N-Boc ethyl oxamate: a new nitrogen nucleophile for use in Mitsunobu reactions

N-Boc ethyl oxamate can be directly coupled with primary and secondary alcohols under Mitsunobu conditions to afford various N-Boc amines after mild deprotection.     

N-Boc and N-CBz Ethyl Oxamates: New Gabriel Reagents

N-Boc and N-CBz ethyl oxamates can be directly coupled with various halides under Gabriel conditions which afford the corresponding N-protected amines after mild deprotection with LiOH.     

硅胶催化的选择性去除N-Boc保护基

发现了在回流的甲苯中, 以硅胶为催化剂, 多种N-Boc保护的伯胺、仲胺、氨基酸的氨基都可以迅速脱除Boc. 该方法具有条件温和、操作简便、反应时间短和产率高等优点. 同时, 其它常用的保护基Cbz和Fmoc等在同样的条件下不受影响.     

Reactivity series for s-BuLi/diamine-mediated lithiation of N-Boc pyrrolidine: applications in catalysis and lithiation of N-Boc piperidine

Using competition experiments between a range of ligands and (-)-sparteine, a reactivity series for N-Boc pyrrolidine lithiation using s-BuLi/diamines has been constructed; the results indicate that the s-BuLi/(+)-sparteine surrogate complex is more reactive than s-BuLi/(-)-sparteine and this has been exploited in the selection of ligand pairs for ligand exchange catalytic asymmetric lithiation of N-Boc pyrrolidine and lithiation of N-Boc piperidine.     

A facile direct anti-selective catalytic asymmetric Mannich reaction of aldehydes with preformed N-Boc and N-Cbz imines

Anti-selective Mannich reactions of N-Boc and N-Cbz protected imines with unmodified aldehydes proceeded smoothly under the catalysis of a secondary amine-thiourea catalyst, which led to high yields (70%-95%) and excellent enantioselectivity (up to 96 : 4 dr and >99% ee) under conventional organic synthetic operations.     

Highly enantioselective syntheses of anti homoaldol products by (-)-sparteine-mediated lithiation/transmetalation/substitution of N-Boc allylic amines

[reaction: see text](-)-Sparteine-mediated lithiation/transmetalation/substitution of N-Boc allylic amines provides anti-configured homoaldol precursors in yields of 38-85% and enantiomeric ratios of 83:17-99:1. Subsequent O-protection and hydrolysis allows access to O-protected homoaldol adducts in good yields. The absolute configurations of the homoaldol products have been assigned by calculation of optical rotations and by X-ray crystallography of derivatives. A stereochemical course of reaction for the lithiation/transmetalation/substitution sequence is proposed.     

Acid-Facilitated Debenzylation of N-Boc, N-Benzyl Double Protected 2-Aminopyridinomethylpyrrolidine Derivatives

2-Aminopyridinomethyl pyrrolidines represent a class of highly potent and selective neuronal nitric oxide synthase inhibitors. Conditions for a Mitsunobu reaction of a naphthol and a hindered secondary alcohol were optimized to give good to excellent yields. A key step in the synthesis of these inhibitors is the deprotection of the benzyl group from the N-Boc and N-Bn double protected 2-aminopyridine ring at a late stage of the synthesis, which has been proven difficult in our previous syntheses. Acetic acid was found to facilitate the N-Bn deprotection.     

Trans-selective asymmetric aziridination of diazoacetamides and N-Boc imines catalyzed by axially chiral dicarboxylic acid

Axially chiral dicarboxylic acid (R)-1d catalyzed reaction of diazoacetamides and N-Boc imines provided a novel organocatalytic means for the formation of enantiomerically enriched N-Boc protected trans aziridines.     

手性膦肽核酸单体的合成

肽核酸是一种潜在的反义和反基因药物。膦肽结构的引入克服了肽核酸低水溶性和低细胞膜通透性等缺点,有利于肽核酸的应用。本研究报道手性磷肽核酸单体的合成。还原氨化方法被用于实现N-Boc,N-Fmoc保护的丙氨醛与甘氨膦酸二酯的偶联,BBC-Cl,FEP等缩合剂被用于实现碱基侧链和母链的高效缩合。     

Ambient temperature zincation of N-Boc pyrrolidine and its solvent dependency

Sodium TMP-zincate, [(TMEDA)Na(TMP)((t)Bu)Zn((t)Bu)], can deproto-zincate N-Boc pyrrolidine at ambient temperature in hexane solution, whereas in toluene the captured α-carbanion of the heterocycle attacks the solvent setting off a cascade of reactions that ultimately produce a pyrrolidine-substituted enolate.     

Pd(0)-catalyzed cross-coupling reactions of boron derivatives with a lactam-derived N-Boc enol triflate

[formula: see text] The cross-coupling reaction of 2-(1-alkenyl)-1,3,2-benzodioxaboroles, obtained from alkynes and catecholborane, and other boron derivatives with a lactam-derived N-Boc enol triflate occurred under very mild conditions in a THF-water medium employing (Ph3P)2PdCl2 as a catalyst, providing the corresponding 6-substituted N-Boc 3,4-dihydro-2H-pyridines in high yields.     

