Dithiocarbamates have relatively fewer literature precedence demonstrating their chemical versatility compared to xanthates. Therefore, we performed several post- transformations on nicotinamide 4.33 to exemplify the utility of the dithiocarbamate as a synthetic intermediate. Reduction with deuterated hypophosphorous acid initiated by AIBN provided deuterated product 4.37 in good yield. Azide and allyl functionalities were similarly transferred in good yields using bis(tributyltin) and di-tert-butyl hyponitrite (DTBHN) initiation with the appropriate sulfone traps. While reduction of the dithiocarbamate was also possible with the more benign dilauroyl peroxide (DLP) to provide products 4.38 and 4.39, the complex
reaction mixtures that ensued complicated purification.
Figure 4.5. Dithiocarbamate post-functionalization reactions.
Thiol 4.40 was accessed using hydrazine hydrate to cleave the dithiocarbamate. Finally, under refluxing diphenyl ether (258 °C), elimination of the dithiocarbamate in a Chugaev-like mechanism afforded a mixture of olefins (4.41) in quantitative yield (Figure 4.6).70
Figure 4.6. Dehydrogenation via Chugaev-like elimination of dithiocarbamates.
4.5 Conclusion
A general approach to site‐specific, intramolecular C−H functionalization was made possible by the convergent synthesis of N‐dithiocarbamate amides from carboxylic acids and thiocarbamylsulfenamides. HLF-type reactivity of N‐dithiocarbamates derived from N- methylaniline was achieved using photo- and radical initiation, and was applicable to the diversification of both primary and secondary C−H sites in a number of complex natural products and drug derivatives. In particular, the successful functionalization of substrates containing electron-rich arenes, Lewis basic functionalities, and unsaturation, which would otherwise be problematic with other C–H functionalization methods, highlights the high functional group compatibility of the methodology. Overall, the products available via the intramolecular C–H dithiocarbamation offers opportunities for parallel functionalization and derivatization to other intermolecular C–H functionalization methods.
CHAPTER FIVE: CHEMO- AND REGIOSELECTIVE FUNCTIONALIZATION OF ISOTACTIC POLYPROPYLENE: A MECHANISTIC AND STRUCTURE-PROPERTY
STUDY 5.1 Introduction
Polyolefins make up a high-volume class of polymers. Their widespread use in packaging and coatings is in large part due to their desirable physical properties, including high tensile strength, low density, resistance to chemical degradation, and processability.71 Some of the most common polyolefins include polyethylene (PE) and polypropylene (PP), which are
semicrystalline materials that become pliable above their melting temperature (Tm) and solidify upon cooling. This property allows molding of the material into a variety of useful shapes. However, due to their inherent lack of functionality, polyolefins do not interface well with other materials, which limit their ability to form composites, adhesives, or blends.72 The ability to incorporate functionality into polyolefins, therefore, has the potential to generate new thermoplastics with unique properties for high-performance engineering applications. 5.2. Background
There are the two main approaches for accessing polar polyolefins: copolymerization and post-polymerization modification (PPM). In copolymerization, monomers containing
functionalities are used with α-olefins in the polymerization process, resulting in direct
incorporation of the desired functionality into the polymer from simple and often commercially- available monomers.73 However, these Lewis basic monomers poison the early transition-metal catalysts typically used in polyolefin polymerization processes, resulting in low molecular weight materials. Additionally, nonrandom incorporation of the polar comonomer is often
observed, resulting in materials with unevenly distributed polar functionalities. While significant advances have been made with the development of late transition-metals to minimize Lewis acid/base complex formation and reaction inhibition as pioneered by Brookhart with DuPont (Figure 5.1),74–76 the high costs associated with these specialized catalysts ultimately make them unviable for practical implementation.
Figure 5.1. Copolymerization to introduce functionalities to polyolefins.
Another strategy for accessing polar olefins involves the copolymerization of an α-olefin with a monomer containing a masked functionality that can be further manipulated to install the desired functionality in a second step (Figure 5.2).77 Certain monomers, including those containing borane, p-methylstyrene, and divinylbenzene, allow the copolymerization reaction to proceed without catalyst deactivation. However, the types of functionalities that can be incorporated into the final product are inherently limited with this approach.
