Lithium 1-(Dimethylamino)naphthalenide1

[74379-76-3]  · C12H13LiN  · Lithium 1-(Dimethylamino)naphthalenide  · (MW 178.20)

(reductive lithiations of thioacetals;2 generation of a-lithio ethers,3 a-lithio silanes;6 synthesis of a-trialkylsilyl ketones;7 generation of allyllithiums;1b desulfurization10)

Alternate Name: LDMAN.

Solubility: generated in THF

Preparative Methods: anhydrous THF and lithium metal ribbon are cooled to between -40 and -55 °C by use of a 1-hexanol/dry ice bath; 1-(dimethylamino)naphthalene is added slowly; the appearance of the dark green radical anion is evident within 10 min but complete conversion to LDMAN takes 3.5-4 h at -45 °C.

Handling, Storage, and Precautions: LDMAN must be prepared and stored below -45 °C. No method of titration has been developed.

Reductive Lithiation.

The major advantage of LDMAN for reductive lithiation over Lithium Naphthalenide is the ease in removal of the byproduct dimethylaminonaphthalene (DMAN) from the reaction mixture by extraction with dilute acid.2

Thioacetals.

Cyclopropane dithioacetals undergo reductive lithiation leading to cyclopropyllithium species which can be trapped by various electrophiles in high yields (eq 1).2 Ketene phenyl thioacetals can also be used under these conditions to yield vinyl substituted thioethers (eq 2).2

a-Lithio Ethers.

The generation of stabilized and unstabilized a-lithio ethers can be prepared and subsequently reacted with a variety of electrophiles (eq 3).3 Treatment of 1-methoxy-1-phenylthiocyclopropanes with LDMAN followed by 1,2-trapping with conjugated aldehydes or ketones yields 1-cyclopropylallyl alcohols. These alcohols rearrange to the corresponding 2-vinylcyclobutanones upon the addition of acid (eq 4).4 It was observed that Lithium 4,4-Di-t-butylbiphenylide (LDBB) was a better reagent for this transformation when the alkoxy cyclopropyl vinyl carbinols are acid sensitive.4b

The a-lithio derivatives of substituted tetrahydrofurans and tetrahydropyrans can be generated and reacted with aldehydes (eq 5).5 This approach led to the first stereoselective synthesis of (±)-trans-rosoxide. The organolithium derived for the tetrahydropyran was axial and could be equilibrated to the more stable equatorial species. A two-flask synthesis of brevicomin was performed with the a-lithio ether of a dihydropyran (eq 6).3

a-Lithio Silanes.

The use of a-lithio silanes is an excellent protocol for the Peterson alkenation.6 Diphenyl thioacetals are treated with LDMAN, Chlorotrimethylsilane, and LDMAN again, followed by trapping with an aldehyde or ketone leading to high yields of the b-silyl carbinol (eq 7). Elimination to the alkene can be accomplished with Potassium Hydride on the carbinol.6a An improved one-pot synthesis involves treatment of the lithium alkoxide with Potassium t-Butoxide.6b This route has led to the synthesis of a variety of synthetically versatile alkylidene- and allylidenecyclopropanes.6

a-Trialkylsilyl Ketones.

LDMAN cleaves selectively the weak C-Se bond of silyl enol ethers of a-phenylseleno ketones.7 The corresponding a-trialkylsilyl ketones were obtained in good yields after rearrangement of the trialkylsiloxyvinyllithium (eq 8). Modest yields were obtained for the acyclic analogs accompanied by the formation of alkynic compounds, which presumably arise via b-elimination of the siloxyvinyllithium species.

Allyllithiums.

The use of LDMAN provides a general route to the preparation of hydrocarbon allyl anions.1b The treatment of allylphenylthio ethers with LDMAN followed by reacting with Crotonaldehyde leads to a mixture of regioisomers (eq 9). A slight preference for attack at the more substituted allyl terminus was observed. Transmetalation of the allyllithium with TiIV leads selectively to the 1,2-addition product (derived from the more substituted terminus) as a 9:1 mix of diastereomers in high yield.

The regioselectivity of the allyl system can be reversed to favor the least substituted position by transmetalation with CeIII leading to cis- or trans-homoallylic alcohols (eq 10).8

Synthesis of the elusive (1,1,3,3-tetramethylallyl)lithium was accomplished via LDMAN reductive lithiation.9

Desulfurization.

LDMAN has been used to remove the phenylthio group of substituted cyclobutanones (eq 11).10 This method proved superior to Raney Nickel, which led to desulfurization and ketone reduction; lithium in ammonia led to an amide via ring cleavage.

Removal of the phenylthio group in 2-substituted 2-(phenylthio)cyclopropanecarboxamides led to high yields of the trans-substituted products (eq 12).11


1. (a) Cohen, T.; Bhupathy, M. ACR 1989, 22, 152. (b) Cohen, T.; Guo, B.-S. T 1986, 42, 2803. (c) Cohen, T.; Matz, J. R. Organomet. Synth. 1986, 3, 361.
2. Cohen, T.; Matz, J. R. SC 1980, 10, 311.
3. Cohen, T.; Matz, J. R. JACS 1980, 102, 6900.
4. (a) Cohen, T.; Matz, J. R. TL 1981, 22, 2455. (b) Cohen, T.; Brockunier, L. T 1989, 45, 2917.
5. Cohen, T.; Lin, M.-T. JACS 1984, 106, 1130.
6. (a) Cohen, T.; Sherbine, J. P.; Matz, J. R.; Hutchins, R. R.; McHenry, B. M.; Willey, P. R. JACS 1984, 106, 3245. (b) Cohen, T.; Jung, S.-H.; Romberger, M. L.; McCullough, D. W. TL 1988, 29, 25. (c) Brown, P. A.; Bonnert, R. V.; Jenkins, P. R.; Selim, M. R. TL 1987, 28, 693.
7. Kuwajima, I.; Takeda, R. TL 1981, 22, 2381.
8. (a) Guo, B.-S.; Doubleday, W.; Cohen, T. JACS 1987, 109, 4710. (b) McCullough, D. W.; Bhupathy, M.; Piccolino, E.; Cohen, T. T 1991, 47, 9727.
9. Cabral, J. A.; Cohen, T.; Doubleday, W. W.; Duchelle, E. F.; Fraenkel, G.; Guo, B.-S.; Yü, S. H. JOC 1992, 57, 3680.
10. Cohen, T.; Oulette, D.; Pushpananda, K.; Senaratne, A.; Yu, L. C. TL 1981, 22, 3377.
11. Tanaka, K.; Minami, K.; Funaki, I.; Suzuki, H. TL 1990, 31, 2727.

Mark D. Ferguson

Wayne State University, Detroit, MI, USA



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