Boc₂O Selection Cannot Be Judged by Protection Installation Alone: Experimental Decision-Making from Substrate Nucleophilicity and Medium Effects to Deprotection Pathways

Introduction

The most common use of Boc₂O [di-tert-butyl dicarbonate] is to convert amines into Boc [tert-butyloxycarbonyl]-protected carbamates. In practical synthesis, however, deciding whether Boc₂O is appropriate cannot be based solely on whether the Boc group can be introduced smoothly at that step. Three aspects must be considered together: whether the nucleophilicity of the substrate nitrogen is sufficient to attack Boc₂O effectively, whether the reaction medium will significantly affect reaction performance, and whether the Boc group can later be removed under conditions acceptable for the overall route. Only when these three factors are considered together does Boc₂O become more than an isolated, commonly used protecting reagent; it becomes part of a complete amine protection-deprotection pathway.

1. Group Substrates by Reactivity First, Then Plan the Boc Installation Conditions

Boc installation depends first on the intrinsic reactivity of the nitrogen-containing substrate itself. For aliphatic amines and conventional amino acid derivatives, Boc protection can usually be carried out under established conditions. For aromatic amines, heteroaromatic amines, sulfonamides, and multifunctional amines, however, substrate reactivity, site selectivity, and the risk of side reactions must all be evaluated together. The study by Basel and Hassner on the Boc₂O/DMAP system showed that the outcomes of reactions of amines and alcohols in this system vary with substrate type, solvent polarity, DMAP loading, and reaction time. Therefore, one set of conditions should not be directly extrapolated to all nitrogen-containing substrates.

1.1 Judging the Difficulty of Boc Installation by Substrate Type

Substrate type	Reaction characteristics	Initial assessment	Experimental focus
Aliphatic amines, conventional amino acid derivatives	Nucleophilicity is usually good, and Boc installation is often straightforward	A standard mild set of conditions can be used as the starting point	Whether the reaction is clean, whether over-protection occurs, and whether workup is simple
Aromatic amines, heteroaromatic amines	Lower nucleophilicity; conversion is usually slower under standard conditions	Evaluate medium effects and activation/promoting strategies first rather than directly applying aliphatic amine conditions	Conversion, reaction time, and whether medium-assisted promotion is needed
Low-nucleophilicity nitrogen substrates such as sulfonamides	Reaction difficulty increases markedly	Treat the Boc route as one candidate option and optimize case by case	Whether the target N-Boc product is actually formed and whether starting material persists for a long time
Diamines or multifunctional substrates	Site competition and selectivity control are often involved simultaneously	Define the target protection site first, then design stoichiometry and addition sequence	Mono-/di-protection ratio, site selectivity, and local environment effects

2. The Reaction Medium Affects Both Boc Installation Efficiency and How the Conditions Should Be Set Up

When substrate nucleophilicity decreases, the effect of the medium on Boc installation must be evaluated separately. Chankeshwara and Chakraborti reported catalyst-free chemoselective N-Boc protection of various amine substrates in water at room temperature under acid-free and base-free conditions. Vilaivan reported that Boc protection of aromatic amines is markedly faster in alcoholic media than in aprotic media; NMR kinetic analysis showed that the reaction rate in CD₃OD is about 70 times that in CDCl₃. These findings show that the medium affects not only substrate solubility, but may also directly influence the rate, selectivity, and practical suitability of Boc installation.

2.1 Effects of Common Reaction Media and Promoting Conditions on Boc Installation

Condition type	Suitable situations	Possible role	Experimental focus
Aqueous or water-containing systems	Conventional amines; cases where milder conditions are preferred	Some amine substrates can undergo N-Boc installation under mild conditions, and workup is relatively straightforward in some systems	Weakly nucleophilic substrates, hydrophobic substrates, and multifunctional systems should be evaluated separately
Alcoholic media (such as methanol, ethanol)	Aromatic amines or amine systems with slow conversion	Can markedly accelerate Boc protection for some substrates	Medium effects are strongly substrate-dependent, so the results should not be directly generalized
Aprotic organic media	Conventional anhydrous conditions; cases where clear and controllable conditions are desired	Condition setup is relatively mature and reaction control is convenient	Not necessarily the preferred choice for more weakly nucleophilic substrates
Boc₂O/DMAP-promoted conditions	Cases requiring additional promotion or involving insufficient substrate reactivity	Can alter substrate reactivity and affect product distribution	Side reactions, off-pathway products, and pathway changes caused by condition variation must be monitored

