DBU-Mediated Mild and Chemoselective Deprotection of Aryl Silyl Ethers and Tandem Biaryl Ether Formation

Abstract

An efficient method for the selective cleavage of aryl ­silyl ethers is established using 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). With either 1.0 or 0.10 equivalent of DBU, smooth de­silylation of various aryl silyl ethers was accomplished selectively in the presence of alkyl silyl ethers and other base-sensitive groups such as acetate and ester. In addition, direct transformation of aryl silyl ethers into biaryl ethers using a catalytic amount of DBU was possible through tandem desilylation and S_NAr reaction with ­activated aryl fluorides.

chemoselective - catalytic - desilylation - DBU - biaryl ether

References and Notes

1a Greene TW. Wuts PGM. Protective Groups in Organic Synthesis   3rd ed.:  Wiley and Sons; New York: 1999. 

1b Corey EJ. Venkateswarlu AJ. J. Am. Chem. Soc.  1972,  94:  6190 

For reviews, see:

2a Lalonde M. Chan TH. Synthesis  1985,  817 

2b Nelson TD. Crouch RD. Synthesis  1996,  1031 

2c Crouch RD. Tetrahedron  2004,  60:  5833 

Representative examples on selective deprotection of silyl ether:

3a Kishore Kumar GD. Baskaran SJ. J. Org. Chem.  2005,  70:  4520 

3b Sajiki H. Ikawa T. Hattori K. Hirota K. Chem. Commun.  2003,  654 

3c Ikawa T. Hattori K. Sajiki H. Hirota K. Tetrahedron  2004,  60:  6901 

3d Khan AT. Mondal E. Synlett  2003,  694 

3e Gopinath R. Patel BK. Org. Lett.  2000,  2:  4177 

4 Collington EW. Finch H. Smith IJ. Tetrahedron Lett.  1985,  26:  681 

5a Jiang Z.-Y. Wang Y.-G. Tetrahedron Lett.  2003,  44:  3859 

5b Ankala SV. Fenteany G. Tetrahedron Lett.  2002,  43:  4729 

5c Chakraborti AK. Sharma L. Sharma U. Tetrahedron  2001,  57:  9343 

5d Crouch RD. Stieff M. Frie JL. Cadwallader AB. Bevis DC. Tetrahedron Lett.  1999,  40:  3133 

5e Wilson NS. Keay BA. Tetrahedron Lett.  1997,  38:  187 

6 Oyama K.-I. Kondo T. Org. Lett.  2003,  5:  209 

7a Oediger H. Möller F. Eiter K. Synthesis  1972,  591 

7b Hermecz I. Advances in Heterocyclic Chemistry   Katrizky AR. Academic Press Inc.; New York: 1987.  Chap. 42. p.83 

8a Yeom C.-E. Kim YJ. Lee SY. Shin YJ. Kim BM. Tetrahedron  2005,  61:  12227 

8b Yeom C.-E. Lee SY. Kim YJ. Kim BM. Synlett  2005,  1527 

Known pK _{a ( DMSO)} values of the protonated Lewis bases: DABCO: 8.93, proton sponge: 7.50, TMG: 13.6, DBU: 12.0 (estimated value). For details, see:

9a

Bordwell pK _a Table (acidity in DMSO): http://chem.wisc.edu/areas/reich/pkatable (accessed July 2006).

9b

David Evans research group: http://daecr1.harvard.edu/pKa/pka.html (accessed July 2006).

10 This trend corresponds to the report on the susceptibility of silylated cresols to basic hydrolysis, which was examined using 5% NaOH in 95% MeOH: Davies JS. Higginbotham CL. Tremeer EJ. Brown C. Treadgold RC. J. Chem. Soc., Perkin. Trans. 1  1992,  3043 

11a Rao AV. Gurjar MK. Reddy KL. Rao AS. Chem. Rev.  1995,  92:  2135 

11b Nicolaou KC. Boddy CNC. J. Am. Chem. Soc.  2002,  124:  10451 

12 Cotter RJ. Engineering Plastics: A Handbook of Polyaryl Ethers   Gordon and Breach; Langhorne, PA: 1995. 

13

The nitro-substituted aryl fluorides were chosen as representative substrates, and we found that aromatic fluorides substituted with other electron-withdrawing groups, such as cyano or formyl, were also effective. The results will be described in a full account.

14

Cleavage of Aryl Silyl Ethers (Table 3, Entry 2); Typical Procedure: To a magnetically stirred solution of tert-butyldimethyl(2-naphthalenyloxy)silane (460 mg, 1.78 mmol) in anhyd MeCN (3.4 mL) and H₂O (0.18 mL) was added DBU (0.26 mL, 1.78 mmol). After the starting material disappeared (TLC), sat. aq NH₄Cl solution (5 mL) was poured into the reaction mixture. The mixture was extracted with CH₂Cl₂ (2 × 5 mL), and the organic layer was collected, dried over MgSO₄, filtered, and concentrated under reduced pressure. The resulting residue was purified further by passing through a short silica gel column (ca 5 cm) and after vacuum evaporation pure 2-naphthol was obtained (250 mg, 98% yield). Desilylated position of bissilyl ether was determined by the chemical shift difference of the free alcohol or alkyl substituents on silicon in NMR. Generally, the chemical shifts of aryl alcohols are higher than those of the aliphatic alcohols and alkyl substituent of aryl silyl ethers also exhibited more downfield signals in ¹H and ¹³C NMR than those of aliphatic ones.

15

Tandem, One-Pot Biaryl Ether Formation (Table 5, Entry 2); Typical Procedure: To a magnetically stirred solution of tert-butyldimethyl-(4-methoxyphenoxy)silane (410 mg, 1.73 mmol) in anhyd DMSO (3.5 mL) and H₂O (4 µL) were added p-fluoronitrobenzene (152 µL, 1.44 mmol), and DBU (13 µL, 0.173 mmol) sequentially at r.t. The mixture was heated to 80 °C, and the stirring was continued until the aryl fluoride disappeared on TLC. After completion of the reaction, the mixture was partitioned between Et₂O (5 mL) and brine (5 mL), and the organic layer was separated, dried over MgSO₄, filtered, and concentrated under reduced pressure. The residue was purified through silica gel column chromatography (n-hexane-EtOAc = 6:1) to afford the desired pure biaryl ether (320 mg, 91% yield).