Generation and electrophilic substitution reactions of 3-lithio-2-methyleneaziridines

2-Methyleneaziridinyl anions can be produced by selective deprotonation of the parent aziridine at C-3 using sec-BuLi/TMEDA. Subsequent reaction with a wide variety of electrophiles including MeI, ICH₂CH₂CH₂CH₂Cl, PhCH₂Br, allyl bromide, Me₃SiCl, Bu₃SnCl, PhCHO and Ph₂CO provides the corresponding C-3 substituted derivatives in moderate to good yields (43-91%). In the case of homochiral methyleneaziridines bearing an (S)-α-methylbenzyl group on nitrogen, high levels of diastereocontrol (up to 90%de) can be achieved in this lithiation/alkylation sequence.     

Synthesis of 3-methoxyquinolines via cyclization of 1-isocyano-2-(2-lithio-2-methoxyethenyl)benzenes

2-(2-Isocyanophenyl)acetaldehyde dimethyl acetals were treated with excess LDA to generate 1-isocyano-2-(2-lithio-2-methoxyethenyl)benzenes, which cyclized intramolecularly to afford 3-methoxyquinolines in good to excellent yields.     

C-metallierung an phosphaaromaten - 2-lithio-1-methyl-1,3-benzazaphosphol

1-Methyl-1,3-benzazaphospholes are described; the 2H derivate and t-BuLi give the title compound, characterized by reaction with CO₂ and Me₃SiCl; NMR data confirm the results.     

Theoretical investigation on conformational preferences and structural properties of 2-lithio-1,3-diphosphinane and 2-lithio-1,3-dimethyl-1,3-diphosphinane

A new family of dialphosphacyclohexane is introduced which has three nucleophilic centers. The conformational stabilities and structural properties of 2-lithio-1,3-diphosphinane and 2-lithio-1,3-dimethyl-1,3-diphosphinane were investigated computationally by DFT calculations and NBO analyses at B3LYP/6-31+G(d,p). Relative energy trend in 1,3-diphosphinane and 1,3-dimethyl-1,3-diphosphinane conformations explored from steric and hyperconjugative point of view. The stability trend of 2-lithio derivatives based on calculated relative energies in 1,3-diphosphinane is 1d > 1f > 1b > 1a > 1c > 1e and for 1,3-dimethyl-1,3-diphosphinane derivatives is 2f > 2d > 2b > 2a > 2c > 2e. Calculated NBO atomic charges indicate that high positive charge at lithium and small C–Li Wiberg bond indexes in these derivatives are demonstrators of ionic nature of the C–Li bonds. Stereoelectronic interactions, polarizability of phosphorus, and chelate formation between each of phosphorous and lithium are determining factors in stability trend observed in these derivatives. Ease of lithiation in bis(dimethylphosphino)methane, 1,3-diphosphinane, and 1,3-dimethyl-1,3-diphosphinane derivatives was estimated and compared by isodesmic reaction.     

The formation of open-chain thioesters in the reaction of 2-lithio-2-methyl- and 2-lithio-2-phenyl-1,3-dithiane with chlorodiphenylphosphane followed by oxidation

The unexpected formation of open-chain thioesters (3) and (6) from the reaction of 2-lithio-r-2-t-4-t-6-trimethyl (1-Li) and 2-lithio-r-2-phenyl-t-4-t-6-dimethyl-1,3-dithiane (4-Li), respectively, with chlorodiphenylphosphane followed by oxidation was observed instead of the anticipated gem-derivatives. The X-ray diffraction analysis of (6) and the trapped intermediate (10) confirmed the structure and the proposed mechanism of formation of the open-chain products.     

Some reactions of 1-lithio-2-n-butyl-1,2-dihydropyridine. VI. Synthesis of β-substituted pyridines

Reaction of the ambident anion 1-lithio-2-n-butyl-1,2-dihydropyridine ( 1 ) with several electrophilic reagents has been investigated. Direct methods for the introduction of amino, bromo, β-pyridyl, arylselenyl, alkanesulfonyl and methyl substituents into the β-position of pyridine are described.     