Photochemical protection of amines with Cbz and Fmoc groups

The photochemical conversion of amines into carbamates was achieved using N-Cbz-, N-Fmoc-, and N-Boc-5,7-dinitroindolines. This reaction allows the protection of amines in neutral medium. Primary and unhindered secondary amines were protected to yield their benzyloxycarbonyl- and 9-fluorenylmethoxycarbonyl derivatives efficiently, whereas bulky amines or anilines gave low yields or no product. On the other hand, the formation of N-Boc compounds, although possible, proceeded only with low yields.     

Novel Practical Deprotection of N-Boc Compounds Using Fluorinated Alcohols

The thermolytic deprotection of N-Boc compounds was accomplished using TFE (2,2,2-trifluoroethanol) or HFIP (hexafluoroisopropanol) as solvents. Even though the cleavage of the t-butylcarbamate (Boc) group can be achieved at solvent reflux temperature, the deprotection process was significantly accelerated under microwave-assisted conditions. The practicality of this methodology was demonstrated on alkyl, aryl, and heteroaromatic N-Boc-amines.     

A new sparteine surrogate for asymmetric deprotonation of N-Boc pyrrolidine

The s-BuLi complex of a cyclohexane-derived diamine is as efficient as s-BuLi/(-)-sparteine for the asymmetric deprotonation of N-Boc pyrrolidine. This is the first example of high enantioselectivity using a non-sparteine-like diamine in such reactions. The (S,S)-diamine is a useful (+)-sparteine surrogate and was utilized in short syntheses of (-)-indolizidine 167B and an intermediate for the synthesis of the CCK antagonist (+)-RP 66803.     

Organocatalytic asymmetric Mannich reactions with N-Boc and N-Cbz protected alpha-amido sulfones (Boc: tert-butoxycarbonyl, Cbz: benzyloxycarbonyl)

Different malonates and beta-ketoesters can react with N-tert-butoxycarbonyl- (N-Boc) and N-benzyloxycarbonyl- (N-Cbz) protected alpha-amido sulfones in an organocatalytic asymmetric Mannich-type reaction. The reaction makes use of a simple and easily obtained phase-transfer catalyst and proceeds under very mild and user-friendly conditions. The optimised protocol avoids the preparation and the isolation of the relatively unstable N-Boc and N-Cbz imines that are generated in situ from the bench-stable alpha-amido sulfones. The corresponding Mannich bases are generally obtained in good yields and enantioselectivities, and can be readily transformed into key compounds, such as optically active beta3-amino acids in one easy step. Enantioenriched N-Boc and N-Cbz protected beta-amino acids that are suitable for peptide synthesis are also available from the Mannich adducts through simple manipulations. Control experiments showed the dual role of the enolate-catalyst ion pair in this reaction, as well as the crucial role of the presence of water to achieve high enantioselectivities.     

Preparation of N-Boc N-Alkyl Glycines for Peptoid Synthesis

A series of N-tert-butoxycarbonylated N-allyl, N-propargyl, N-benzyl or branched N-alkyl glycines, useful building blocks for the synthesis of N-alkyl glycine oligomers, have been prepared by N-alkylation of N-Boc glycine or by a two-step method: reductive alkylation and tert-butoxycarbonylation.     

New phenylselanyl group activation: synthesis of aziridines and oxazolidin-2-ones

After the study of different phenylselanyl group activators, halogenation by N-bromosuccinimide (NBS) has been shown to be the most suitable manner for cyclizing beta-phenylselanyl amines into aziridines and also enabled production of oxazolidin-2-ones from N-Boc beta-phenylselanyl amines in excellent yield.     

Asymmetric phase-transfer catalysts bearing multiple hydrogen-bonding donors: Synthesis and application in nitro-Mannich reaction of isatin-derived N-Boc ketimines

A series of bifunctional asymmetric phase-transfer catalysts bearing multiple hydrogen-bonding donors derived from cinchona alkaloids are synthesized, and successfully applied to asymmetric nitro-Mannich of isatin-derived N-Boc ketimines. The products 3-substituted 3-amino-oxindoles were constructed in excellent yields (96–99%) and good enantioselectivities (up to 95% ee).     

Oxaziridine-mediated amination of primary amines: scope and application to a one-pot pyrazole synthesis

Electrophilic amination of primary aliphatic and aromatic amines is reported using a diethylketomalonate-derived oxaziridine to afford the corresponding N-Boc hydrazines in good to excellent yields. The method allows a one-pot synthesis of pyrazoles from primary amines. [Reaction: see text]     

The highly enantioselective addition of indoles and pyrroles to isatins-derived N-Boc ketimines catalyzed by chiral phosphoric acids

The first asymmetric aza-Friedel-Crafts reaction of indoles and pyrroles with isatin-derived N-Boc ketimines catalyzed by chiral phosphoric acids is reported. In general, derivatives of substituted 3-amino-2-oxindoles were obtained with excellent enantioselectivities and high yields.