3. Before Judging Whether Boc Is Suitable, Look First at the Subsequent Deprotection

Whether a Boc-based route is suitable depends first on whether the subsequent deprotection conditions are compatible with the overall synthetic sequence. Three points should be confirmed in advance: whether acid treatment is acceptable in later stages, whether other protecting groups and sensitive sites in the system can tolerate it, and whether tert-butyl-type protections such as tert-butyl esters or some tert-butyl ethers must be retained while N-Boc is removed. The protecting-group literature and related methodological studies show that the choice of Boc should be reasoned backward from the deprotection stage, rather than decided solely by whether the installation step proceeds smoothly.

Han, Tamaki, and Hruby reported that 4 mol/L hydrogen chloride in dioxane can be used for rapid removal of Nα-Boc from amino acid and peptide substrates. In the systems they examined, tert-butyl esters, some tert-butyl ethers, and tert-butyl thioethers could be retained, whereas phenolic tert-butyl ethers were not within this retention range. Accordingly, this condition is better suited to routes that require preferential removal of N-Boc while retaining certain tert-butyl-type protections as much as possible.

3.1 Experimental Assessment of Boc Deprotection Conditions

Deprotection condition	Suitability assessment	Main points of attention
Trifluoroacetic acid-based treatment	A common Boc deprotection route, suitable for systems with overall good acid tolerance	Whether the substrate is acid-stable and whether other protecting groups and sensitive sites can coexist under these conditions
4 mol/L hydrogen chloride in dioxane	Suitable for systems that require preferential removal of N-Boc while retaining tert-butyl esters or some tert-butyl ethers as much as possible	Whether the target substrate falls within the reported scope of selective applicability; particular care is needed to distinguish ordinary tert-butyl ethers from phenolic tert-butyl ethers
Stronger or more specialized acid systems	Used for specific substrates, specific synthetic systems, or special deprotection tasks	Substrate sensitivity, protecting-group combinations, operational safety, and scale-up feasibility

4. In Peptide Synthesis, Boc Deprotection and Final Cleavage Should Be Evaluated Separately

In peptide synthesis, the use of Boc must be considered at two distinct operational levels: first, removal of Nα-Boc [Nα-tert-butyloxycarbonyl] before and after each coupling cycle; second, removal of side-chain protecting groups and release of the peptide chain from the resin at the end of the synthesis. In the in situ neutralization protocol for Boc-chemistry solid-phase peptide synthesis reported by Schnölzer et al., 100% trifluoroacetic acid was used for rapid Boc removal. By contrast, the anhydrous hydrogen fluoride cleavage method reported by Jadhav et al. is used for final removal of side-chain protecting groups and release of the peptide from the resin.

In classical Boc/Bzl [Boc/benzyl] solid-phase peptide synthesis, the conditions are organized on the basis of graded acid sensitivity: Boc is responsible for the periodic protection and removal of the Nα-amino group, while benzyl-type side-chain protections and related resin linkages are removed together at the end under stronger acidic conditions. Albericio’s review places this division of protecting-group roles within the framework of orthogonal or graded protecting-group design in solid-phase peptide synthesis.

