Deprotection of a primary Boc group under basic conditions

Tom, Norma J.; Simon, Wendy M.; Frost, Heather N.; Ewing, Marcus

doi:10.1016/j.tetlet.2003.11.108

Cited by 59 publications

(39 citation statements)

References 3 publications

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“…These latter substrates undergo base-mediated elimination to provide isocyanates, which further react and/or decompose (Equation 13). 36 In general, the use of NaOt-Bu leads to increased amounts of products derived from substrate decomposition, whereas the use of Cs 2 CO 3 results in an increase in the generation of Heck arylation side products.…”

Section: Palladium-catalyzed Carboamination Reactions Of N-protected mentioning

confidence: 99%

Stereoselective Synthesis of Saturated Heterocycles via Palladium-Catalyzed Alkene Carboetherification and Carboamination Reactions

Wolfe¹

2008

Synlett

233

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The development of palladium-catalyzed carboetherification and carboamination reactions between aryl or alkenyl halides and alkenes bearing pendant heteroatoms is described. These transformations effect the stereoselective construction of useful heterocycles, such as tetrahydrofurans, pyrrolidines, imidazolidin-2-ones, isoxazolidines, and piperazines. The scope, limitations, and applications of these reactions are presented, and current stereochemical models are described. The mechanism of the product formation, which involves an unusual intramolecular syn-insertion of an alkene into a palladium-heteroatom bond, is also discussed in detail.

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Section: Palladium-catalyzed Carboamination Reactions Of N-protected mentioning

confidence: 99%

Stereoselective Synthesis of Saturated Heterocycles via Palladium-Catalyzed Alkene Carboetherification and Carboamination Reactions

Wolfe¹

2008

Synlett

233

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“…The use of t BuOLi instead of the Mo catalyst in the second step of the synthesis of carbamate 20a and/or PPh 3 , CBr 4 , and Et 3 N, for the generation of cyanate 18a resulted in almost the same chirality transfer, but somewhat lower yields. Carbamates 19 were hydrolyzed under basic conditions to give the free amines in excellent yields, with very good chirality transfer. Attempted carbamate cleavage with aqueous HCl or TFA (trifluoroacetic acid) in CH 2 Cl 2 , or by treatment with TMSI in CH 2 Cl 2 was unsuccessful, due to the formation of elimination products.…”

Section: Resultsmentioning

confidence: 99%

Rearrangement Reactions Leading to Optically Active α,α‐Disubstituted Primary Allylamines

2017

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Synthetic routes to α,α‐disubstituted allylamines have been examined. Racemic compounds were conveniently prepared by thermal Overman rearrangements of primary allylic alcohols with trisubstituted double bonds, but rearrangement of these substrates using the only commercially available compound known to catalyze enantioselective Overman rearrangements, the cobalt oxazoline palladacycle (R)‐COP‐Cl, failed. Instead, optically active secondary allylic alcohols with trisubstituted double bonds, obtained by Corey–Bakshi–Shibata reduction of the corresponding methyl ketones, were synthesized and converted into α,α‐disubstituted allylamines through a thermal Overman rearrangement or an allylic‐cyanate‐to‐isocyanate rearrangement. High chirality transfer (90–99 %) was obtained for both reaction sequences, but the yields were greatly improved when the allylic‐cyanate‐to‐isocyanate rearrangement was used.

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“…This was further confirmed by the fact that there were two distinctive singlets at 1.46 and 1.52 ppm (each integrating to nine protons) in the 1 H NMR spectrum (in CDCl 3 ) of the product. The instability of the Boc protecting group under strong basic conditions has been documented 5–6. Interestingly however, one broad singlet in the 1 H NMR spectrum was found from 2.30 to 2.40 ppm, indicating the presence of a hydroxyl group in the product.…”

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confidence: 85%

An alkoxide anion-triggered tert-butyloxycarbonyl group migration. Mechanism and application

Xue

Silverman

2010

Tetrahedron Letters

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We report a fast N→O tert-butyloxycarbonyl (Boc) migration of the imide (3R,4R)-tert-butyl 3-((6-(bis(tert-butoxycarbonyl)amino)-4-methylpyridin-2-yl)methyl)-4-hydroxypyrrolidine-1-carboxylate (2) via a base-generated alkoxide. The mechanism of the migration is intramolecular, involving an unusual nine-membered cyclic transition state. Keywords N to O migration; Boc group migration; intramolecular migration; crossover experimentIn the course of research on the development of chiral pyrrolidine-based inhibitors for neuronal nitric oxide synthase (nNOS), we evaluated various methods for the synthesis of compounds 1a and 1b, the key intermediates to prepare drug candidates for different kinds of neurodegenerative diseases. 1-3 Given the poor efficiency of benzyl deprotection during the reported synthetic route to 1a ,2 we attempted to use bis-Boc protection of the amino group on the pyridine ring (1b); these groups could be removed in one step during the late stage deprotection of the synthesis in excellent yields, providing a much more practical preparation of the final products on a multigram scale. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. To generate 1b, allylation of alcohol 2 was attempted by treating a solution of 2 in DMF with NaH (2 equiv) at room temperature, followed by the addition of allyl bromide (2 equiv). The reaction was quenched with H 2 O to form the product with 93% isolated yield (Scheme 1). To our surprise, mass spectrum and 1 H NMR data for this product did not match the anticipated product (1b). The isolated product has only an (M + H + ) peak at 448, which is 100 less than the calculated molecular weight of 1b, implying a possible lost of one Boc group from the desired product. This was further confirmed by the fact that there were two distinctive singlets at 1.46 and 1.52 ppm (each integrating to nine protons) in the 1 H NMR spectrum (in CDCl 3 ) of the product. The instability of the Boc protecting group under strong basic conditions has been documented. 5-6 Interestingly however, one broad singlet in the 1 H NMR spectrum was found from 2.30 to 2.40 ppm, indicating the presence of a hydroxyl group in the product. Further NOSEY NMR data showed that the allyl group was connected through the nitrogen atom of the amino functionality to the pyridine ring. 7 On the basis of these results, we assigned the product as (3R,4R)-tert-butyl 3-((6-(allyl(tertbutoxycarbonyl)amino)-4-methylpyridin-2-yl)methyl)-4-hydroxypyrrolidine-1-carboxylate (3). 8 It was also noted that: 1) compound 2 showed significant stability in aqueous NaOH even at accelera...

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Deprotection of a primary Boc group under basic conditions

Cited by 59 publications

References 3 publications

Stereoselective Synthesis of Saturated Heterocycles via Palladium-Catalyzed Alkene Carboetherification and Carboamination Reactions

Stereoselective Synthesis of Saturated Heterocycles via Palladium-Catalyzed Alkene Carboetherification and Carboamination Reactions

Rearrangement Reactions Leading to Optically Active α,α‐Disubstituted Primary Allylamines

An alkoxide anion-triggered tert-butyloxycarbonyl group migration. Mechanism and application

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