H, and 4.0 equiv of CH2I2 resulted in the formation of trans-1,2-disubstituted cyclopropanols with quite good yields and diastereoselectivity.     

Synthesis of chiral binaphthalenes using the asymmetric Suzuki reaction

The synthesis of atropisomeric 1,1′-binaphthalenes can be achieved using an asymmetric Suzuki cross-coupling reaction. The Suzuki reaction leading to such hindered compounds is challenging and competing hydrolytic deboronation frequently dominates unless carefully chosen conditions are employed. The simple, standard mechanism is inadequate when describing the Suzuki coupling of hindered partners. Evidence suggests that the key step leading to asymmetry is transmetallation (delivery of the organometallic by the asymmetric ligand) and the reactions operate under kinetic control. Reductive elimination (itself likely to be triggered by oxidative addition of another molecule of halide) is fast compared with equilibration (epimerisation and/or cis-trans isomerisation).     

Nucleophilic substitutions on bromotriazolopyridines - an improved route to 2,6-disubstituted pyridines and to 1,3-disubstituted isoquinolines

A regiospecific synthesis of 2,6-disubstituted pyridines and of 1,3-disubstituted isoquinolines is described.     

Synthesis of 4,6-disubstituted pyrimidines via Suzuki and Kumada coupling reaction of 4,6-dichloropyrimidine

A series of 4,6-disubstituted pyrimidines were synthesized via Suzuki and Kumada coupling reaction of 4,6-dichloropyrimidine.     

Preparation of 1,3-disubstituted isoquinoline derivatives from N-boc-3-substituted-1,2-dihydroisoquinolines

3-Substituted N-Boc-1,2-dihydroisoquinolines 2 can be functionalized at the 1-position via lithiation and subsequent electrophilic trapping. The resulting products 3 can be deprotected and oxidized to afford the corresponding 1,3-disubstituted isoquinolines 5 . Deprotection of dihydroisoquinoline 3k followed by sodium borohydride reduction affords the cis-1,3-disubstituted tetrahydroisoquinoline 11 . The 1,3-disubstituted N-Boc-1,2-dihydroisoquinoline 3g is efficiently alkylated at the 1-position to give 1,1,3-trisubstituted analogs 12 .     

1,3-Dipolar cycloadditions. Reactions of nitrile imines with 1,2-disubstituted alkenes

Nitrile imines react with 1-phenylsulphonyl-2-benzoyl (or methoxycarbonyl)alkenes to give 4-phenylsulphonyl-5-benzoyl (or methoxycarbonyl) substituted pyrazolines. The cycloaddition regioselectivity is discussed in terms of Frontier Orbital energies and coefficients.     

1,2- versus 1,3-Silyl migration in the reaction of acylsilanes with silyl-substituted carbanions

The Peterson olefination of acylsilanes 1 by silylated carbanions 5,14 to give alkenes 13,17 via a 1,3-silyl shift is favored by the stabilization of the carbanion intermediate 16 through two sulfide units versus one as in 12, while a combination of DMPS on 1 and TBS on 14 leads to 1,2-migration product 15.     

Ligand controlled cobalt catalyzed regiodivergent 1,2-hydroboration of 1,3-dienes

Regiodivergent 1,2-hydroboration of 1,3-dienes with pinacolborane has been accomplished by well-defined cobalt complexes of different bidentate ligands. The iminopyridine-cobalt system is selective for Markovnikov 1,2-hydroboration to form allylboronates, while the FOXAP-cobalt(FOXAP=(S)-1-(diphenylphosphino)-2-[(S)-4-isopropyloxazolin-2-yl]ferrocene) catalyst effects the complementary anti-Markonikv 1,2-hydroboration to afford homoallyboronates with high regioselectivity.     

Rate constants for the gas-phase reaction of ozone with 1,2-disubstituted alkenes

The gas-phase reaction of ozone with eight 1,2-disubstituted alkenes has been investigated at ambient temperature (T = 286–296 K) and p = 1 atm. of air. The reaction rate constants, in units of 10⁻¹⁸ cm³ molecule⁻¹s⁻¹, are 144 ± 17 for cis-3-hexene, 157 ± 25 for trans-3-hexene, 89.8 ± 9.7 for cis-4-octene, 131 ± 15 for trans-4-octene, 114 ± 13 for cis-5-decene, ≥ 130 for trans-5-decene, 38.3 ± 5.0 for trans-2.5-dimethyl-3-hexene, and 40.3 ± 6.7 for trans-2.2-dimethyl-3-hexene. Substituent effects on alkene reactivity are examined. Cis-1,2-disubstituted alkenes are less reactive than the corresponding trans isomers. The 1,2-disubstituted alkenes that bear bulky substituents (substitution at the 3-carbon) are ca. 3 times less reactive than the corresponding n-alkyl substituted compounds. The atmospheric persistence of 1,2-disubstituted alkenes is briefly discussed. © 1996 John Wiley & Sons, Inc.     

