Letter pubs.acs.org/OrgLett
Highly Stereoselective Oxazaborolidinium Ion Catalyzed Synthesis of (Z)‑Silyl Enol Ethers from Alkyl Aryl Ketones and Trimethylsilyldiazomethane Byung Chul Kang, Su Yong Shim, and Do Hyun Ryu* Department of Chemistry, Sungkyunkwan University, Suwon, 440-746, Korea S Supporting Information *
ABSTRACT: Highly stereoselective (Z)-silyl enol ethers were prepared from alkyl aryl ketones and trimethylsilyldiazomethane (TMSD) using an oxazaborolidinium ion catalyst. In addition, ring-expanded silyl enol ethers were successfully constructed from cyclic ketones. Their synthetic utilities were shown by sequential Mukaiyama aldol and [2 + 2]-cycloaddition reactions.
S
Lewis acid catalyzed stereoselective synthetic method for (Z)silyl enol ethers using alkyl aryl ketones and TMSD. Our initial studies to optimize reaction conditions were performed using acetophenone and TMSD in the presence of various Lewis acids (Table 1). These reactions were carried out at −40 °C using 20 mol % Lewis acids in CH2Cl2. Most Lewis acids tested afforded phenyl-migrated silyl enol ether 2a and methyl-migrated silyl enol ether 3a in 30 min. Tin triflate showed good catalytic activity generating the desired product 2a in 90% yield (Table 1, entry 4). However, the catalyst amount could not be reduced below 20 mol %, and a small amount of side product 3a was obtained. To overcome these limitations, the newly designed achiral oxazaborolidinium catalyst 1 was tested by changing the R group (Table 1, entries 7−12).6 We anticipated the bulkiness of the catalyst 1 would inhibit the binding of catalyst 1 to the silyl enol ether and selectively activate the alkyl aryl ketone.6 If the R group of catalyst 1 was an alkyl, such as methyl or isopropyl, protodesilylated benzyl methyl ketone was obtained (Table 1, entries 7 and 8). When the R group of catalyst 1 was an aryl, the desired (Z)-silyl enol ether 2a was generated as the major product. When the R group of catalyst 1 was changed to phenyl, the reaction was successfully catalyzed at −78 °C by 5 mol % of 1c to afford product 2a in 98% yield (Table 1, entry 10). Product configuration was confirmed by comparison with reported data3f and NOE analysis. With optimized reaction conditions for the catalytic (Z)-silyl enol ether formation reaction in hand, this methodology was evaluated with a range of aryl methyl ketones. Regardless of the aryl group electronic properties, reactions proceeded in a highly stereoselective manner, and the corresponding products were obtained in excellent yields (Table 2). To further investigate the substrate scope of the present catalytic system, the (Z)-silyl enol ether formation reaction was performed with a range of alkyl phenyl ketones and TMSD.
ilyl enol ethers are versatile intermediates in organic synthesis.1 Because the configuration of enol silane can affect the stereochemistry of subsequent events, many regioand stereodefined synthetic methods have been developed. Generally, stereoselective silyl enol ethers are synthesized through the enolate formation of carbonyl compounds and TMS (trimethyl silyl) trapping using TMSCl.2 Other methods include elimination of vinyl silyl compounds,3a Ru-catalyzed coupling reaction,3b Brook rearrangement,3c three-component reaction,3d and carbonyl addition of trimethylsilyldiazomethane (TMSD).3e−g Milder and more efficient methods are required, especially for acyclic ketone substrates. Our group recently reported Lewis acid-catalyzed carbonyl addition reactions of diazo compounds (Scheme 1, eq 1).4 Scheme 1. Lewis Acid Catalyzed Carbonyl Addition Reactions of Diazo Compounds
In the context of studies aimed at synthetic applications of TMSD, we anticipated that a similar type of TMSD addition with subsequent 1,2-alkyl or aryl migration would provide onecarbon elongated α-silyl ketones (Scheme 1, eq 2).5 However, instead of an α-silyl ketone, an unexpected (Z)-silyl enol ether was obtained. We were interested in the potential of this reaction and investigated suitable conditions for stereoselective synthetic methods. This report describes the first example of © 2014 American Chemical Society
Received: January 17, 2014 Published: March 26, 2014 2077
dx.doi.org/10.1021/ol500174q | Org. Lett. 2014, 16, 2077−2079
Organic Letters
Letter
Table 1. Lewis Acid Catalyzed (Z)-Silyl Enol Ether Formation Reactions with Acetophenone and TMSDa
entry
Lewis acid
2a, Z/Eb
2a, yieldc (%)
3a, yieldc (%)
1 2 3 4 5 6 7d 8e 9 10f 11 12
BF3·Et2O ZrCl4 Sc(OTf)3 Sn(OTf)2 Bi(OTf)3 EtAlCl2 1a 1b 1c 1c 1d 1e
>20 >20 >20 >20 >20 14
12 31 63 90 65 84
>20 >20 16 11
94 98 93 86
34 7 16 3 2 8
Highly Stereoselective Oxazaborolidinium Ion Catalyzed Synthesis of (Z)‑Silyl Enol Ethers from Alkyl Aryl Ketones and Trimethylsilyldiazomethane Byung Chul Kang, Su Yong Shim, and Do Hyun Ryu* Department of Chemistry, Sungkyunkwan University, Suwon, 440-746, Korea S Supporting Information *
ABSTRACT: Highly stereoselective (Z)-silyl enol ethers were prepared from alkyl aryl ketones and trimethylsilyldiazomethane (TMSD) using an oxazaborolidinium ion catalyst. In addition, ring-expanded silyl enol ethers were successfully constructed from cyclic ketones. Their synthetic utilities were shown by sequential Mukaiyama aldol and [2 + 2]-cycloaddition reactions.