4.1 Key Decision Points for Boc Conditions in Different Synthetic Contexts

Scenario	Key decision point	Experimental focus
Small-molecule or solution-phase synthesis	Whether Boc facilitates subsequent step arrangement and deprotection	Whether installation proceeds smoothly, whether later stages can tolerate acid treatment, and whether it is compatible with other protecting groups
Boc-chemistry solid-phase peptide synthesis	Whether periodic Nα-Boc removal and final cleavage are clearly separated in function	Boc removal conditions and final side-chain deprotection/peptide cleavage conditions should be evaluated separately
Complex peptide sequences	The impact of acid treatment on sequence integrity and side reactions	Sensitive residues, scavenger selection, and final cleavage conditions should be considered together

5. Prioritize Boc₂O According to the Experimental Task

Whether Boc₂O should be prioritized depends on whether the current task meets three criteria at the same time: the substrate has acceptable reactivity, the conditions can provide controlled installation, and the downstream sequence allows acidic deprotection.

5.1 Prioritizing Boc₂O by Experimental Task

Current task	Priority assessment	Key decision point
Temporary amino protection of conventional aliphatic amines	Can be considered first	Installation conditions are usually well established; the main point is whether acid-sensitive sites are present in the system
Protection of aromatic amines or more weakly nucleophilic amines	Decide only after careful evaluation	First confirm whether the medium and promoting conditions are sufficient to support conversion
Selective monoprotection of diamines or multifunctional substrates	Can be considered	The focus is site selectivity rather than simply increasing reaction rate
Preferential removal of N-Boc while retaining tert-butyl esters or some tert-butyl ethers as much as possible	Worth focused evaluation	First confirm whether the target substrate is compatible with selective deprotection conditions
Later stages cannot tolerate acid treatment, or the system contains many acid-sensitive sites	Not a preferred choice	The cost of deprotection may outweigh the benefit of installation
Use of classical Boc-chemistry solid-phase peptide synthesis	Can be adopted	Periodic Boc removal and final cleavage must be organized separately

6. Product Navigation Table for Substrate Compatibility, Medium Selection, and Deprotection Assessment Around Boc₂O (Product Tables 1–4)

Research or experimental objective	Which table to consult first	Why this table	Which table to cross-reference	Navigation note
To decide first whether the Boc route itself is worth adopting, rather than assuming from the outset that the amine should simply be Boc-protected	Table 1	Table 1 centers on Boc₂O itself and the most common comparison protection routes such as Fmoc, Alloc, and Cbz. It is suitable for first deciding whether acid deprotection is more appropriate downstream, or whether it would be better to switch to a base-labile, hydrogenolytic, or palladium-catalyzed deprotection route	Then see Table 4	Clarifying in advance which type of deprotection pathway is intended downstream is usually more useful than looking only at whether protection is easy to install
To establish a basic set of Boc conditions for conventional aliphatic amines or other readily reactive amines	Table 2	Table 2 collects the most commonly used bases, catalysts, and reaction media for Boc protection. It is suitable for building a basic condition set first and then deciding whether stronger promotion or a solvent change is needed	Then see Table 3	For conventional substrates, the key is first to establish a clean, reproducible starting condition set with convenient workup
To handle more weakly nucleophilic nitrogen substrates such as aromatic amines and sulfonamides, and to understand why standard conditions are insufficient	Table 3	Table 3 isolates substrates such as aniline and p-toluenesulfonamide, which react more slowly and are more condition-sensitive, making it suitable for understanding the problem first at the level of substrate type	Then see Table 2	First confirm that the difficulty arises from reduced substrate nucleophilicity, then adjust the medium, base, and catalytic promotion conditions; this is more effective than blindly increasing loading in a standard recipe
To compare site selectivity in diamine, amino alcohol, and aminophenol systems rather than just asking whether a reaction occurs	Table 3	Table 3 focuses on model substrates such as ethylenediamine, ethanolamine, and o-aminophenol, which reveal mono-/di-protection or N/O competition, making it suitable for clarifying competitive relationships first	Then see Table 2	In such problems, the key is usually not conversion itself, but which site reacts first, whether over-protection occurs, and whether the medium and catalyst change the distribution
To compare systematically the effects of water, methanol, ethanol, THF, DCM, DMF, and related media on Boc protection performance	Table 2	Table 2 places media that can significantly alter Boc system behavior together with organic bases, making it suitable for side-by-side comparison of solvents and bases	Then see Table 3	Medium selection is best judged around specific substrates; the same solvent does not play the same role in ordinary aliphatic amine, aromatic amine, and amino alcohol systems
To study specifically what roles condition components such as DMAP, triethylamine, DIPEA, and N-methylmorpholine play in directing the system outcome	Table 2	Table 2 is suitable for comparing different roles such as “simple acid scavenger,” “acid scavenger plus catalytic promotion,” and “commonly used supporting base in peptide chemistry”	Then see Table 3	First distinguish whether these components are adjusting basicity, reaction rate, or potentially changing the reaction pathway; condition screening will then be more targeted
To judge whether Boc deprotection should prioritize TFA, HCl/dioxane, or a stronger cleavage system	Table 4	Table 4 centers on trifluoroacetic acid, hydrogen chloride/dioxane, anhydrous hydrogen fluoride, and common scavengers, making it suitable for establishing a decision framework for the deprotection and cleavage stage	Then see Table 1	The deprotection method often determines whether the protecting group is worth using upstream; if stronger acid treatment is undesirable downstream, Fmoc, Cbz, or Alloc routes should be compared as early as possible
To distinguish solution-phase Boc deprotection from the treatment mode used in Boc solid-phase peptide synthesis	Table 4	Table 4 helps first distinguish TFA-mediated N-Boc removal, final HF cleavage, and the role of scavengers under strongly acidic conditions	Then see Table 1	First separate the two steps of periodic Nα-Boc removal and final cleavage, then decide whether the current task belongs to solution-phase Boc deprotection or a Boc solid-phase peptide synthesis system
To build an overall understanding of the Boc-SPPS system and clarify the interplay among bases, media, and cleavage conditions	Table 4	Table 4 first clarifies the strong-acid cleavage and scavenger system, making the condition design logic of Boc-SPPS easier to understand	Then see Table 2	First distinguish the cleavage stage, then return to the roles of components such as DMF and N-methylmorpholine in solid-phase peptide synthesis for a clearer understanding