Regioselectivity-reversed asymmetric aldol reaction of 1,3-dicarbonyl compounds

Reverse regioselectivity: The first catalytic asymmetric C-1 functionalization of 1,3-dicarbonyl compounds by an aldol reaction is described, which regioselectively affords 6-hydroxyhexane-2,4-dione derivatives as the only product with high optical purity of up to 93?%?ee. Furthermore, this method provides a facile access to enantioenriched oxygen-containing spirooxindoles and spirobutyrolactones from simple commercial available starting materials.     

Preparation of polymer-bound 1,2 - and 1,3 - diamines

Two modified copolymers were used for the preparation of polymer bound symmetrical aliphatic diamines using phase transfer catalysis (P.T.C.). These compounds are potential ligands for transition metal ions.     

Lipase-catalyzed asymmetric desymmetrization of prochiral 2,2-disubstituted 1,3-propanediols using 1-ethoxyvinyl benzoate

The lipase-catalyzed asymmetric desymmetrization of the prochiral 2,2-disubstituted 1,3-propanediols was studied using various types of 1-ethoxyvinyl esters (1a-i). Although 1a-e with aliphatic acyl groups were not sufficient, use of the benzoate (1f) in combination with Candida rugosa lipases converted acyclic diols (2, 6) and cyclic diols (11-14) to the optically active compounds (3f, 7f, 15f-18f), bearing a quaternary carbon center, with moderate-to-high optical yields. These products were fairly stable against racemization under acidic conditions.     

1,2- and 1,3-diphosphetanes from alkylidenephosphines

Abstract

Alkyl- or arylbis(trimethylsilyl)phosphines as well as tris(trimethylsilyl)phosphine and the corresponding arsines react with acyl chlorides to give [1-(trimethylsiloxy)alkylidene]phosphines 1 and -arsines 2; most of their 2,2-dimethylpropylidene derivatives are thermally stable at room temperature. With the same class of phosphines as starting compounds and carbon disulfide [bis(trimethylsilylsulfano)methylidene]phosphines 3 are formed, whereas [(dialkylamino)methylidene]-4 and [diarylmethylidene]phosphines 5 or the corresponding arsines 6 and 7 can be obtained from acyl amides or ketones.¹     

Synthesis of 2,5-disubstituted pyrroles by the reaction of ketoximes with 1,2-dibromopropane

Conclusions The reaction of ketoximes with 1,2-dibromopropane in the KOH-DMSO system gave 2,5-disubstituted pyrroles in 21–56% yield.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 9, pp. 2175–2177, September, 1988.     

One-pot asymmetric synthesis of 2- and 2,3-disubstituted tetrahydrofuran derivatives

A novel and convenient one-pot asymmetric synthesis of 2- and 2,3-disubstituted tetrahydrofurans has been achieved in 56-81% yields and 86-99% ee from aliphatic and aromatic aldehydes via an allyl/crotyl/alkoxyallylboration-hydroboration-iodination-cyclization reaction sequence.     

Synthesis of 1,4-disubstituted 1,2,3-triazoles based on cobalt bis(1,2-dicarbollide)

An approach to the synthesis of new 1,4-disubstituted 1,2,3-triazoles, in which one or both substituents contain the cobalt bis(1,2-dicarbollide) fragment, was suggested based on the 1,3-dipolar cycloaddition of azides to alkynes catalyzed by copper(I) compounds. The reaction of cobalt bis(1,2-dicarbollide) azido derivatives with different terminal acetylenes led to 1,2,3-triazoles with the [((CH₂)₂X(CH₂)₂O-C₂B₉H₁₀)Co(C₂B₉H₁₁)] (X = O or CH₂) substituent at position 1 and the organic substituent at position 4. The [3+2] cycloaddition reaction of cobalt bis(1,2-dicarbollide) alkynyl derivatives with methyl azidoacetate furnished isomeric 1,4-disubstituted 1,2,3-triazoles with the metallacarborane fragment at position 4. 1,2,3-Triazole with metallacarborane substituents at positions 1 and 4 containing 36 boron atoms was also synthesized.