N-Sulfinyl Urea Research Articles

ChemInform Abstract: Highly Enantioselective Reduction of β‐Amino Nitroolefins with a Simple N‐Sulfinyl Urea as Bifunctional Catalyst.

Simple but effective: A structurally simple N-sulfinyl urea was found to be a highly efficient bifunctional catalyst, which allows for the development of a novel pathway for the construction of chiral β-amino nitroalkanes through enantioselective reduction of β-amino nitroolefins by trichlorosilane. High yields and excellent enantioselectivities were obtained for a broad range of β-arylamino nitroolefin substrates (see scheme).

N-Sulfinyl Urea as Bifunctional Catalyst: Hydrosilylation of β-Amino Nitroolefins

Key words bifunctional catalysis - N-sulfinyl ureas - hydrosilylation - β-amino nitroolefins

Highly Enantioselective Reduction of β‐Amino Nitroolefins with a Simple N‐Sulfinyl Urea as Bifunctional Catalyst

Simple but effective: A structurally simple N-sulfinyl urea was found to be a highly efficient bifunctional catalyst, which allows for the development of a novel pathway for the construction of chiral β-amino nitroalkanes through enantioselective reduction of β-amino nitroolefins by trichlorosilane. High yields and excellent enantioselectivities were obtained for a broad range of β-arylamino nitroolefin substrates (see scheme).

Catalytic Enantioselective Protonation of Nitronates Utilizing an Organocatalyst Chiral Only at Sulfur

The highly enantioselective protonation of nitronates formed upon the addition of α-substituted Meldrum's acids to terminally unsubstituted nitroalkenes is described. This work represents the first enantioselective catalytic addition of any type of nucleophile to this class of nitroalkenes. Moreover, for the successful implementation of this method, a new type of N-sulfinyl urea catalyst with chirality residing only at the sulfinyl group was developed, thereby enabling the incorporation of a diverse range of achiral diamine motifs. Finally, the Meldrum's acid addition products were readily converted to pharmaceutically relevant 3,5-disubstituted pyrrolidinones in high yield.

Enantio- and diastereoselective addition of thioacetic acid to nitroalkenes via N-sulfinyl urea catalysis

The enantioselective addition of thioacetic acid to nitroalkenes was achieved using N-sulfinyl urea catalysis. In this report, the scope of the reaction was extended to the enantio- and diastereoselective thioacetic acid addition to cyclic α,β-disubstituted nitroalkenes. Additionally, the role of the sulfinyl group was investigated by replacing it with a variety of aryl and sulfonyl groups. Of 15 urea catalysts synthesized and tested, none displayed comparable selectivity to the sulfinyl catalysts, highlighting the importance of the sulfinyl group in attaining high enantioselectivity in the thioacetic acid addition.

Enantio- and diastereoselective addition of cyclohexylMeldrum's acid to β- and α,β-disubstituted nitroalkenesvia N-sulfinyl urea catalysis

Using N-sulfinyl urea catalysis, a method has been developed for the asymmetric synthesis of biologically important γ-amino acids with a high level of efficiency, practicality and unprecedented control of multiple stereocenters. This method is based upon the highly enantio- and diastereoselective addition of cyclohexyl Meldrum's acid as an easily deprotectable monocarboxylic acid equivalent. The addition to both β-substituted and α,β-disubstituted nitroalkenes using N-sulfinyl urea organocatalyst 8 is described. The utility of this new method toward drug production is demonstrated by the mole scale preparation of a key precursor to the commercial drug Lyrica using catalyst 8 at only 0.2 mol% loading. Moreover, α,β-disubstituted nitroalkene addition products were efficiently converted to γ-amino acid derivatives without epimerization of either stereocenter.

Enantioselective Conjugate Addition of Thioacetic Acid to Nitroalkenes

N-Sulfinyl urea 1 was identified as powerful organocatalyst for the conjugate addition of thioacetic acid to nitroalkenes. In cyclopentyl methyl ether (CPME) the desired products were obtained in good yields (÷63%) and high enantio­selectivities (er up to 98:2). The reaction tolerates a wide range of substrates including electron-rich and electron-deficient aromatic, as well as linear and branched aliphatic nitroalkenes.

A Model Study on the Synthesis of the Marine Hepatotoxin Cylindrospermopsin

Model diene urea 7 has been converted to the corresponding N-sulfinyl urea 11, which undergoes stereoselective intramolecular hetero [4+2]-cycloaddition to afford dihydrothiazine oxide adduct 12. Treatment of 12 with PhMgBr, followed by stereospecific [2,3]-sigmatropic rearrangement, yields 14 which has the AB ring system and C-7,8 and 10 configuration of cyclindrospermopsin (1).