Table 1 | Core Boc Introduction Reagent and Orthogonal Comparison Protecting Groups

Category	CAS No.	Aladdin Cat. No.	Name	Grade or Purity	Product Features and Applications
Core Boc introduction reagent	24424-99-5	D106159	Di-tert-butyl dicarbonate	≥99%	The core reagent for N-Boc installation; suitable for establishing protection starting points for conventional amines, weakly nucleophilic amines, and multifunctional substrates, and can be evaluated together with downstream acid deprotection routes.
Base-labile amino protecting group introduction reagent	28920-43-6	F106534	Fmoc chloride	For HPLC derivatization, ≥99% (HPLC)	Used for Fmoc installation; suitable for orthogonal comparison with the Boc route to judge whether a base-labile deprotection pathway is more appropriate when the substrate or downstream steps are acid-sensitive.
Pd-removable amino protecting group introduction reagent	2937-50-0	A151782	Allyl Chloroformate	≥98%	Used for Alloc installation; suitable for providing a removal pathway distinct from Boc in multi-protecting-group systems, facilitating comparison of different downstream selective deprotection strategies.
Hydrogenolytically removable amino protecting group introduction reagent	501-53-1	B105737	Benzyl chloroformate	≥96%, contains 0.1% sodium carbonate as stabilizer	Used for Cbz installation; suitable for comparison with the acid deprotection route of Boc, helping determine whether hydrogenolysis is more appropriate than strongly acidic conditions for the target substrate.

