Study of the Lewis acid-promoted addition of silylenol ethers to imines derived from glyceraldehyde

Chiral N-benzylimines derived form d-glyceraldehyde undergo Lewis acid-promoted asymmetric Mannich reactions with O-methyl-O-trimethylsilyl dimethylketeneacetal to give β-amino acid esters in good yields and with excellent diastereoselectivities.     

Asymmetric addition of dimethylzinc to alpha-ketoesters catalyzed by (-)-MITH

This investigation describes the catalytic asymmetric addition of dimethylzinc to alpha-ketoesters in the presence of (-)-MITH ( 5) and triethyl borate as an additive to give the corresponding chiral alpha-hydroxy esters with good yields and high enantioselectivities.     

Radical addition to oxime ethers for asymmetric synthesis of beta-amino acid derivatives

The diastereoselective alkyl radical addition to chiral oxime ethers was studied with a view to preparing enantiomerically pure alpha,beta-dialkyl-beta-amino acid derivatives. The phase transfer-catalyzed alkylation of Oppolzer's camphorsultam derivative of oxime ether proceeded smoothly to give the alkylated N-(beta-oximino)acyl derivatives. In the presence of BF3.OEt2, radical addition to the oxime ethers proceeded using triethylborane as the radical initiator to give alpha,beta-dialkyl-beta-amino acid derivatives with excellent diastereoselectivity.     

Stereoselective addition of dimethyl thiophosphite to imines

Dimethyl thiophosphite (DMTP) was synthesized from dimethyl phosphite, and the diastereoselective addition of DMTP to benzaldimines bearing chiral auxiliary groups was examined. Yields of the product alpha-aminophosphonothionates ranged from 17% to 75% after chromatography. The addition of DMTP to the benzaldimine derived from (S)-phenylglycinol afforded the highest diastereoselectivity (83:17), whereas addition of DMTP to the benzaldimine derived from threonine methyl ester and alanine methyl ester were far less diastereoselective, affording 38:62 and 61:39 ratios, respectively. Addition of DMTP to the benzaldimine derived from (R)-alpha-methylbenzylamine (78:22) and (S)-serine methyl ester (73:27) were intermediate in selectivity. DMTP addition to the imines formed between serine methyl ester and acetaldehyde and isobutyraldehyde gave 55:45 and 70:30 ratios, respectively, with the diastereoselectivity corresponding roughly to the size of the alpha-alkyl group. The stereochemistry of the newly formed alpha-stereocenters resulting from the addition of DMTP to (S)- and (R)-phenylglycinol benzaldimines was confirmed by conversion of the product alpha-aminophosphonothionates to the known enantiomers of phosphonophenylglycine.     

Peroxide-mediated efficient addition of cycloalkanes to imines

A novel direct addition of cycloalkanes to imines mediated by peroxide was developed. The reaction tolerates a wide range of functionalities as well as aqueous conditions.     

Tin-free radical addition of acyloxymethyl to imines

Acyloxymethyl radicals were generated from the corresponding iodomethyl esters and successfully underwent addition to the CN bond of N-Ts, N-PMP, and N-Dpp imines by the action of dimethylzinc or triethylborane. Ethyl acetate, toluene, and benzene as well as dichloromethane were suitable solvents. The utility of acyloxymethyl radicals as a hydroxymethyl anion equivalent was highlighted by the facile hydrolysis of the acyloxy moiety of the adducts to give the corresponding amino alcohol derivatives in good to high yield.     

Effect of microwave heating in the asymmetric addition of dimethylzinc to aldehydes

Microwave-heated enantioselective additions of dimethylzinc to various aldehydes are reported. Dramatically reduced reaction times and lower catalyst loadings (5%), compared with conventionally used conditions, can be achieved, with excellent yields and just small loss of enantioselectivity (up to 83% enantioselectivity is achieved). In the reaction with aliphatic aldehydes the same enantioselectivity has been achieved for microwave-heated and conventional room temperature conditions.     

Catalytic asymmetric addition of dimethylzinc to alpha-ketoesters, using mandelamides as ligands

[reaction: see text] A strategy based on the control of the electron-donating capabilities of the coordinating groups of the ligand has been applied in the catalytic asymmetric addition of organometallic reagents to ketoesters. Mandelamides having deprotonated alcohol and carboxyamido groups catalyzed the addition of dimethylzinc to alpha-ketoesters with good yields and ee (up to 90%).     

Radical polymerization initiated by Bergman cyclization

The diradical generated by the Bergman cyclization of 3,4-benzocyclodec-3-ene-1,5-diyne is shown to initiate the radical polymerization of several monomers. Methacrylates are polymerized to high molecular weight by the diradical initiator much more efficiently than other monomers. The relation between the rate of polymerization and the degree of polymerization indicates that the polymer primarily propagates as a monoradical. This monoradical growth is in agreement with established theory predicting that diradical initiators can produce high polymer only through chain transfer followed by monoradical growth due to the rapid intramolecular termination of short diradical chains. In agreement with this mechanism, the polymerization rate of acrylonitrile initiated by the diradical is shown to increase by more than 20-fold upon addition of a chain transfer agent. Small molecule products consistent with intramolecular termination of diradical oligomers were isolated, and the structures of these molecules suggest how the diradical self-terminates in the absence of chain transfer.     

Isomerization of allyl ethers initiated by lithium diisopropylamide

Lithium diisopropylamide (LDA) promotes virtually quantitative conversion of allylic ethers to (Z)-propenyl ethers. It was discovered that allylic ethers can be isomerized efficiently with very high stereoselectivity to (Z)-propenyl ethers by LDA in THF at room temperature. The reaction time for the conversion increases with more sterically hindered allylic ethers. Different amides were also compared with LDA for their ability to effect this isomerization.     

Diastereoselective addition of enantiopure lithium tert-butylsulfinylferrocene to imines

(S)-tert-Butylsulfinylferrocene was submitted to ortho-metalation, and the corresponding lithium derivative was trapped by alkyl or aryl imines bearing various electron-withdrawing groups on the nitrogen atom (Ts, Dpp, Boc). New aminosulfoxides were obtained with complete diastereocontrol when Dpp or Boc groups were used. The absolute configuration (SS,SFc,S) has been determined by single-crystal X-ray analysis and chemical correlation. An unusual pseudocyclic boatlike transition state has been proposed to explain the stereochemical course of this reaction.     

Rhodium-catalyzed synthesis of branched amines by direct addition of benzamides to imines

Rhodium-catalyzed addition of benzamide C-H bonds to a range of aromatic N-sulfonyl aldimines has been developed and proceeds with high functional group compatibility. The synthetic utility of the resulting branched amine products has also been demonstrated by the preparation of isoindoline and isoindolinone frameworks.     

Chemoselective addition of organometallics to oxime ethers

In this paper, an efficient method for preparation of various substituted hydroxylamines from aldehydes is reported. We first prepare O-trimethylsilyl oxime ether in 5 M solution of lithiumperchlorate in diethyl ether (LPDE 5M) from condensation reaction between aldehyde and O-trimethylsilyl hydroxylamine, then add organosilane or organotin nucleophile in the same vessel to preparing the corresponding α-substituted hydroxylamines in one-pot synthesis.     

Enantioselective addition of aryllithium reagents to aromatic imines mediated by 1,2-diamine ligands

A variety of optically enriched amines have been obtained by addition of aryllithium reagents to aromatic imines using N,N′-tetramethylcyclohexane-1,2-diamine as chiral ligands. Enantiomeric excesses up to 90% could be obtained.