S
Lewis acid catalyzed stereoselective synthetic method for (Z)silyl enol ethers using alkyl aryl ketones and TMSD. Our initial studies to optimize reaction conditions were performed using acetophenone and TMSD in the presence of various Lewis acids (Table 1). These reactions were carried out at −40 °C using 20 mol % Lewis acids in CH2Cl2. Most Lewis acids tested afforded phenyl-migrated silyl enol ether 2a and methyl-migrated silyl enol ether 3a in 30 min. Tin triflate showed good catalytic activity generating the desired product 2a in 90% yield (Table 1, entry 4). However, the catalyst amount could not be reduced below 20 mol %, and a small amount of side product 3a was obtained. To overcome these limitations, the newly designed achiral oxazaborolidinium catalyst 1 was tested by changing the R group (Table 1, entries 7−12).6 We anticipated the bulkiness of the catalyst 1 would inhibit the binding of catalyst 1 to the silyl enol ether and selectively activate the alkyl aryl ketone.6 If the R group of catalyst 1 was an alkyl, such as methyl or isopropyl, protodesilylated benzyl methyl ketone was obtained (Table 1, entries 7 and 8). When the R group of catalyst 1 was an aryl, the desired (Z)-silyl enol ether 2a was generated as the major product. When the R group of catalyst 1 was changed to phenyl, the reaction was successfully catalyzed at −78 °C by 5 mol % of 1c to afford product 2a in 98% yield (Table 1, entry 10). Product configuration was confirmed by comparison with reported data3f and NOE analysis. With optimized reaction conditions for the catalytic (Z)-silyl enol ether formation reaction in hand, this methodology was evaluated with a range of aryl methyl ketones. Regardless of the aryl group electronic properties, reactions proceeded in a highly stereoselective manner, and the corresponding products were obtained in excellent yields (Table 2). To further investigate the substrate scope of the present catalytic system, the (Z)-silyl enol ether formation reaction was performed with a range of alkyl phenyl ketones and TMSD.
ilyl enol ethers are versatile intermediates in organic synthesis.1 Because the configuration of enol silane can affect the stereochemistry of subsequent events, many regioand stereodefined synthetic methods have been developed. Generally, stereoselective silyl enol ethers are synthesized through the enolate formation of carbonyl compounds and TMS (trimethyl silyl) trapping using TMSCl.2 Other methods include elimination of vinyl silyl compounds,3a Ru-catalyzed coupling reaction,3b Brook rearrangement,3c three-component reaction,3d and carbonyl addition of trimethylsilyldiazomethane (TMSD).3e−g Milder and more efficient methods are required, especially for acyclic ketone substrates. Our group recently reported Lewis acid-catalyzed carbonyl addition reactions of diazo compounds (Scheme 1, eq 1).4 Scheme 1. Lewis Acid Catalyzed Carbonyl Addition Reactions of Diazo Compounds
In the context of studies aimed at synthetic applications of TMSD, we anticipated that a similar type of TMSD addition with subsequent 1,2-alkyl or aryl migration would provide onecarbon elongated α-silyl ketones (Scheme 1, eq 2).5 However, instead of an α-silyl ketone, an unexpected (Z)-silyl enol ether was obtained. We were interested in the potential of this reaction and investigated suitable conditions for stereoselective synthetic methods. This report describes the first example of © 2014 American Chemical Society
Received: January 17, 2014 Published: March 26, 2014 2077
dx.doi.org/10.1021/ol500174q | Org. Lett. 2014, 16, 2077−2079
Organic Letters
Letter
Table 1. Lewis Acid Catalyzed (Z)-Silyl Enol Ether Formation Reactions with Acetophenone and TMSDa
entry
Lewis acid
2a, Z/Eb
2a, yieldc (%)
3a, yieldc (%)
1 2 3 4 5 6 7d 8e 9 10f 11 12
BF3·Et2O ZrCl4 Sc(OTf)3 Sn(OTf)2 Bi(OTf)3 EtAlCl2 1a 1b 1c 1c 1d 1e
>20 >20 >20 >20 >20 14
12 31 63 90 65 84
>20 >20 16 11
94 98 93 86
34 7 16 3 2 8
