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Practical asymmetric synthesis of alpha-branched 2-piperazinylbenzylamines by 1,2-additions of organometallic reagents to N-tert-butanesulfinyl imines.
J Org Chem. 2005 Oct 28; 70(22):8924-31.JO

Abstract

[reaction: see text] 2-[4-(tert-Butoxycarbonyl)piperazinyl]benzylidene-tert-butanesulfinamides underwent nucleophilic 1,2-addition with different organometallic reagents to give highly diastereomerically enriched adducts. X-ray crystallography of the resulting alpha-branched N-Boc-2-piperazinylbenzyl-tert-butanesulfinamides confirms different mechanisms depending on the organometallic reagent used. Differential deprotection of the N-Boc and the tert-butanesulfinamides was investigated, and the dehydration byproducts have been identified and characterized. To avoid the formation of byproducts in the acidic deprotection step, the N-tert-butanesulfinamide group was converted to the corresponding N-tert-butanesulfonamide (Bus), which allowed for clean orthogonal deprotection. The efficient synthesis and deprotection of the N-Boc-2-piperazinylbenzyl-tert-butanesulfinamides herein described constitutes an attractive method for extensive structure-activity studies in the search for novel ligands of the human melanocortin 4 receptor.

Authors+Show Affiliations

Jiang W
Department of Medicinal Chemistry, Neurocrine Biosciences, Inc., San Diego, California 92130, USA.
Chen C
No affiliation info available
Marinkovic D
No affiliation info available
Tran JA
No affiliation info available
Chen CW
No affiliation info available
Arellano LM
No affiliation info available
White NS
No affiliation info available
Tucci FC
No affiliation info available

MeSH

AldehydesAlkylationBenzylaminesButanesCarbonCatalysisCrystallography, X-RayIminesLithiumMolecular StructureNitrogenStereoisomerismSulfur

Pub Type(s)

Journal Article

Language

eng

PubMed ID

16238329

Citation

Jiang, Wanlong, et al. "Practical Asymmetric Synthesis of Alpha-branched 2-piperazinylbenzylamines By 1,2-additions of Organometallic Reagents to N-tert-butanesulfinyl Imines." The Journal of Organic Chemistry, vol. 70, no. 22, 2005, pp. 8924-31.
Jiang W, Chen C, Marinkovic D, et al. Practical asymmetric synthesis of alpha-branched 2-piperazinylbenzylamines by 1,2-additions of organometallic reagents to N-tert-butanesulfinyl imines. J Org Chem. 2005;70(22):8924-31.
Jiang, W., Chen, C., Marinkovic, D., Tran, J. A., Chen, C. W., Arellano, L. M., White, N. S., & Tucci, F. C. (2005). Practical asymmetric synthesis of alpha-branched 2-piperazinylbenzylamines by 1,2-additions of organometallic reagents to N-tert-butanesulfinyl imines. The Journal of Organic Chemistry, 70(22), 8924-31.
Jiang W, et al. Practical Asymmetric Synthesis of Alpha-branched 2-piperazinylbenzylamines By 1,2-additions of Organometallic Reagents to N-tert-butanesulfinyl Imines. J Org Chem. 2005 Oct 28;70(22):8924-31. PubMed PMID: 16238329.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Practical asymmetric synthesis of alpha-branched 2-piperazinylbenzylamines by 1,2-additions of organometallic reagents to N-tert-butanesulfinyl imines. AU - Jiang,Wanlong, AU - Chen,Chen, AU - Marinkovic,Dragan, AU - Tran,Joe A, AU - Chen,Caroline W, AU - Arellano,L Melissa, AU - White,Nicole S, AU - Tucci,Fabio C, PY - 2005/10/22/pubmed PY - 2006/6/20/medline PY - 2005/10/22/entrez SP - 8924 EP - 31 JF - The Journal of organic chemistry JO - J Org Chem VL - 70 IS - 22 N2 - [reaction: see text] 2-[4-(tert-Butoxycarbonyl)piperazinyl]benzylidene-tert-butanesulfinamides underwent nucleophilic 1,2-addition with different organometallic reagents to give highly diastereomerically enriched adducts. X-ray crystallography of the resulting alpha-branched N-Boc-2-piperazinylbenzyl-tert-butanesulfinamides confirms different mechanisms depending on the organometallic reagent used. Differential deprotection of the N-Boc and the tert-butanesulfinamides was investigated, and the dehydration byproducts have been identified and characterized. To avoid the formation of byproducts in the acidic deprotection step, the N-tert-butanesulfinamide group was converted to the corresponding N-tert-butanesulfonamide (Bus), which allowed for clean orthogonal deprotection. The efficient synthesis and deprotection of the N-Boc-2-piperazinylbenzyl-tert-butanesulfinamides herein described constitutes an attractive method for extensive structure-activity studies in the search for novel ligands of the human melanocortin 4 receptor. SN - 0022-3263 UR - https://www.unboundmedicine.com/medline/citation/16238329/Practical_asymmetric_synthesis_of_alpha_branched_2_piperazinylbenzylamines_by_12_additions_of_organometallic_reagents_to_N_tert_butanesulfinyl_imines_ DB - PRIME DP - Unbound Medicine ER -