Table 2 | Media, Acid-Scavenging Bases, and Catalytic/Promoting Components

Category	CAS No.	Aladdin Cat. No.	Name	Grade or Purity	Product Features and Applications
HCl/dioxane-type Boc deprotection reagent	7647-01-0	H399975	Hydrochloric acid solution	4 M in 1,4-dioxane	Corresponds to HCl/dioxane-type N-Boc deprotection conditions and is suitable for comparison with the TFA route; it can remove Nα-Boc relatively rapidly and, in some cases, retain tert-butyl esters, some tert-butyl ethers, and tert-butyl thioethers, but it is not suitable for phenolic tert-butyl ethers.
Alcoholic reaction medium	64-17-5	E111989	Ethanol	Guaranteed reagent, water ≤0.3%	Can be used as an alcoholic medium to examine changes in Boc protection rate and selectivity, especially in conjunction with condition screening for aromatic amines or more slowly reacting substrates.
Stronger inorganic base	1310-73-2	S111498	Sodium hydroxide	Guaranteed reagent, ≥96%	Suitable as a stronger basicity control to help assess substrate stability, selectivity, and side-reaction risk under more strongly basic conditions.
Common weak inorganic base	144-55-8	S112339	Sodium bicarbonate	Pharmaceutical grade, PharmPure™	A mild acid-scavenging base suitable as a starting condition for Boc protection of conventional amines and helpful for controlling overactivation and side reactions.
Common weak inorganic base	497-19-8	S432763	Sodium carbonate	Anhydrous, PharmPure™, JP, BP, Ph. Eur., NF	More basic than sodium bicarbonate; suitable as a condition control when stronger deprotonation is needed or when a more slowly reacting substrate must be pushed forward.
Aprotic ether reaction medium	109-99-9	T1491789	Tetrahydrofuran (THF)	Anhydrous, ≥99.9%, inhibitor-free, H2O ≤30 ppm	Commonly used in anhydrous Boc protection conditions; suitable for comparison with alcoholic or aqueous media when judging the effects of solvent polarity and proticity on conversion.
Common weak inorganic base	584-08-7	P485463	Potassium carbonate	Anhydrous, extra pure, reagent grade, ≥99%	Commonly used for acid scavenging and deprotonation in organic or biphasic systems; suitable for comparing the effects of different inorganic bases on conversion and selectivity.
Aprotic halogenated reaction medium	75-09-2	D433565	Dichloromethane	Anhydrous, ≥99.8%, stabilized with 40–150 ppm amylene	A classical anhydrous organic medium suitable for organizing Boc installation or dissolution/solvent-switch operations prior to acid deprotection under low-water conditions.
Alcoholic reaction medium	67-56-1	M140298	Methanol	Anhydrous, ≥99.8%, H2O ≤100 ppm	More strongly polar and protic; suitable for expanded comparison of the effects of alcoholic media on Boc protection rate, selectivity, and side reactions.
Supporting medium for HCl/dioxane-type deprotection	123-91-1	D431640	1,4-Dioxane	Anhydrous, ≥99.8%	The representative organic medium for HCl/dioxane-type Boc deprotection routes; suitable for comparison with TFA systems in terms of deprotection rate, selectivity, and substrate tolerance.
Polar aprotic reaction/elution medium	68-12-2	D119450	N,N-Dimethylformamide (DMF)	Anhydrous, ≥99.8%	Suitable for dissolution, washing/elution, and condition switching in polar substrates or peptide systems, and also useful for comparing organizational differences between Boc chemistry in homogeneous and solid-phase platforms.
Organic base and Lewis-basic medium	110-86-1	P111513	Pyridine	Anhydrous, ≥99.8%	Functions both as an acid scavenger and as a medium; suitable for organizing Boc installation under relatively mild conditions and for observing how a basic environment affects the reactivity of weakly nucleophilic substrates.
Common tertiary amine acid-scavenging base	121-44-8	T140677	Triethylamine	Anhydrous, ≥99.5%, Water ≤50 ppm	A classical organic base suitable for routine Boc installation and acid capture, often used as a baseline control condition.
Aqueous reaction medium	7732-18-5	W433890	Water	Suitable for inorganic trace analysis	Suitable for evaluating N-Boc protection under acid-free, base-free, or mildly basic conditions and for observing chemoselectivity among amine, alcohol, and phenol sites.
Hindered tertiary amine acid-scavenging base	7087-68-5	D109322	N,N-Diisopropylethylamine	Distilled grade, ≥99.5%	More sterically hindered and less nucleophilic; suitable as an organic base choice when participation of the base in side reactions needs to be minimized.
Common tertiary amine base in Boc-SPPS	109-02-4	M104643	N-Methyl morpholine	Distilled grade, ≥99.5%	Commonly used in Boc solid-phase peptide chemistry; suitable for comparing acid-scavenging and neutralization strategies in solution-phase and solid-phase platforms.
Acyl-transfer catalyst	1122-58-3	D109207	4-Dimethylaminopyridine	≥99%	Can alter the reaction behavior of Boc₂O toward amines, alcohols, and amino alcohol systems; suitable for promoting and mechanistic evaluation in weakly nucleophilic substrates or systems with difficult selectivity.

