Chemistry of a ketene-sulfur dioxide adduct. II. Reactions with heterocumulenes

Bohen, Joseph M.; Joullié, Madeleine M.

doi:10.1021/jo00955a017

“…Although the noncatalytic [2+2] cycloaddition reaction of ketenes with sulfur dioxide,18 sulfur diimides,2c or N ‐sulfinylanilines2a,b have been reported, we have not observed the noncatalytic background [2+2] cycloaddition reaction of ketenes and N ‐sulfinylaniline at −78 °C. Controlled experiments without the addition of ketenes revealed that no reaction of N ‐sulfinylaniline occurred in the presence of 10 mol % or 1 equivalent of 4 a′ at −78 °C 19.…”

Section: Methodscontrasting

confidence: 55%

N‐Heterocyclic Carbene Catalysis: Enantioselective Formal [2+2] Cycloaddition of Ketenes and N‐Sulfinylanilines

Jian¹,

He²,

Tang³

et al. 2011

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As analogues of both b-sultams and b-lactams, 3-oxo-bsultams (1,2-thiazetidin-3-one 1,1-dioxides), are a novel class of four-membered heterocycles showing interesting biological activities.[1] However, to the best of our knowledge, there is no report for the enantioselective synthesis of these heterocycles.[1a] We envisioned that the 3-oxo-b-sultams could be easily synthesized by oxidation of the corresponding 1,2-thiazetidin-3-one 1-oxides (A), [2] which could be accessed from the [2+2] cycloaddition of ketenes with N-sulfinylamines (Scheme 1).In addition, the cycloadduct A could also undergo a ring opening to give the a-mercapto acid derivatives and bmercapto amines, which are both key structures of bioactive compounds [3] and highly useful chiral reagents or ligands for asymmetric synthesis. [4] In the last several years, we successfully demonstrated that N-heterocyclic carbenes (NHCs) [5] are efficient catalysts for enantioselective reactions of ketenes, [6] including a series of formal [2+2], [3+2], and [4+2] cycloaddition reactions of ketenes with 2-oxoaldehydes, [7] activated ketones, [8] imines, [9] oxaziridines, [10] and heterodienes.[11] Herein we report an NHC-catalyzed enantioselective reaction of ketenes and Nsulfinylanilines to give chiral 1,2-thiazetidin-3-one 1-oxides.After some initial attempts, we were happy to find that ethyl(phenyl)ketene (1 a) and N-sulfinylaniline (2 a) reacted in the presence of 10 mol % of the NHC 4 a' [10a, 12] (generated from the triazolium salt 4 a derived from l-pyroglutamic acid in the presence of 20 mol % of Cs 2 CO 3 ) to give the corresponding 1,2-thiazetidin-3-one 1-oxide (3 aa) in 93 % yield with 96 % ee ( Table 1, entry 1). The NHC 4 b', having a free hydroxy group, also worked for the reaction but resulted in somewhat lower yield (entry 2). The NHC 5', [13] derived from aminoindanol, catalyzed the reaction to give the enantiomer of the cycloadduct in 95 % yield with 99 % ee (entry 3). No significant change in yield or enantioselectivity was observed when the catalyst loading was reduced to 5 mol % (entry 4). Although the yield decreased sharply to 36 %, the excellent enantioselectivity was maintained when 2 mol % of the NHC was utilized (entry 5). Solvent screening with toluene or THF resulted in a small increase of the yield (entries 6 and 7).A dramatic improvement in the yield was realized when 4 molecular sieves (M.S.) were added as the additive. The addition of M.S. may serve to remove trace amounts of water and thus reduce the hydrolysis of the ketene and N-sulfinylamine, thereby resulting in improvement of the yield of the cycloadduct. With the addition of M.S., both enantiomers of Scheme 1. Synthesis and applications of thiazetidinone oxide (A). Entry 4 or 5 (x mol %) [a] Solvent 3 aa Yield [%] [b] ee [%][c]

show abstract

“…Other N-sulfinylanilines, 2 b-2 e, having both electrondonating (4-Me, 4-MeOC 6 H 4 ) and electron-withdrawing groups (4-Cl, 4-FC 6 H 4 ) worked as well as N-sulfinylaniline 2 a (Table 2, entries [14][15][16][17]. In addition, the sulfinylanilines 2 f-2 h having 2-substituted aryl groups (2-MeO, 2-Cl, 2-FC 6 H 4 ) also worked very well, thus giving the cycloadducts in good yields with 91-99 % ee (entries [18][19][20].…”

