Nitrogen lithium diisopropylamide

The vinyl group has been used to protect the nitrogen of benzimidazole during metalation with lithium diisopropylamide. It is introduced with vinyl acetate [Hg(OAc)2, H2SO4, reflux, 24 h] and cleaved by ozonolysis (MeOH, —78°). ... 

The TBDMS derivative of a /3-lactam nitrogen is reported to be stable to lithium diisopropylamide, citric acid, Jones oxidation, and BH3-diisopropylamine, but not to Pb(OAc)4 oxidation. 

An oven-dried. 50-mL, 3-necked flask equipped wilh a pressure-equalizing dropping funnel, reflux condenser, nitrogen inlet, magnetic stirrer, and vacuum takeoff adapter is evacuated (vacuum pump) and refilled three times with nitrogen. 10 mL of THF and 0.735 mL (5.25 mmol) of diisopropylamine are then added via a double-ended needle. The solution is cooled to 0"C and 2.2 mL of a 2.4 M solution of butyllithium (5.25 mmol) in hexane are added. The lithium diisopropylamide is allowed to form at 0 °C for 15 min and is then cooled to — 20 C. 5 mmol of the chiral acyclic ketone iminc in 5 mL of THF are added (5 min) and anion formation allowed to continue for 1 h at 20 C. The anion solution is then heated to reflux for 2 h and cooled to —78 C. A solution of 5.25 mmol of the iodoalkane in 5 mL of THF is then added, and alkylation is allowed to proceed at — 78 °C for 1 h. Workup and hydrolysis, as described for the cyclic ketones (see Section 1.1.1.4.1.2.L), yields the a-alkylatcd acyclic ketones (see Table 4). 

To 10.5 mmol of lithium diisopropylamide in 23 mL of THF at — 78 C under nitrogen are added 3.21 g (10 mmol) of (45,55)-4,5-dihydro-4-melhoxymethyl-5-phenyl-2- 3-(trimethylsilyloxy)propyl]oxazole in lOmL of THF. After the mixture is stirred for 0.5 h, the yellow solution is cooled to —98 C and 1.0 mL (10.5 mmol) of dimethyl sulfale is added neal, dropwise. Stirring is continued for 2 h at 98 G, and then the solution is slowly warmed to r.t. 

Lithium diisopropylamide, 163 Phenyliodine(III) diacetate, 242 Tetrakis(triphenylphosphine)-palladium(O), 289 Trimethylamine N-oxide, 325 Containing one nitrogen—indoles Hexamethyldisilazane-Chlorotri-methylsilane, 141 Iron carbonyl, 152... 

The diketone (15.20 g, 100 mmol) is dissolved in 27 mL of dry tetrahydrofuran in a 50-mL, round-bottomed flask and added dropwise through a 16-gauge cannula (nitrogen pressure) during 35 min to the lithium diisopropylamide solution. This mixture is stirred for 30 min at -78°C and is added in turn to 280.4 mL (300 mmol) of a 1.07 M solution of anhydrous ferric chloride (Note 10) in dry dimethylformamide diluted with 39 mL of dry dimethylformamide and contained in a 1-L, three-necked, round-bottomed flask equipped with an efficient mechanical stirrer and cooled to -78°C (Note 11). This addition is accomplished as rapidly as possible through an 8-gauge cannula... 

Synthesis routes used in the work involved condensation of l-benzyl-4-piperidone with an appropriately substituted propionamide promoted by a strong base (lithium diisopropylamide, LDI), with subsequent alkylation of anilino nitrogen (if necessary) and replacement of N-benzyl by the 2-arylethyl substituent. Direct use of the N-arylethyl-4-piperidone was also made. 

A solution of ethyl 2-ethylbutyrate (150 mmol) dissolved in 25 ml THF was added dropwise to a solution of lithium diisopropylamide (prepared by treating diisopropylamine (165 mmol) dissolved in 150 ml THF with butyllithium in hexanes (165 mmol) at —78°C 1 hour) in a nitrogen atmosphere and stirred 1 hour. Thereafter, bromoacetonitrile (180 mmol) dissolved in 50 ml THF was added over 30 minutes and the mixture stirred overnight at —78°C. The reaction was quenched with 250 ml IM HCl, the layers separated, and the aqueous phase extracted 3 times with 100 ml diethyl ether. The extracts... 

The approach of leveraging chirality at the imine nitrogen to impart enantioselectivity has also been used to advantage in the preparation of chiral heterosubstituted aziridines. Thus, when 2-(l-chloroethyl)-4-methyl-thiazole 671 is deprotonated with lithium diisopropylamide (LDA) and treated with the chiral aldimine 670, the aziridinyl thiazole derivative 672 is produced in excellent yield and diastereoselectivity (Scheme 164) <2004T1175>. 

Enolate (5)—4-Li was generated upon treatment of the heterocycle with lithium diisopropylamide (LDA) in THF solution and under a nitrogen atmosphere. The electrophile was then added at —78 °C to afford the trans-alkylated products with high diastere-oselectivity and in good yields (eq 6, Table 1). 

Lithium diisopropylamide (LDA) is a strong base, but not a good nucleophile because of steric inhibition by the two isopropyl groups directly attached to the nitrogen anion. 

The structural chemistry and solution behavior of lithium diisopropylamide (LiN(CHMe2)2, EDA) typifies the complexities of these systems. Although the base-free compound crystallizes as infinite helical chains with two-coordinate lithium and four-coordinate nitrogen, it is isolated from A,A,A, A -tetramethylethylenediamine (TMEDA)/hexane mixtures as an infinite array of... 

Apart from the bases mentioned a series of other nitrogen bases (ammonia, triethylamine, pyridine, cyclic amidines, lithium diethylamide, lithium diisopropylamide, lithium piperidide, etc.) have been used to deprotonate phosphonium salts. 

---