Practical asymmetric synthesis of α-branched 2-piperazinylbenzylamines by 1,2-additions of organometallic reagents to N-tert-butanesulfinyl imines

被引：40

作者：

Jiang, WL ^{[1
]}

Chen, C ^{[1
]}

Marinkovic, D ^{[1
]}

Tran, JA ^{[1
]}

Chen, CW ^{[1
]}

Arellano, LM ^{[1
]}

White, NS ^{[1
]}

Tucci, FC ^{[1
]}

机构：

[1] Neurocrine Biosci Inc, Dept Med Chem, San Diego, CA 92130 USA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 2005年 / 70卷 / 22期

关键词：

D O I：

10.1021/jo051514p

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

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.

引用

页码：8924 / 8931

页数：8

共 30 条

[1]

Alvaro G, 2002, SYNLETT, P651

[2] Additions of organometallic reagents to C=N bonds: Reactivity and selectivity [J].

Bloch, R .

CHEMICAL REVIEWS, 1998, 98 (04) :1407-1438

[3] Asymmetric synthesis of pre-protected α,α-disubstituted amino acids from tert-butanesulfinyl ketimines [J].

Borg, G ;

Chino, M ;

Ellman, JA .

TETRAHEDRON LETTERS, 2001, 42 (08) :1433-1436

[4] 4-{(2R)-[3-aminopropionylamido]-3-(2,4-dichlorophenyl)propionyl}-1-{2-[(2-thienyl)ethylaminomethyl]phenyl}piperazine as a potent and selective melanocortin-4 receptor antagonist-design, synthesis, and characterization [J].

Chen, C ;

Pontillo, J ;

Fleck, BA ;

Gao, YH ;

Wen, J ;

Tran, JA ;

Tucci, FC ;

Marinkovic, D ;

Foster, AC ;

Saunders, J .

JOURNAL OF MEDICINAL CHEMISTRY, 2004, 47 (27) :6821-6830

[5] Asymmetric synthesis of α,α-dibranched amines by the trimethylaluminum-mediated 1,2-addition of organolithiums to tert-butanesulfinyl ketimines [J].

Cogan, DA ;

Ellman, JA .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1999, 121 (01) :268-269

[6] Asymmetric synthesis of chiral amines by highly diastereoselective 1,2-additions of organometallic reagents to N-tert-butanesulfinyl imines [J].

Cogan, DA ;

Liu, GC ;

Ellman, J .

TETRAHEDRON, 1999, 55 (29) :8883-8904

[7] CHEMISTRY OF SULFUR-NITROGEN BOND .6. CONVENIENT ONE-STEP SYNTHESIS OF SULFENIMINES (S-ARYL THIOOXIMES) [J].

DAVIS, FA ;

SLEGEIR, WAR ;

EVANS, S ;

SCHWARTZ, A ;

GOFF, DL ;

PALMER, R .

JOURNAL OF ORGANIC CHEMISTRY, 1973, 38 (16) :2809-2813

[8] Asymmetric synthesis and properties of sulfinimines (thiooxime S-oxides) [J].

Davis, FA ;

Reddy, RE ;

Szewczyk, JM ;

Reddy, GV ;

Portonovo, PS ;

Zhang, HM ;

Fanelli, D ;

Reddy, RT ;

Zhou, P ;

Carroll, PJ .

JOURNAL OF ORGANIC CHEMISTRY, 1997, 62 (08) :2555-2563

[9] Concise asymmetric synthesis of α-amino acid derivatives from N-sulfinylimino esters [J].

Davis, FA ;

McCoull, W .

JOURNAL OF ORGANIC CHEMISTRY, 1999, 64 (10) :3396-3397

[10]

DAVIS FA, 1974, J AM CHEM SOC, V96, P5000, DOI 10.1021/ja00822a055

← 1 2 3 →