1-(N-Acylamino)alkyl Sulfones from N-Acyl-α-amino Acids or N-Alkylamides

Abstract

A variety of N-(1-methoxyalkyl)amides or carbamates react readily with sodium aryl sulfinates in the presence of triphenylphosphonium tetrafluoroborate or bromide in CHCl3 under mild conditions to give 1-(N-acylamino)alkyl sulfones in good yields. A combination of this reaction with the recently described electrochemical decarboxylative α-methoxylation of N-acyl-α-amino acids to give N-(1-methoxyalkyl)amides in the presence of 3-(1-piperidino)propyl-functionalized silica gel (SiO2-Pip) enables an effective two-pot transformation of N-acyl-α-amino acids to 1-(N-acylamino)alkyl sulfones. Alternatively, N-(1-methoxyalkyl)amides can be obtained by electrochemical α-methoxylation of either N-alkylamides, lactams, or N-alkylcarbamates.

Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance

“…126 These α -amidoalkylating agents can in turn be converted into amidosulfones which are commonly used surrogates for acyl iminiums. 127 N -[1-(Benzotriazol-1-yl)alkyl]amides may be obtained in a similar fashion. 128 …”

1-(N-Acylamino)alkyltriarylphosphonium Salts with Weakened Cα-P+ Bond Strength—Synthetic Applications

“…Applications of 1-( N -acylamino)alkyltriphenylphosphonium salts 4 (Ar = Ph) in the α-amidoalkylation of heteronucleophiles have been reported many times in the literature [5,6,7,8,10]. Usually in these types of reactions, it was necessary to use base catalysts, elevated temperature, and microwave irradiation.…”

“…N-[1-(p-Toluenesulfonyl)ethyl]pivalamide ( 10c ) [5]. Colorless crystals (124.7 mg, 88% yield), mp 143–145 °C.…”

“…The presence of a positively charged nucleofugal phosphonium moiety in the close surroundings of the N -acyl group determines its unique chemical properties such as high reactivity in α-amidoalkylations [1,2,3,4,5,6,7,8,9,10]. This type of reactions has enjoyed unflagging interest for years as a synthetic method with great potential, especially valuable for C-C and C-heteroatom bond formation [1,11,12,13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37].…”

“…In contrast, 1-( N -acylamino)alkyltriphenylphosphonium salts 1 (Z = Ph 3 P + X − ) do not require the use of acidic catalysts because of the permanent positive charge on the phosphonium group. However, the relatively high stability of C α -P + bond forces the use of a base catalyst (e.g., Hünig’s base, DBU, TBD; route b , Scheme 1 (I)) and sometimes microwave radiation [1,4,5,6,7,8,9,10]. …”