Configurationally labile enantioenriched lithiated 3-arylprop-2-enyl carbamates: joint experimental and quantum chemical investigations on the equilibrium of epimers.

Experimental investigations as well as high-level quantum chemical calculations are performed on the two epimeric pairs of complexes 4.2 and 6.2 obtained by lithiation of cinnamyl carbamate (1) and 1-naphthyl derivative 5 in the presence of BOX ligands (S,S)- and (R,R)-2.

1-(N,N-diisopropylcarbamoyloxy)-1-tosyl-1-alkenes--a2d1 synthons via tandem umpolung.

1-(N,N-diisopropylcarbamoyloxy)-1-tosyl-alkenes have been developed as an a(2)d(1) synthon via tandem umpolung. Upon addition of Grignard reagents and further quench by carbonyl compounds, this synthon produces alpha,alpha'-branched-alpha'-oxygenated ketones. Strategically, this widely applicable method installs respectively a carbanion unit and a carbonyl unit formally onto the alpha-carbon and the carbonyl center of an aldehyde in one-pot.

Enantiotopos-differentiating (-)-sparteine-mediated gamma-deprotonation of 1-alkenyl carbamates: DFT calculations verify the observed stereoselectivity.

The enantioselective lithiation/gamma-deprotonation of three 1-alkenyl N,N-diisopropylcarbamates 6 by alkyllithium/(-)-sparteine has been modeled by the DFT method B3LYP/6-31G(d). The results of these calculations predict the preferential removal of the gamma-pro-R proton from the precomplexes 7 to give the (S)-lithio derivates 8. The calculations also indicate the necessity of an anion-stabilizing substituent (Ph, -CC-Ph) in the alpha-position of the substrate.

Highly enantioselective reactions of configurationally labile epimeric diamine complexes of lithiated S-benzyl thiocarbamates.

Substitution reactions that employ primary-carbamoyl-protected arylmethanethiols are described. The enantiodetermining step was found to occur in the post-deprotonation step as a dynamic thermodynamic resolution with a chiral bis(oxazoline) ligand. The configurationally labile lithium complexes were trapped with various electrophiles to yield different substitution products in good to excellent yields and enantiomeric excesses.

Configurationally labile lithiated O-benzyl carbamates: application in asymmetric synthesis and quantum chemical investigations on the equilibrium of diastereomers.

The title compounds were generated by deprotonation of different benzyl-type carbamates with sec-butyllithium in the presence of chiral diamines (-)-sparteine or diisopropyl and di-tert-butyl bis(oxazoline)s. These lithiated species exhibit configurational lability at -78 degrees C. In the case of the chiral di-tert-butyl bis(oxazoline), the equilibrium of the epimeric complexes can be used synthetically to obtain highly enantioenriched secondary benzyl carbamates.

Highly diastereoselective lithiation and substitution of an (S)-prolinyl thiocarbamate via sterically homogeneous lithio(thiocarbamate): synthesis of enantiomerically pure prolinethiols.

Highly diastereoselective lithiation-substitution reactions of an (S)-proline derived S-alkyl thiocarbamate was accomplished. The configuration of the predominant alkyllithium species and the stereochemical course of the electrophilic substitution reactions are deduced by a combination of X-ray crystal structure analysis, NMR spectroscopic studies, deuteration/dedeuteration experiments, and quantum chemical calculations. The lithium intermediate (S,S)-9 was found to be kinetically and thermodynamically favoured, whereas (S,R)-9 rapidly epimerizes.

Asymmetric synthesis of 3-hydroxy-pyrrolidines via tin-lithium exchange and cyclization.

We report a method for the synthesis of chiral pyrrolidines using tin-lithium exchange and cyclization reactions. The precursors are formed readily from simple starting materials and undergo tin-lithium exchange by treatment with n-butyllithium. Subsequent intramolecular carbolithiation is stereoselective to give highly enantiomerically enriched pyrrolidines in excellent yields.

Highly diastereoselective formation and reactions of a non-mesomerically stabilized, lithiated alpha-thiocarbanion.

A new class of non-mesomerically stabilized, unbranched, configurationally stable lithiated alpha-thiocarbanion has been synthesized and its stereospecific reactions with several electrophiles were investigated.

Asymmetric gamma-deprotonation and homoaldol reaction of 1,3-dien-2-yl carbamates: stereo- and regiochemistry.

[reaction: see text] Lithium compounds 7 are configurationally stable intermediates obtained by deprotonation of 1,3-dien-2-yl carbamates 6 with n-butyllithium/(-)-sparteine with a high degree of enantiotopic differentiation at the gamma-position. They react with electrophiles regioselectively giving highly enantioenriched products. Starting with different isomers or changing the double-bond geometries in 6 leads to either of the enantiomers.

3,3'-oxazolidinyl-substituted 2,2'-biphenyldiols: novel tropos ligands with a large induction on the chiral axis.

A novel type of bisphenol ligand is presented which provides high modularity. Chiral information is introduced in the 3,3'-positions as N-arenesulfonyl-1,3-oxazolidines inducing an unexpectedly high diastereoselectivity of up to 98:2 onto the chiral axis. The impact of each part of the molecule on the diastereomeric ratio is evaluated with extended variable-temperature (VT) NMR studies.

Substitution of hydroxybiaryls via directed ortho-lithiation of N-silylated O-aryl N-isopropylcarbamates.

[reaction: see text] Herein we report regioselective substitution reactions of a series of 2- and 3-hydroxybiaryls including BINOL via a new directed ortho-metalation procedure. O-Aryl N-isopropylcarbamates, conveniently prepared from phenols and isopropyl isocyanate, are temporarily and in situ N-protected by means of silyl triflates to form stable intermediates for low temperature lithiation reactions using butyllithium/TMEDA in diethyl ether. The resulting aryllithiums are efficiently substituted by a wide range of electrophilic reagents to afford functionalized biaryls in high yields.

