Diastereoselective synthesis of nitroso acetals from (S,E)-γ-aminated nitroalkenes via multicomponent [4 + 2]/[3 + 2] cycloadditions promoted by LiCl or LiClO₄

Abstract

SummaryChiral nonracemic aminated nitroso acetals were synthesized via diastereoselective multicomponent [4 + 2]/[3 + 2] cycloadditions employing new (S,E)-γ-nitrogenated nitroalkenes 5a–c as heterodienes, ethyl vinyl ether (EVE) as a dienophile, and selected electron-deficient alkenes as 1,3-dipolarophiles. The employment of different organic solutions of LiClO4 or LiCl as promoter systems provided the respective nitroso acetals with yields from 34–72% and good levels of diastereoselectivity. In addition, the nitroso acetal 9c was transformed to the pyrrolizidin-3-one derivative 14c, proving the usefulness of the route in the synthesis of an interesting chiral compound. The elucidation of the stereostructures was based on 2D COSY, NOESY and HSQC NMR experiments as well as an X-ray diffraction experiment.

Tandem Deoxygenation/Halogenation of N‐Oxides Under Acylation Conditions: Scope and In Situ IR Spectroscopic Study

“…The availability of these heterocyclic N ‐oxides together with their versatile reactivity make them useful intermediates in the synthesis of stereochemically complex molecules . Numerous total syntheses of natural alkaloids and pharmaceutically active molecules exploiting cyclic nitronates 1 have been developed by Denmark,[1d], our group, and other researchers …”

Synthesis of Steroidal D‐Ring‐Fused Pyrrolidines of Dehydroepiandrosterone

“…[17] The high-pressure-promoted multicomponent cycloadditions were carried out with enol ether 4, nitroalkene 25, and dipolarophiles with different functional groups (26)(27)(28)(29)(30). [18,19] The [4+2] and [3+2] cycloaddition reactions took place with complete regioselectivity [20] to give azonites 6-10 as mixtures of only two diastereoisomers (a and b), via azinate intermediates 31 (Scheme 3, Table 1). In most cases, only the major isomer (a) could be isolated in pure form.…”

Divergent and Diastereoselective Synthesis of α-Monosubstituted and trans-α,β-Disubstituted γ-Lactams from (S)-N,N-Dibenzyl-α-amino Aldehydes via Henry and Michael Reactions

“…Thus, the approach of the nucleophile malonate anion to the -nitro carbon was preferred by the less hindered Re-C face on the opposite side to the largest group following the Burgi-Dunitz trajectory. 53 In addition, the X ray diffraction analysis unequivocally established that the N,N-dibenzylated nitroalkenes 8a-c reacts in [4+2] cycloaddition 32 and Michael addition with exclusive anti-diastereoselectivity. 31 Thus, we could infer that the anti-diastereoisomers 10b,c were the unique diastereoisomers formed in the Michael addition between 8b,c and 9 (Table 2).…”

“…They are generally very easy to perform, are catalyzed by a large number of different basic homogeneous or heterogeneous systems and occur at room temperature in the presence of different organic solvents, water or without solvent. Based on our continued studies on the synthesis and use of new chiral nonracemic aliphatic nitro compounds in obtaining useful synthetic intermediates and natural products, [31][32][33][34][35][36][37][38][39] herein we describe a divergent and diastereoselective approach to obtain the -substituted -lactam 15 and trans-,-disubstituted -lactam 11 and several possible analogues, using the easily synthesized (S)-N,N-dibenzylated aldehydes 6a,b, as common precursors. Highly diastereoselective Michael additions, Henry reactions, and domino reduction--lactamization steps were successfully employed in these syntheses.…”

“…Next, to initiate the synthesis of the ,-disubstituted lactam 11 (Route 3 in Scheme 1) the chiral nitroalkenes 8b,c were prepared from N,N-dibenzylated aldehydes 6b,c in 94% and 86% global yield, respectively, via the route developed by us 31,32 (Table 2). It is worth mentioning that the nitroalkenes 8b,c are obtained in high chemical and enantiomeric purity and can be stored in a freezer or even at room temperature for several months without decomposition.…”