Lewis Acid-catalyzed Reductive Etherification of Carbonyl Compounds with Alkoxyhydrosilanes [1]

Abstract

The TMSI-catalyzed reaction of aldehydes and ketones with alkoxydimethylsilanes gave unsymmetrical ethers in good to high yields. This reductive etherification is superior to the conventional method using two kinds of silicon reagents in terms of atom efficiency and ease of operation.

Key words

Lewis acids - reductive etherifications - ethers - aldehydes - bifunctional silicon reagents

1

Studies on Organosilicon Chemistry. No. 156.

References

• 2a Miura K. Hosomi H. In Lewis Acid Reagents   Yamamoto H. Oxford University Press; Oxford: 1999.  p.159 
• 2b Brewster JH. In Comprehensive Organic Synthesis   Vol. 8:  Trost BM. Fleming I. Pergamon Press; Oxford: 1991.  p.211 
• 3 Reductive etherification by catalytic hydrogenation in alcoholic acidic media: Verzele M. Acke M. Anteunis M. J. Chem. Soc.  1963,  5598 
• Reductive etherification with alcohols and hydrosilanes:
• 4a Doyle MP. DeBruyn DJ. Kooistra DA. J. Am. Chem. Soc.  1972,  94:  3659 
• 4b Loim NM. Parnes ZN. Vassilyeva SP. Kursanov DN. Zh. Org. Khim.  1972,  8:  896 
• 4c Nicolaou KC. Hwang C.-K. Nugiel DA. J. Am. Chem. Soc.  1989,  111:  4136 
• Reductive dimerization of carbonyl compounds with hydrosilanes:
• 5a Doyle MP. DeBruyn DJ. Donnelly SJ. Kooistra DA. Odubela AA. West CT. Zonnebelt SM. J. Org. Chem.  1974,  39:  2740 
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• 5c Sassaman MB. Prakash GKS. Olah GA. Tetrahedron  1988,  44:  3771 ; and ref.
• Lewis acid-catalyzed reductive etherification with alkoxysilanes and hydrosilanes (Lewis acid):
• 6a Kato J. Iwasawa N. Mukaiyama T. Chem. Lett.  1985,  743 ; (Ph₃CClO₄)
• 6b Sassaman MB. Kotian KD. Prakash GKS. Olah GA. J. Org. Chem.  1987,  52:  4314 ; (TMSI)
• 6c Hatakeyama S. Mori H. Kitano K. Yamada H. Nishizawa M. Tetrahedron Lett.  1994,  35:  4367 ; (TMSOTf)
• 6d Komatsu N. Ishida J. Suzuki H. Tetrahedron Lett.  1997,  38:  7219 ; (BiBr₃)
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• 9 Miura K. Ootsuka K. Suda S. Nishikori H. Hosomi A. Synlett  2001,  1617 

1

Studies on Organosilicon Chemistry. No. 156.

10

Alkoxydimethylsilanes 1 were prepared from alcohols, chlorodimethylsilane, and triethylamine (50-60% yield) or from alcohols and(diethylamino)dimethylsilane (50-70% yield).

11

For the formation of dibenzyl ether (reductive dimerization), see ref. [5c] and ref. [6b]

12

General Procedure for the TMSI-catalyzed Reductive Etherification (Method A): To a solution of 1 (1.10 mmol) and a carbonyl compound (1.00 mmol) in CH₂Cl₂ (1.0 mL) at 0 °C was added TMSI (1.0 M in CH₂Cl₂, 0.05 mL, 0.05 mmol). The mixture was stirred for 10 min and warmed to r.t. After a given reaction time, the reaction mixture was poured into water (20 mL) and extracted with t-BuOMe (3 × 10 mL). The combined organic layer was dried over Na₂SO₄ and evaporated. The residual oil was purified by silica gel column chromatography.