M-Butyllithium

To 5.4 mmol of LDA, prepared in 25 mL of diethyl ether from diisopropylamine and 2 M butyllithium in hexane, are added 847 mg (5.00 mmol) of 2-(trimethylsilyloxy)-3-pentenenitrile in 10 mL of diethyl ether at — 78 "C. After stirring for 45 min, 671 mg (5.00 mmol) of 2-phenylpropanal, dissolved in 10 mL of diethyl ether are added. After stirring for 2 h at — 78 X, 1.20 g (10.5 mmol) of trifluoroacetie acid are added carefully to the mixture at below —70CC. 15 mL of sat. aq NH4C1 and then diethyl ether are added and the reaction mixture is allowed to reach r.t. The phases are separated and extracted with aq NH,CI and... 

F,)-2-Rutenvlpotassium Typical Procedure13 To a — 78 C mixture of 22.4g (200mmol) of /-BuOK in 150 mL of dry THF under argon arc added 23 mL (225 mmol) of (L )-2-butcnc. 80 mL (200 mmol) of 2.5 M butyllithium in hexane are then added dropwise at a rate such that the internal temperature does not rise above —65 °C. After completion of the addition, the bath temperature is allowed to rise until the internal temperature reaches — 50 C. The solution is maintained at —50 l C for exactly 15 min and then is immediately recooled to — 78 "C. Temperature control is critical since (/7)-2-buteny(potassium is less stable than, and readily isomcrizes to, (Z)-2-butenylpotassium at this temperature15. 

Z)-2-Butenylpotassium is generated from 4.5 mL (50 mmol) of (Z)-2-butene, 2.8 g (25 mmol) or /-BuOK. and 10.8 mL (25 mmol) oT 2.3 M butyllithium in THF for 15 min at —45 JC. This solution is cooled to — 78 C and 30 mmol of a 1 M solution of methoxy(diisopinocampheyl)borane in diethyl elher is added dropwise. The mixture is stirred for 30 min at — 78 °C, then is treated with 4mL (33 mmol) of boron trifluoride-diethyl ctherate complex this removes methoxide from the intermediate ate complex. This solution is immediatelv treated with 35 mmol of an afdchyde. Isolated yields of homoallylic alcohols are 63-79%. 

A suspension of lithium methoxide (prepared from 1.00 g (31.2 mmol) of methanol in 50 mL of THF and 17.7 mL (27.2 mmol) of 1.54 M butyllithium in hexane) is transferred via a cannula into a — 78 C sol ution of 5.86 g (27.1 mmol) of 2-[(/ )-(/T)-1-chloro-2-butenyl]-4,4,5,5-tctramethyl-l,3,2-dioxaborolane in 100 mL of THF. The solution is warmed, becoming homogeneous at 0 JC, and stirred for 1 h. Solvents arc removed in vacuo and the residue dissolved in 150 mL of petroleum ether (bp 40 -60 °C). This solution is washed with a citric acid/boric acid/phosphate buffer (pH 3) until the aqueous phase shows a pH of 4. The aqueous phase is extracted with 50 mL of petroleum ether (bp 40 - 60 rC). The combined organic extracts are dried over MgS04 and concentrated in vacuo to give a slightly tan oil yield 5.34 g (90%) ca. 90% ee. 

To a —78 C solution of 23.1 mL (100 mmol) of triisopropyl borate and 8.15 mL (110 mmol) of 3-chloro-l-propene in 100 inL of dry THF is added dropwisc via a cannula over 0.5 h a solution of LDA (110 mmol prepared in 200 mL of THF from 110 mmol of diisopropylamine and 47.9 mL of 2.3 M butyllithium in hexane), This mixture is stirred for an additional 0.5 h at — 78 "C then a solution of 75.9 ntL of 2.9 M anhyd hydrogen chloride in diethyl ether is added and the mixture is allowed to warm to 25 °C. The mixture is concentrated in vacuo (20 Torr) and the residue extracted with three 100-mL portions of pentane, Filtration under nitrogen followed by distillation under reduced pressure provides 18.0 g (88%) of diisopropyl l-chloro-2-propenylboronate bp 95-96 "C/25 Torr. Transesterification of this intermediate with 1.3-propanediol provides the title compound in almost quantitative yield bp 110-112°C/20Torr. 

A copper-mediated cyclization of metallated thiophenes has been utilized to prepare polycyclic thiophenes and thiophene cyclophanes. Treatment of dibromide 106 in succession with M-butyllithium (halogen-metal exchange), zinc chloride (transmetallation), and copper chloride gave 7//-cyclopcnta[ 1,2-fc 4,3-6 dithiophene (107) <00H(52)761>. This conversion has also been achieved using a palladium-mediated cyclization performed in the presence of hexamethylditin . Copper-mediated cyclizations have also been applied to the syntheses of cyclopenta[2,l-6 3,4-A ]dithiophen-4-one (108) (three steps from 73) <00S1253> and cyclophane 109 <00CC2329>. 

