Benzylamines
Bn-NR2
T. W. Green, P. G. M. Wuts, Protective Groups in Organic
Synthesis,
Wiley-Interscience, New York, 1999, 579-580, 744-747.
Stability
| H2O: | pH < 1, 100°C | pH = 1, RT | pH = 4, RT | pH = 9, RT | pH = 12, RT | pH > 12, 100°C |
| Bases: | LDA | NEt3, Py | t-BuOK | Others: | DCC | SOCl2 |
| Nucleophiles: | RLi | RMgX | RCuLi | Enolates | NH3, RNH2 | NaOCH3 |
| Electrophiles: | RCOCl | RCHO | CH3I | Others: | :CCl2 | Bu3SnH |
| Reduction: | H2 / Ni | H2 / Rh | Zn / HCl | Na / NH3 | LiAlH4 | NaBH4 |
| Oxidation: | KMnO4 | OsO4 | CrO3 / Py | RCOOOH | I2, Br2, Cl2 | MnO2 / CH2Cl2 |
Protection
A highly active Mn(I) pincer catalyst enables an atom-economic and
highly efficient N-alkylation of amines with alcohols utilizing the borrowing
hydrogen methodology. A broad range of anilines and more challenging aliphatic
amines were alkylated with primary and secondary alcohols. The reaction offers
low catalyst loadings and mild reaction conditions.
L. Homberg, A. Roller, K. C. Hultzsch,
Org. Lett., 2019, 21, 3142-3147.
A simple Cu(I)-catalyzed C-N coupling of aliphatic halides with amines and
amides takes place readily at room temperature. The method uses CuBr, a common
and inexpensive atom transfer radical polymerization precatalyst, along with the
cheap ligand N,N,N',N'',N''-pentamethyldiethylenetriamine.
A. K. K. Fung, L.-J. Yu, M. S. Sherburn, M. L. Coote, J. Org. Chem., 2021, 86,
9723-3732.
N-Heterocyclic carbene-phosphine iridium complexes (NHC-Ir) are highly reactive
catalysts for N-monoalkylation of amides with alcohols via hydrogen transfer.
The reaction gave products in high isolated yields for a wide range of
substrates with low catalyst loading and in short reaction times.
S. Kerdphon, X. Quan, V. S. Parihar, P. G. Andersson, J. Org. Chem.,
2015,
80, 11529-11537.
K3PO4 mediates a mild sustainable protocol for the
coupling of primary alkyl chlorides and bromides with amides. The reaction does
not require strongly basic conditions, high temperatures, or the addition of an
organometallic catalyst, thereby enabling access to a remarkably orthogonal
scope of alkylated amide products in good yields.
J. P. Hibbard, J. G. Yam, E. B. Alsalek, A. Bahmonde, J. Org. Chem., 2022, 87,
12036-12040.
Other Syntheses of Benzyl-Protected Amino Groups
A highly efficient general
strategy for the synthesis of 2-amino acids by homologation of α-amino acids,
involving the Reformatsky reaction with a Mannich-type imminium electrophile is
reported.
R. Moumne, S. Lavielle, P. Karoyan, J. Org. Chem., 2006,
71, 3332-3334.
Deprotection
A chiral thiourea catalyzes the highly enantioselective hydrophosphonylation
of a wide range of N-benzyl imines. Subsequent deprotection by hydrogenolysis provides access to free α-amino
phosphonic acids in highly enantioenriched form.
G. D. Joly, E. N. Jacobson, J. Am. Chem. Soc.,
2004,
126, 4102-4103.
Formation of a bromo radical through the oxidation of bromide under mild
conditions enables an oxidative debenzylation of N-benzyl amides and O-benzyl
ethers to provide the corresponding amides and carbonyl compounds in high yields.
K. Moriyama, Y. Nakamura, H. Togo, Org. Lett., 2014,
16, 3812-3815.
Conversion of Benzyl-protected Amines to other functional groups
A visible-light-driven photoredox-catalyzed nonaqueous oxidative C-N cleavage
of N,N-dibenzylanilines provides 2° amides. The protocol also enables the conversion of 2-(dibenzylamino)benzamide to quinazolinones in the presence of
(NH4)2S2O8 as an additive.
N. Neerathilingam, M. B. Reddy, R. Anandhan, J. Org. Chem., 2021, 86,
15117-15127.
A highly efficient general
strategy for the synthesis of 2-amino acids by homologation of α-amino acids,
involving the Reformatsky reaction with a Mannich-type imminium electrophile is
reported.
R. Moumne, S. Lavielle, P. Karoyan, J. Org. Chem., 2006,
71, 3332-3334.
