1,2-Bis(chlorodimethylsilyl)ethane1

[13528-93-3]  · C6H16Cl2Si2  · 1,2-Bis(chlorodimethylsilyl)ethane  · (MW 215.27)

(reagent for the protection of primary amines as their tetramethyldisilylazacyclopentane or Stabase adducts; used in combination with zinc to form organozinc carbenoids; electrophilic silylating reagent)

Physical Data: mp 36-41 °C; bp 198 °C/734 mmHg.

Form Supplied in: white, waxy solid with a sharp acid odor; 96% pure.

Handling, Storage, and Precautions: the dry solid reacts with moisture to produce hydrogen chloride. Incompatible with strong acids, alcohols, strong bases and strong oxidizers; may be ignited by static electricity; causes severe irritation to the respiratory tract. The reagent therefore should be used in a well ventilated hood.

Protection of Primary Amines.

Few protecting groups exist for the N,N-diprotection of primary amines (see 1,4-Bis(dimethylamino)-1,1,4,4-tetramethyldisilethylene). The tetramethyldisilylazacyclopentane or Stabase adduct (3) is particularly attractive for this purpose due to its ease of preparation, base stability and facile removal. This cyclic disilane is easily prepared (eq 1) from the commercially available title reagent (1).2 For primary amines with pKa values between 10 and 11, typical reaction conditions involve the treatment of a dichloromethane solution of the amine with (1) in the presence of two equivalents of triethylamine at room temperature. Subsequent workup with aqueous dihydrogen phosphate provides (3) in excellent yields.1 Stabase adducts are quite stable to strongly basic conditions such as n-Butyllithium and s-Butyllithium (at -25 °C), Lithium Diisopropylamide, and Grignard reagents making it a superb candidate for use in the alkylation of substrates bearing a primary amine. For example, protected amino acid derivatives are easily alkylated (eq 2).1,3 After formation of the lithium enolate of the protected ethyl glycinate (4) under standard conditions, exposure to various alkyl halides or aldehydes yields alkylation products such as (5).1

In addition to its base stability, this protecting group is readily cleaved under acidic conditions; often upon workup. After quenching the metallated dihydropyridine in eq 3 with the Stabase-protected aminoethyl disulfide (7), simple in situ treatment with saturated aqueous ammonium chloride liberates the regioisomeric free amines (8a) and (8b).4 However, more vigorous conditions are sometimes required. For example, allylic amine (11) was produced by exposure of the crude coupling product of (9) and (10) to an excess of ethanolic HCl at 0 °C (eq 4).5 Alternatively, Stabase deprotection can be achieved by reaction with ethanolic Sodium Borohydride, as demonstrated in eq 5. The tertiary alcohol resulting from Grignard addition to aromatic ketone (12) was thus deprotected by treatment with NaBH4 in ethanol to afford amino alcohol (13).6

Cleavage of Stabase adducts reveals a reactive primary amine that can be utilized in further transformations. Several groups have engineered one-pot, multistep processes that exploit both the protecting power and the acid lability of the cyclic disilane to generate amines in situ. An elegant example of such a transformation is illustrated in the general synthesis of 2-substituted pyrrolidines (17) which otherwise are difficult to synthesize (eq 6). Addition of the Stabase-protected Grignard (14) to an N-methoxy-N-methyl amide is followed by treatment of the reaction mixture with ethanolic HCl. Collapse of the intermediate hemiaminal is followed by Stabase cleavage and concomitant cyclization to the imine (16) in a single operation. The substituent R may vary from aliphatic to a wide variety of heterocyclic compounds.7

A further extension of this concept is shown in the 6-substituted 3-pyridinol synthesis described in eq 7. Treatment of condensation product (19) with 1 M HCl initiates Stabase deprotection that is followed by acid-catalyzed rearrangement of the resulting amino alcohol to pyridine (20).8

Formation of Organozinc Carbenoids.

When aromatic aldehydes and certain a,b-unsaturated carbonyl compounds are treated with zinc and 1,2-bis(chlorodimethylsilyl)ethane, an organozinc carbenoid results. This two-electron process is postulated to occur as depicted in eq 8. Sequential reaction of the two silicon atoms with the zinc carbonyl complex and subsequent extrusion of the cyclic siloxane (23) gives rise to the putative organozinc carbenoid (24). When generated in the presence of an alkene, cyclopropanes (25) are produced in good yields as in eq 9.9 When 2 equiv of carbonyl compound are employed, the organozinc carbenoid is trapped by excess carbonyl compound, and the intermediate epoxide is deoxygenated to yield products (26) of symmetrical dicarbonyl coupling (eq 10).10

Electrophilic Silylation Reagent.

1,2-Bis(chlorodimethylsilyl)ethane is not only an effective amine silylating reagent, but can also be employed in reactions with other anions. For example, when treated with the silver sulfonate salt as in eq 11, the nonafluorobutanesulfonic acid silyl ester (27), an extremely powerful silylating reagent, results.11 Carbanions are also effectively trapped by (1). A series of rigid butadiene Diels-Alder precursors such as (28) have been prepared in this fashion as outlined in eq 12.12

Related Reagents.

1,4-Bis(dimethylamino)-1,1,4,4-tetramethyldisilethylene.


1. Djuric, S.; Venit, J.; Magnus, P. TL 1981, 22, 1787.
2. Sakurai, H.; Tominaga, K.; Watanabe, T.; Kumada, M. TL 1966, 5493.
3. (a) Leduc, R.; Bernier, M.; Escher, E. HCA 1983, 66, 960. (b) Cavelier-Frontin, F.; Jacquier, R.; Paladino, J.; Verducci, J. T 1991, 47, 9807.
4. Poindexter, G. S.; Licause, J. F.; Dolan, P. L.; Foley, M. A.; Combs, C. M.; JOC 1993, 58, 3811.
5. Barger, T. M.; McCowan, J. R.; McCarthy, J. R.; Wagner, E. R. JOC 1987, 52, 678.
6. Gregory, W. A.; Brittelli, D. R.; Wang, C.-L. J.; Kezar, H. S. III; Carlson, R. K.; Park, C.-H.; Corless, P. F.; Miller, S. J.; Rajagopalan, P.; Wuonola, M. A.; McRipley, R. J.; Eberly, V. S.; Slee, A. M.; Forbes, M. JMC 1990, 33, 2569.
7. Basha, F. Z.; DeBernardis, J. F. TL 1984, 25, 5271.
8. Barrett, A. G. M.; Lebold, S. A. TL 1987, 28, 5791.
9. Motherwell, W. B.; Roberts, L. R. CC 1992, 21, 1582.
10. Afonso, C. A. M.; Motherwell, W. B.; O'Shea, D. M.; Roberts, L. R. TL 1992, 33, 3899.
11. Frasch, M.; Sundermeyer, W.; Waldi, J. CB 1992, 125, 1763.
12. Reich, H. J.; Reich, I. L.; Yelm, K. E.; Holladay, J. E.; Gschneidner, D. JACS 1993, 115, 6625.

Fatima Z. Basha & Steven W. Elmore

Abbott Laboratories, Abbott Park, IL, USA



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