Table 3 | Model Substrates for Substrate Nucleophilicity and Chemoselectivity

Category	CAS No.	Aladdin Cat. No.	Name	Grade or Purity	Product Features and Applications
Diamine selectivity model substrate	107-15-3	E431349	Ethylenediamine	Suitable for synthesis	Suitable for examining the effects of stoichiometry, addition sequence, and local environment on the distribution of mono-protection versus di-protection.
Amino alcohol competition model substrate	141-43-5	E103808	Ethanolamine	Distilled grade, ≥99.5%	Contains both an amine and an alcohol; suitable for observing N/O selectivity as well as the effects of medium, base, and DMAP on the reaction pathway.
Aromatic amine model substrate	62-53-3	A112119	Aniline	Standard for GC, ≥99.9% (GC)	Less nucleophilic than ordinary aliphatic amines; suitable for observing how alcoholic media, DMAP, or more appropriate base systems improve Boc installation efficiency.
Hindered aliphatic amine model substrate	108-91-8	C105033	Cyclohexylamine	Moligand™, Standard for GC, ≥99.5% (GC)	Combines reasonably good nucleophilicity with a certain degree of steric hindrance; suitable for comparing the effects of steric hindrance on the rate of Boc installation and condition requirements.
Low-nucleophilicity nitrogen substrate model	70-55-3	T102875	p-Toluenesulfonamide	GR, ≥99%	Can be used to evaluate the activation difficulty and promoter dependence of weaker nucleophilic nitrogen substrates under Boc conditions.
Conventional aliphatic amine model substrate	100-46-9	B108477	Benzylamine	AR, ≥99%	Represents a more nucleophilic primary amine; suitable for establishing a baseline for Boc installation conversion and workup.
Aminophenol competition model substrate	95-55-6	A104089	o-Aminophenol	≥99%	Contains both an amine and a phenolic hydroxyl group; suitable for evaluating N/O selectivity, cyclization side reactions, and medium effects in aromatic systems.