Butyllithium was purchased from Aldrich Chemical Company, Inc. If fresh, it may be used directly without titration otherwise it should be titrated.2 More dilute and/or more concentrated (i.e., 2.5 M) butyllithium in hexanes can be used without altering the yield. 

This complex was generated by treatment of ligand 2, for example, with M-butyllithium followed by addition of 0.5 equiv of copper(II) chloride. This species was purified by column chromatography and used in 1 mol % (relative to ethyl diazoacetate) in the reaction between styrene (3 equiv) and ethyl diazoacetate (1 equiv). The results of these experiments are summarized in Table 9.1 (Fig. 9.11). As can be seen from these results, the yields range from 72-88%, the trans/cis ratios are all approximately equal ( 70 30), but the enantioselectivities for the isomers... 

To a solution of 1.97 g (10 mmol) of 2-butynyl diisopropylcarbamate in 30 mL of diethyl ether under nitrogen at —78 °C are added 6.9 mL (11 mmol) of 1.6 M butyllithium via a syringe. After 15 min at — 70 °C, 3.12 g (11 mmol) of titanium(IV) isopropoxide in hexane are added and the mixture is stirred for 1.5 h at between — 70 and — 78 C. After raising the temperature to 0 °C the reaction mixture is poured into a mixture of 50 g of ice, 50 mL of 2 M hydrochloric acid and 100 mL of diethyl ether. The aqueous layer is extracted with two 50-mL portions of diethyl ether, and the ethereal solutions are washed with 50 mL of water, 50 mL of sat. aq NaHCOj/KCl and dried over MgS04. The solvent is evaporated in vacuo and the residue purified by column chromatography over silica with diethyl ether/hexane 1 5 as eluant yield 2.15 g (89%) mp 48 C. 

A solution of lithium benzyloxide is prepared by addition of 56 mL (90 mmol) of 1.6 M butyllithium in hexane to 9.2 mL (88 mmol) of benzenemethanol in 100 mL of THF at — 78 C, followed by the addition of rigorously anhyd DMSO. This solution is added to a solution of 16.38 g (71.7 mmol) of (S)-pinanediol (chloromethyl)boronatc in 60 mL of THF stirred at — 78 °C. The mixture is allowed to warm to r.t. and then heated at 45-50rC for 3 h, at which time TLC indicates the reaction is complete. The mixture is worked up by acidificalion with 0.5 M aq hydrochloric acid followed by diethyl ether extraction. The diethyl ether, DMSO, and benzenemethanol are distilled under vacuum and the residue is chromatographed on silica gel with 10% ethyl acetate in hexane. The product is distilled, and solidifies on cooling vield 19.8 g (92%) bp 158-162 °C (0.2 Torr) mp 25-27°C. 

A solution of LDA is prepared by the addition of 12 mmol of 1.6 M butyllithium in hexane to a stirred solution of 1.5 g (15 mmol) of diisopropylaminc in 15 mL of THF at 0°C, then cooled to —78 °C. A solution of 10 mmol of the benzyloxy boronic ester and 10-17 g (60-100 mmol) of dibromomethane is stirred at — 78 °C during dropwise addition of the LDA solution via a cannula. The solvent is distilled at <0.75 Torr <0 °C. The solid residue of borate complex is cooled to — 78 CC and treated with a 0.5-0.7 M solution of anhyd zinc chloride (Section 1.1.2.1.1.1.) [(1 On + 8) mmol, where n is the number of benzyloxy groups in the boronic ester] in THF. The mixture is stirred for 16-20 h at 20-25 °C. An equal volume of petroleum ether (bp 30-60 °C) is added, followed by 100 mL of sat. aq NH4C1. The aqueous phase is further extracted with 4 1 petroleum cthcr/diethyl ether, and the combined organic phase is filtered through a 5-cm column of MgS04 with the aid of additional petroleum ether/diethyl ether. After concentration, the residue of labile a-bromo boronic ester should be used promptly in the next step. 

A. Lithium triethylcarboxide (Solution 1). A thoroughly dried, 1-1., three-necked, round-bottomed flask is fitted with a septum inlet with serum cap, a reflux condenser, and a magnetic stirrer. The flask is purged with and maintained under an atmosphere of dry nitrogen. A solution of 300 ml. of 1.66 M butyllithium (0.50 mole) in hexane (Note 1) is introduced into the flask by syringe (Note 2) and cooled to 0° in an ice bath. Then 58 g. (0.50 mole) of 3-ethyl-3-pentanol (Note 3) is added slowly but constantly by syringe (Note 4). At the end of addition the yellow tint of the butyllithium solution disappears. The alkoxide solution is standardized by hydrolysis of aliquots in water and by titration of the resulting lithium hydroxide with standard acid to a phenol-phthalein end point (Note 5). 

---