On the other hand, post-polymerization modification (PPM) is a strategy for accessing new polymers from existing materials.3,72 The direct PPM of polyolefins via C–H
functionalization is particularly attractive for transforming inexpensive polyolefins already produced on industrial scale into functionalized materials. Ideally, PPM also enables modulation of functional group density in the polymer, which can be challenging with existing
copolymerization strategies. Significant macroscopic changes in the polymer’s physical
properties are observed with minor changes in the polymer’s chemical structure. Unlike for small molecules, the high stability of polyolefins allows the use of harsh and non-selective reagents.
Post-polymerization modification is practiced commercially with maleic anhydride grafting to polyethylene (PE) and isotactic polypropylene (iPP) by reactive extrusion, a process in which reactivity occurs in the melt phase at high temperatures inside an extruder.78 The thermal decomposition of a peroxide forms a radical species that can abstract a C–H bond, generating a carbon-centered radical (e.g. 5.1, Figure 5.3) that can add into maleic anhydride. With branched polyolefins, the C–H abstraction of weaker, tertiary C–H bonds is observed, resulting in tertiary carbon-centered radicals that are prone to β-scission processes. Chain scission events have deleterious effects on the properties of the polymer, resulting in low molecular weight species (5.3) with minimal incorporation of polar functionalities.79
A number of transition metal-catalyzed C–H functionalizations have been successfully applied on polymeric samples, most notably the rhodium-catalyzed hydroxylation of branched polyolefins by Hartwig and Hillmyer (Figure 5.4).80,81 The presence of trace metal, however, can catalyze auto-oxidation processes causing polymer degradation.82 Due to challenges associated with purification and fully eliminating metal from the product, strategies for post-polymerization modification that avoid the use of transition metals or Lewis acidic compounds are highly
desirable.
Figure 5.4. Rh-catalyzed C–H hydroxylation ofpolypropylene.
Relatively few strategies for metal-free PPM have been reported. In 2017, Liu and Bielawski reported the azidation of isotactic polypropylene (iPP) with an azidoiodinane reagent (Figure 5.5).83 Up to 3.5% azidation could be achieved, which occurred only at tertiary sites. As a result, the functionalized iPP showed a significant decrease in the average molar mass (Mn) of polymer chains, indicative of chain cleavage in the reaction, as well as a decrease in dispersity (Đ).
Also in 2017, Sun and Chen disclosed the C–H amination of polyethylene (Mn =7.9 kg/mol, Đ = 1.83) using NHPI as a C–H abstracting reagent and dialkyl azodicarboxylates as the radical trap (Figure 5.6).84Up to 15 mol % amination was observed using a di-tert-butyl
azodicarboxylate radical trap with no evidence of chain scission or coupling occurring under the reaction conditions. Unlike with unfunctionalized PE, blends could be obtained of the
functionalized PE with poly(methyl methacrylate) (PMMA).
Figure 5.6. C–H amination of polyethylene.
Recently, the C–H xanthylation was applied onto polyolefins in a collaboration between the Alexanian and Leibfarth groups (Figure 5.7).85 This initial report represented an important advancement in the field of PPM as a metal-free method with tunable degrees of
functionalizations available by adjusting the amount of xanthylamide 5.5 present in the system relative to repeat unit of the polymer. Importantly, due to the high methylene site-selectivity observed with xanthylamide, no chain scission was observed, and the versatility of the alkyl xanthate group enabled access to a diverse number of polyolefins containing useful
functionalities. The photoinitiation conditions used, however, was a limitation that we recognized would make practical large-scale implementation by reactive extrusion difficult. Therefore, we set out to develop thermal conditions to enable large-scale C–H xanthylations of branched polyolefins.
Figure 5.7. Photoinitiated C–H xanthylation of hyperbranched polyethylene.
5.3 Thermally-Initiated C–H Xanthylations