Enantioselective lithiation of O-alkyl and O-alk-2-enyl Carbamates in the presence of (-)-sparteine and (-)-alpha-isosparteine. A theoretical study.

Quantum chemical DFT calculations at the B3LYP/6-31G(d) level have been used to study the enantioselective lithiation/deprotonation of O-alkyl and O-alk-2-enyl carbamates in the presence of (-)-sparteine and (-)-alpha-isosparteine. Complete geometry optimization of the precomplexes consisting of the carbamate, the chiral ligand, and the base (iPrLi), for the transition states of the proton-transfer reaction, and for the resulting lithio carbamates have been performed in order to quantify activation barriers and reaction energies. For the lithiodeprotonation of ethyl carbamate 12 in the presence of (-)-sparteine (5) the preferred abstraction of the pro-S proton (by 2.

Stereoselective synthesis of Baylis-Hillman-type adducts via allenolates generated by acyl migration.

[reaction: see text] The rearrangement of the carbamoyl group in allenyl carbamate 1 in the presence of n-BuLi in situ generates the allenolate 3, which is subsequently intercepted with aromatic aldehydes furnishing (Z)- or (E)-configured Baylis-Hillman-type adducts 4 or 5. The double bond isomers can be interconverted by a retro aldol-type reaction.

Total synthesis of (-)-alpha-kainic acid by (-)-sparteine-mediated asymmetric deprotonation-cycloalkylation.

[reaction: see text] We report a new enantioselective synthesis of (-)-alpha-kainic acid from d-serine methyl ester hydrochloride, based on a (-)-sparteine-mediated asymmetric deprotonation of an intermediate carbamate that, by stereospecific anti S(N)'S(E)' intramolecular cycloalkylation, leads to the pyrrolidine ring precursor of (-)-alpha-kainic acid, in high yield and diastereoselectivity. The intermediate pyrrolidine was further transformed to (-)-alpha-kainic acid in three steps.

Highly enantioenriched homoenolate reagents by asymmetric gamma-deprotonation of achiral 1-silyl-substituted 1-alkenyl carbamates.

1-trimethylsilyl-1-alkenyl carbamates 1 are deprotonated by n-butyllithium/(-)-sparteine (2) with a high degree of enantiotopic differentiation in the gamma-position to form the enantiomerically enriched allyllithium derivatives 3. Trapping these with several electrophiles proceeds stereospecifically in an anti-S(E)' or syn-S(E)' substitution to form products 4 or ent-4, respectively. Compounds 3a (R = Me) and 3b (R = Ph) exhibit toward carbonyl electrophiles opposite senses of almost complete stereospecificity, thus for 3b.

Synthesis of enantiomerically enriched tertiary 2-cyclohexene-1-thiols via configurationally stable alpha-thio-substituted allyllithium compounds.

[reaction: see text] (S)-S-(2-Cyclohexenyl) N,N-diisopropylmonothiocarbamate [(-)-(S)-8] was deprotonated by sec-butyllithium/TMEDA to form a configurationally stable lithium compound (S)-9, which is the first example of a new class of alpha-thio-substituted organolithium compounds with improved properties. It is regioselectively alkylated by alkyl halides with complete stereoinversion to form the monothiocarbamates (+)-10 which afford highly enantioenriched tertiary 2-cyclohexene-1-thiols (+)-6 on reductive cleavage.

Synthesis of an ethynyl carbamate and application for enantioselective cyclocarbolithiation.

[reaction: see text] The intramolecular trans-cyclocarbolithiation of the alpha-lithiated 4-substituted 5-hexynyl carbamate (1S,4RS)-14 employing lithiodestannylation is presented. The 5-exo-dig cyclization products cis-/trans-16a were formed exclusively. The highly enantioenriched organotin precursor (S)-11 was synthesized via an asymmetric deprotonation of the corresponding alkyl carbamate 10 by the chiral complex sec-butyllithium/(-)-sparteine and subsequent substitution with tributyltin chloride.

Asymmetric synthesis of 2-alkenyl-1-cyclopentanols via tin-lithium exchange and intramolecular cycloalkylation.

[reaction: see text] We report a method for the synthesis of chiral cyclopentanes using tin-lithium exchange and cycloalkylation reactions. The sec-butyllithium/(-)-sparteine-mediated deprotonation of an alkyl carbamate and subsequent substitution furnishes a highly enantioenriched stannane as a stable carbanion equivalent. It was transformed into suitable cyclization precursors, which underwent tin-lithium exchange and stereoselective cycloalkylation when reacted with n-butyllithium, giving highly enantioenriched cyclopentanes in very good yields.

Planar-chiral (2E,7Z)- and (2Z,7E)-cyclonona-2,7-dien-1-yl carbamates by asymmetric, bis-allyic, alpha, alpha'-cycloalkylation--studies on their conformational stability.

Enantiomerically enriched (>80 % ee) (M,1R,2Z,7E)- and (M,1R,2E,7Z)-cyclonona-2,7-dienyl carbamates have been synthesized by an intramolecular cycloalkylation of the corresponding 1-lithio-9-chloronona-2,7-dienyl carbamates. The enantioenriched precursors were generated by asymmetric deprotonation of the dienyl carbamates by means of n-BuLi/(-)-sparteine. The primarily obtained cyclononadienes, each bearing one element of planar and centre chirality, were formed by an , coupling of both allylic moieties.