The Nitro-Mannich Reaction and Its Application to the Stereoselective Synthesis of 1,2-Diamines

Abstract

The addition of alkyl nitronate anions to PMB imines, derived from benzaldehyde or straight-chain carbaldehydes, in the presence of a Bronsted acid, proceeds in greater than 90% yield with up to 10:1 diastereoselection favoring the anti isomer. The mechanism of this addition reaction is intriguing and is under investigation. The moderately unstable β-nitro amines can be reduced with samarium diiodide and the PMB group removed with CAN, in good overall yields, to give sensitive 1,2-diamines without erosion of diastereoselectivity. This protocol represents a new, stereoselective synthesis of certain 1,2-diamines.

The Chemistry of Vicinal Diamines

“…The conversion of such a compound 444 (obtained from 443 together with amino hydroxylamine 445) into the corresponding diamine, characterized as the trans-imidazolidinone 446 (single diastereomer), was recently published [197b] (Scheme 110). The nitro ± Mannich reaction was employed as the key step in a stereoselective route to 1,2-diamines by Anderson et al [198] (Scheme 111). Deprotonation of the nitro compound 447 at À 78 8C, followed by addition of imine 448 and then of acetic acid, led to b-nitro amine 449.…”

Cu-catalyzed cross-dehydrogenative coupling: A versatile strategy for C–C bond formations via the oxidative activation of sp 3 C–H bonds

“…An efficient synthetic approach toward such compounds is through the nitro-Mannich (aza-Henry) reaction. The nucleophilic addition of nitroalkanes to imines generates ␤-nitroamine derivatives (31), which are readily converted into 1,2-diamines or ␣-amino carbonyl compounds by the reduction of the nitro group (32,33) or through the Nef reaction (34).…”

Catalytic One‐Pot Oxetane to Carbamate Conversions: Formal Synthesis of Drug Relevant Molecules

“…Thek ey hydroxycarbamate intermediate 20 (48% yield) was finally converted virtually quantitatively into Carisoprodol 21 by treatment with trichloroacetyl isocyanate. [36][37][38] Carbamate 24,o btained in 70% yield from oxetane 23 using asimilar catalytic carbamate formation as used for 20, was treated with ammonium cerium(IV)nitrate (CAN) to remove the 4-methoxybenzyl group (PMB) [39] and gavet he hemi-carbamate 25 of Felbatol in 95% yield.F or Carisoprodol, the original route [40] is based on stepwisec arbamation of 2-methyl-2-propyl-1,3-propanediol involving the use of phosgene or phosgene-derived dialkylcarbamater eagents.T hus, the newly developed protocolp rovides an alternative way of producing carbamate-derived pharmaceuticals using catalytic chemistry.…”