An Efficient Method for the Synthesis of Nitropiperidones

Abstract

A three step efficient strategy for the synthesis of substituted 5-nitropiperidones in high de, employing Michael addition of N-p-tolylsulfinyl beta-nitroamines to alpha,beta-unsaturated esters, hydrolysis of the sulfinyl group, and cyclization of the resulting free amines, has been developed. A very simple experimental procedure involving mild conditions and only one chromatographic purification are the main features of the process.

Abnormal Behaviour of Allenylsulfones under Lu’s Reaction Conditions: Synthesis of Enantiopure Polyfunctionalised Cyclopentenes

“…It is noteworthy that the stereocontrol (> 95 % diastereomeric excess (de)) observed in the hydrogenation of the bicyclic sulfones (+)-12 and 14 a-exo, with the sulfonyl group at C-5, is much higher than that obtained from analogous 4esters (64 % de). [12] This difference confirms that the position of the substituent in the bicyclic system (C-5 for sulfones and C-4 for esters) affects the stereoselectivity and increases the potential interest of adducts obtained from allenylsulfones.…”

“…Cycloaddition reactions: Initially we explored the reaction of racemic furanone (AE )-1 with p-tolylsulfonylallene (3) under the best conditions reported for Lus reaction of furanones with allenoates (catalytic amount of PPh 3 , benzene as the solvent and room temperature). [12] A mixture of (AE )-6 and 7 [22] and other unidentified products, presumably polymers derived from 3, were obtained. Compounds (AE )-6 and 7 were isolated and purified by column chromatography, with low isolated yield for compound (AE )-6 ( Table 1, entry 1).…”

“…The low endo selectivity observed in the reactions of 2 a with 5 contrasts with the exclusive formation of the endo adduct observed in the reactions of 2 a with allenoate. [12] In this case, we postulated that intermediate VI-A was favoured with respect to VI-B because the latter was destabilised by the Me/SOTol interaction (see Scheme 10). However, this situation would be identical for allenylsulfone 5 (V-B will be destabilised with respect to V-A by the Me/SOTol interaction), yet the endo-selectivity is very low.…”

“…Adducts obtained in these reactions bear an alkoxy carbonyl group at the C-4 position. [12] The mechanistic proposal is that usually accepted for Lus reaction, depicted in Scheme 1 [13] (in our reactions: X = H, SOTol (Tol = tolyl)).…”

Synthesis of Substituted α-Trifluoromethyl Piperidinic Derivatives

“…After a 1,4-addition of 94 to ethyl acrylate under basic conditions, the resulting aminoester 95 was treated with TFA to produce, after deprotection (NH 3 , MeOH), the trifluoromethyl-δ-lactam 96 (Scheme 30) [60]. …”