(36e) Hybrid Chain-Growth/Step-Growth Mechanism Observed in Heterofunctional Thiol-Ene Polymerizations

Traditional
methods for polymer synthesis usually afford minimal control over the primary
sequence and solid-phase synthesis of sequence-controlled, biomimetic polymers
is limited by scalability. Utilizing thiol-X chemistries, first generating
sequence-controlled oligomers with the thiolate anion mediated thiol-Michael
reaction and then polymerizing with the orthogonal thiyl radical mediated
thiol-ene reaction, we have developed a method for producing sequence-ordered
periodic copolymers that are capable of diverse side-group customization, with
our primary focus being on attaching nucleobases and creating DNA-mimics. In
this talk, I will focus on the characteristics of heterofunctional thiol-ene
polymerizations in the context of synthesizing sequence-ordered polymers,
particularly, the effects of functional group chemistries on the reaction
kinetics and the monomer structure on molecular weight (MW) evolution.

            Despite the popularity
of thiol-ene coupling (TEC) chemistry in organic synthesis, in general, and
polymer chemistry, particularly, heterofunctional thiol-ene monomers (i.e. low MW
monomers containing both a thiol and an alkene functional group) have been
relatively unexplored, likely due to the inherent instability of thiol and ene functional
group chemistries when present in the same formulation. Initially, we investigated
the polymerizability and MW evolution of heterofunctional monomers containing
various side-group functionalities (e.g. alkyl chains, phenyl groups,
nucleobases) and the effect of varying the number of atoms separating the thiol
and ene functional groups. Surprisingly, while monitoring MW vs conversion,
we observed that high MW species emerged at low conversions (< 20%) when the
alkene and thiol are separated by 5 to 7 atoms, which is characteristic of a
chain-growth mechanism rather than the expected step-growth mechanism
associated with TEC reactions. Utilizing kinetics and MW profiles obtained by
real-time Fourier transform (rt-FTIR) spectroscopy and gel permeation
chromatography (GPC), respectively, it was determined that, due to the close
proximity of the two functional groups, upon generation of the 2° C-radical by
thiyl radical propagation into the alkene group, intramolecular chain-transfer
to the thiol dominates over intermolecular chain-transfer resulting in the
radical remaining on the same polymer chain and an apparent chain-growth/step-growth
hybrid mechanism. Although, the potential for high MW polymers in comparison to
the MWs achievable by traditional step-growth is desirable, the ease by which
these monomers cyclize results in significant reductions in polymer yield (up
to 50% monomer cyclization) leading us to develop strategies to eliminate
cyclization while maintaining the chain-growth evolution. Incorporation of the
monofunctional thiol, thiophenol, into the reaction mixture at an equivalency as
low as 1%, facilitates this goal as the low bond dissociation energy of
thiophenol’s S—H bond, compared to the monomer contained thiol, ensures that,
upon initiation, the radical population is partitioned exclusively into the
monofunctional thiol additive, thus preventing cyclization. Further, thiol-ene
reactions may be initiated without initiator by the direct photocleavage of the
S—H bond with ~254 nm light, but due to the extension of the thiophenol UV
absorption spectrum up to 330 nm, the thiophenol S—H bond may be selectively
cleaved in the presence of alkyl thiols so that thiophenol can be reacted
exclusively in the presence of alkyl thiols, which greatly increases the
ability to incorporate thiol-ene chemistries for performing one-pot, sequential
reactions.