mentioning

confidence: 99%

“…Although the noncatalytic [2+2] cycloaddition reaction of ketenes with sulfur dioxide, [18] sulfur diimides, [2c] or N-sulfinylanilines [2a,b] have been reported, we have not observed the noncatalytic background [2+2] cycloaddition reaction of ketenes and N-sulfinylaniline at À78 8C. Controlled experiments without the addition of ketenes revealed that no reaction of N-sulfinylaniline occurred in the presence of 10 mol % or 1 equivalent of 4 a' at À78 8C.…”

mentioning

confidence: 99%

N‐Heterocyclic Carbene Catalysis: Enantioselective Formal [2+2] Cycloaddition of Ketenes and N‐Sulfinylanilines

Jian

¹

,

He

²

,

Tang

³

et al. 2011

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As analogues of both b-sultams and b-lactams, 3-oxo-bsultams (1,2-thiazetidin-3-one 1,1-dioxides), are a novel class of four-membered heterocycles showing interesting biological activities.[1] However, to the best of our knowledge, there is no report for the enantioselective synthesis of these heterocycles.[1a] We envisioned that the 3-oxo-b-sultams could be easily synthesized by oxidation of the corresponding 1,2-thiazetidin-3-one 1-oxides (A), [2] which could be accessed from the [2+2] cycloaddition of ketenes with N-sulfinylamines (Scheme 1).In addition, the cycloadduct A could also undergo a ring opening to give the a-mercapto acid derivatives and bmercapto amines, which are both key structures of bioactive compounds [3] and highly useful chiral reagents or ligands for asymmetric synthesis. [4] In the last several years, we successfully demonstrated that N-heterocyclic carbenes (NHCs) [5] are efficient catalysts for enantioselective reactions of ketenes, [6] including a series of formal [2+2], [3+2], and [4+2] cycloaddition reactions of ketenes with 2-oxoaldehydes, [7] activated ketones, [8] imines, [9] oxaziridines, [10] and heterodienes.[11] Herein we report an NHC-catalyzed enantioselective reaction of ketenes and Nsulfinylanilines to give chiral 1,2-thiazetidin-3-one 1-oxides.After some initial attempts, we were happy to find that ethyl(phenyl)ketene (1 a) and N-sulfinylaniline (2 a) reacted in the presence of 10 mol % of the NHC 4 a' [10a, 12] (generated from the triazolium salt 4 a derived from l-pyroglutamic acid in the presence of 20 mol % of Cs 2 CO 3 ) to give the corresponding 1,2-thiazetidin-3-one 1-oxide (3 aa) in 93 % yield with 96 % ee ( Table 1, entry 1). The NHC 4 b', having a free hydroxy group, also worked for the reaction but resulted in somewhat lower yield (entry 2). The NHC 5', [13] derived from aminoindanol, catalyzed the reaction to give the enantiomer of the cycloadduct in 95 % yield with 99 % ee (entry 3). No significant change in yield or enantioselectivity was observed when the catalyst loading was reduced to 5 mol % (entry 4). Although the yield decreased sharply to 36 %, the excellent enantioselectivity was maintained when 2 mol % of the NHC was utilized (entry 5). Solvent screening with toluene or THF resulted in a small increase of the yield (entries 6 and 7).A dramatic improvement in the yield was realized when 4 molecular sieves (M.S.) were added as the additive. The addition of M.S. may serve to remove trace amounts of water and thus reduce the hydrolysis of the ketene and N-sulfinylamine, thereby resulting in improvement of the yield of the cycloadduct. With the addition of M.S., both enantiomers of Scheme 1. Synthesis and applications of thiazetidinone oxide (A). Entry 4 or 5 (x mol %) [a] Solvent 3 aa Yield [%] [b] ee [%][c]

show abstract

“…[53][54][55][56] Ketenes and ketimines have also been shown to react with liquid SO 2 in a pericyclic fashion to generate interesting sulfolene compounds. [57][58][59] Scheme 8 An early example of the hetero-Diels-Alder and cheletropic addition reactions involving SO 2…”

Section: Pericyclic Reactionsmentioning

confidence: 99%