Convenient Access to α‐Amino‐ω‐Hydroxyl Heterobifunctional peg and ppo via a Sacrificial Hexahydro‐Triazine Star Strategy

DOI: 10.1002/marc.201900020

is mandatory. In this context we recently 

demonstrated a desymmetrization strategy 

for PEG, based on catalytic tosylation and 

HPLC separation.

[5]

 The second method 

relies on the direct initiation with a pro-

tected functional initiator and termination 

with a different functional group, which 

affords heterobifunctional PEG in high 

yields. Particularly PEG with a single pri-

mary amino end group is attractive, as it 

offers many selective reactions for biocon-

jugation. However, due to the high nucleo-

philicity of amines, the use of alkoxides 

bearing primary amines as an initiator in 

the AROP of ethylene oxide (EO) is not 

possible.

[6]

 Therefore, the amino group 

must be protected during the polymeriza-

tion. Using acetonitrile as an initiator for 

the AROP of EO followed by reduction 

with LiAlH

4

, 

α-amino  ω-hydroxyl PEG is 

obtained in a 90% purity.

[7]

 Another suitable protected amine 

initiator for the AROP is dibenzyl amino ethanol. The benzyl 

protective groups can be cleaved by catalytic hydrogenation 

after the polymerization.

[8]

 Silyl protected amines can also be 

used for the initiation of EO, which can release the primary 

amine in acidic media. However this leads to some extent to 

chain transfer reaction or broadened distributions.

[9]

 The use of 

an allylic alcohol as initiator with subsequent thiol-ene-click is 

another strategy to attach an amino terminus.

[10]

Aminal groups exhibit several similar characteristics as the 

acetal group and are stable under basic conditions, fulfilling 

the requirements of an AROP. Experimental and theoretical 

investigations into the stability of cyclic aminals in depend-

ence of the pH were carried out by Decker and coworkers.

[11]

 

In acidic media the aminal group hydrolyzes to an aldehyde 

and an amine.

[12,13]

 This renders the aminal functionality 

a useful protecting group for the access to primary amines 

without interfering in the AROP. Surprisingly, examples 

for the use of this group are scarce. Hirao et al. used a cyclic 

aminal protective group to protect the aldehyde functionality 

in 4-vinylbenzaldehyde during carbanionic polymerization. 

Subsequently, they released the aldehyde functionalities by 

acidic hydrolysis.

[14]

 Hexahydro-triazine consists of three linked 

aminal groups. This cyclic aminal is also formed in the syn-

thesis of acid-labile recyclable thermosets and epoxy resins.

[15,16]

 

To the best of our knowledge, use of the aminal functionality 

as a protecting group for amine functionalities during anionic 

polymerization has not been reported to date.