Table 4 | Boc Deprotection, Strong-Acid Cleavage, and Scavenger Components

Category	CAS No.	Aladdin Cat. No.	Name	Grade or Purity	Product Features and Applications
Reference material for strong-acid conditions related to HF cleavage	7664-39-3	H116232	Hydrofluoric acid	Guaranteed reagent, ≥40%	Can be used to understand the HF cleavage route in Boc/Bzl solid-phase peptide synthesis and its division of labor relative to periodic Boc removal; this product is an aqueous hydrofluoric acid solution and should not be interpreted directly as the classical final cleavage conditions using anhydrous HF.
Aromatic ether-type scavenger	100-66-3	A103684	Anisole	Anhydrous, ≥99.7%	Commonly used in strong-acid cleavage systems to trap highly reactive intermediates and help reduce side reactions in aromatic or sulfur-containing substrates.
Classical Boc deprotection acid	76-05-1	T433655	Trifluoroacetic acid (TFA)	Anhydrous, ≥99%	One of the most common acids for Boc removal in solution-phase and peptide chemistry; suitable for establishing benchmark conditions for rapid acid deprotection.
Thioether-type scavenger	75-18-3	M119696	Methyl sulfide (DMS)	Anhydrous, ≥99%	Can assist in scavenging reactive species that may trigger side reactions such as alkylation in strong-acid cleavage systems; suitable for combined use with other scavengers.
Phenolic scavenger	106-44-5	C108250	p-Cresol	Standard for GC, ≥99.7% (GC)	Can serve as a scavenger in acid cleavage systems and also helps suppress certain side reactions associated with aromatic side chains.
Thioether-type scavenger	100-68-5	T107511	Methyl phenyl sulfide	≥99%	Commonly used in TFA or HF cleavage systems; suitable for improving protection of sensitive peptide segments or substrates prone to side reactions.
Silane-type hydride-donor scavenger	6485-79-6	T420182	Triisopropylsilane (TIPS)	≥98.5%	Commonly used together with TFA to quench reactive intermediates generated during acid cleavage, helping improve deprotection cleanliness in the presence of sensitive residues.
Aromatic thiol scavenger	106-45-6	T109389	p-Thiocresol	≥98%	Suitable for providing stronger trapping ability under harsher cleavage conditions and commonly used to control side reactions in systems containing sensitive sulfur or aromatic sites.
Dithiol scavenger	540-63-6	E106222	1,2-Ethanedithiol	≥97%	Particularly effective in protecting sensitive substrates containing sulfur or substrates prone to alkylation, and commonly used to suppress side reactions during strong-acid deprotection of peptides.

Note: The above are representative Aladdin products. For more product specifications, please refer to the product list at the end of the article, or search the Aladdin website using the “product name/CAS/catalog number.”

References

[1] Basel Y, Hassner A. Di-tert-butyl dicarbonate and 4-(dimethylamino)pyridine revisited: Their reactions with amines and alcohols. J Org Chem. 2000;65(20):6368-6380. doi:10.1021/jo000257f.

[2] Chankeshwara SV, Chakraborti AK. Catalyst-free chemoselective N-tert-butyloxycarbonylation of amines in water. Org Lett. 2006;8(15):3259-3262. doi:10.1021/ol0611191.

[3] Vilaivan T. A rate enhancement of tert-butoxycarbonylation of aromatic amines with Boc2O in alcoholic solvents. Tetrahedron Lett. 2006;47(38):6739-6742. doi:10.1016/j.tetlet.2006.07.097.

[4] Han G, Tamaki M, Hruby VJ. Fast, efficient and selective deprotection of the tert-butoxycarbonyl (Boc) group using HCl/dioxane (4 M). J Pept Res. 2001;58(4):338-341. doi:10.1034/j.1399-3011.2001.00935.x.

[5] Schnölzer M, Alewood P, Jones A, Alewood D, Kent SBH. In situ neutralization in Boc-chemistry solid phase peptide synthesis: Rapid, high yield assembly of difficult sequences. Int J Pept Res Ther. 2007;13:31-44. doi:10.1007/s10989-006-9059-7.

[6] Albericio F. Orthogonal protecting groups for Nα-amino and C-terminal carboxyl functions in solid-phase peptide synthesis. Biopolymers. 2000;55(2):123-139. doi:10.1002/1097-0282(2000)55:2<123::AID-BIP30>3.0.CO;2-F.

[7] Wuts PGM. Greene’s Protective Groups in Organic Synthesis. 5th ed. Hoboken, NJ: Wiley; 2014.

[8] Kocieński PJ. Protecting Groups. 3rd ed. Stuttgart: Thieme; 2005.

[9] Jadhav KB, Woolcock KJ, Muttenthaler M. Anhydrous Hydrogen Fluoride Cleavage in Boc Solid Phase Peptide Synthesis. In: Hussein WM, Skwarczynski M, Toth I, eds. Peptide Synthesis: Methods and Protocols. Methods in Molecular Biology. Vol 2103. New York, NY: Humana; 2020:41-57. doi:10.1007/978-1-0716-0227-0_4.

For more related articles, see below:

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The Methodological Value of Boc-Oxyma: Low-Racemization Coupling, Route Continuity, and Extended Applications

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