Rotation and inversion barriers in 2-lithio-2-phenyl-1,3-dithianes

The barriers to phenyl rotation in 2-lithio-2-phenyl-cis-4,6-dimethyl-, 2-lithio-2-phenyl-4,4,6-trimethyl- and 2-lithio-2-phenyl-trans-4,6-dimethyl-1,3-dithiane are compared in tetrahydrofuran (THF) and hexamethylphosphortriamide (HMPA). In the first two cases, the barriers in THF are lower than those in HMPA, presumably because the lithio compound exists as a tight ion pair in THF but as a solvent-separated ion pair (with more delocalization of charge into the phenyl ring) in HMPA. However, in the trans-4,6-dimethyl compound the barriers are the same in the two solvents and nearly equal to the barriers for ring reversal. It is concluded that in this compound the rate-determining step for phenyl rotation may actually be ring reversal, at least in solvent HMPA.     

2-Bis (dimethylamino)phosphinoyl-1-lithio-1, 2, 3, 4-tetrahydroisoquinoline. A highly nucleophilic d1-reagent for the preparation of 1-substituted tetrahydroisoquinolines

The title compound 4 is generated from the phosphoric amide 5 in tetrahydrofuran with butyllithium. The lithium reagent 4 is stable at room temperature; its reactions with electrophiles furnish the products 6–22 , 26 , 27 , see Table 1 and the Scheme. A second alkylation is also possible, see 23–25 . The cleavage to tetrahydroisoquinolines is accomplished in refluxing aqueous-methanolic hydrochloric acid, see Table 2. Phosphinoylation, lithiation, reaction with electrophiles and cleavage constitute an efficient sequence for 1-alkylation of the isoquinoline nucleus.     

The generation of 2-lithio-1,3-butadiene and its reaction with aldehydes

2-Lithio-1,3-butadiene has been generated by the Shapiro reaction. It reacts with a range of aldehydes to give 2-substituted butadienes.     

2-lithio-2-phenylsulfonyl propane as efficient precursor of gem-dimethyl cyclopropane carboxylic acids

2-Lithio-2-phenylsulfonyl propane has been successfully used for the cyclopropanation of electrophilic olefins and plays the role of an alkylidene transer reagent.     

Generation and reactions of 2-lithio-2-substituted-1,3-benzodithioles; new,convenient acyl carbanion equivalents

The reaction ofBuⁿLi with 2-substituted-1,3-benzodithioles yields anions which react predictably with organic electrophiles to yield products in which the protected carbonyl group is readily unmasked. The anions constitute useful acyl carbanion equivalents.     

Synthesis and X-Ray Structure of Bis{S-(1-lithio-3,3-diphenylprop-2-enyl)-N-methyl-S-phenylsulfoximine– Tetrahydrofuran (1/2)} Complemented by Model ab initio Calculations of α-Lithiosulfoximines

The gas-phase structure of N,S,S-trimethylsulfoximine 1 and of its monolithiated isomers 2–4 was calculated by ab initio methods. It was found that a Li? C? S? N four-membered chelate 2 is the most stable isomer. The second minimum 4 shows N? Li? O complexation and is only slightly higher in energy. Li-Contacts with the C(α) atom and the sulfoximine O-atom in 3 are energetically disfavored by 6.1 kcal/mol. The two transition states 5 and 6 suggest an interconversion mechanism of 2 to 3 with 4 as an intermediate. A comparison of 4 with the crystal structure of the THF solvate 7 , which was prepared by the addition of BuLi to (±)-S-(3,3-diphenylprop-2-enyl)-N-methyl-S-phenylsulfoximine ( 8 ) at low temperature in THF, demonstrates that the coordination geometry in the solid state is in good agreement with the calculated structure. The (1-lithioallyl)sulfoximine 7 crystallized as a centrosymmetric dimeric aggregate featuring an eight-membered ring with the atomic sequence (Li? N? S? O)₂. The O-atoms of two THF molecules and the sulfoximine O- and N-atoms are coordinated to the Li-atom in a tetrahedral orientation. After metallation, a significant shortening of the S? C(α) bond is observed. Remarkably, only one of the two possible diastereoisomeric enantiomer pairs is found in the solid state.     

Anionic rearrangements starting with 1-lithio-2-propynyl silyl ethers a route to (β-trimethylsilylvinyl) silyl ketones

The title compounds undergo silyl-Wittig rearrangement at low temperature and lead to allenolates at room temperature.