Science of Synthesis

Liu, J.; Johnson, J. A., Science of Synthesis: N-Heterocyclic Carbenes in Catalytic Organic Synthesis, (2016) 2, 102.

‌Table 1‌ compares results obtained for ring-opening metathesis polymerization (ROMP) of several monomers using complexes ‌3‌, ‌4‌, and ‌5‌, and ‌Scheme 5‌ shows a representative ROMP reaction of exo,exo-5,6-bis[(benzyloxy)methyl]bicyclo[2.2.1]hept-2-ene to give polymer ‌8‌. This data shows that in most cases catalyst ‌5‌ is the optimal choice for achieving low dispersity values (Ð) and high monomer conversions. Furthermore, the success of ROMP critically depends on solvent choice; key considerations include initiator and monomer solubility as well as the solubility of the growing polymer. Ruthenium complexes ‌3‌–‌6‌ are effective in organic solvents such as dichloromethane, tetrahydrofuran, and toluene. Catalysts ‌3‌, ‌4‌, and ‌5‌ have been used for ROMP in dimethylformamide and protic solvents for the polymerization of polar monomers, such as peptides.[‌24‌–‌29‌] Temperature and monomer concentration also play important roles in ROMP. High monomer concentrations ensure that the rate of propagation is large relative to any potential termination or undesired chain-transfer reaction. For example, sub-optimal concentrations can lead to secondary metathesis reactions, such as intermolecular and intramolecular chain-transfer (“backbiting”). These side reactions can lead to cyclic oligomers, particularly in cases of polymers with flexible backbones.[‌4‌] With regard to reaction temperature, a “ceiling temperature” exists for a given concentration of monomer at which the entropic penalty of polymerization is larger than the enthalpic gain from ring opening.[‌30‌] In general, higher monomer concentrations and lower temperatures are preferred for ROMP. The most popular cyclic alkene for ROMP is norbornene and its derivatives.[‌4‌,‌5‌] A large variety of functional groups have been shown to be compatible with ROMP using complexes ‌5‌ and ‌6‌, including esters, alcohols, carboxylic acids, aldehydes, ketals, and quaternary amine salts. ROMP has also been used to polymerize biomolecules without the need for tedious protection and deprotection chemistries or purification methods. Examples exist in the literature for ROMP of alkene-conjugated peptides, including non-protected amino acids,[‌26‌–‌29‌,‌31‌–‌33‌] nucleobases,[‌34‌–‌38‌] and sugars.[‌39‌–‌43‌] At high degrees of polymerization, unprotected cysteine, lysine, and arginine are the most problematic with ROMP.[‌26‌] ROMP of these polar molecules can potentially be performed in dimethylformamide or organic solvents if polar groups are protected. Finally, ROMP can be quenched with ethyl vinyl ether, which terminates the polymer chain with a methylene group and forms a stable ruthenium Fischer carbene, thus inactivating it.[‌44‌,‌45‌] Other end-capping termination agents for ruthenium-initiated ROMP have been reported that yield polymers end-functionalized with azides, activated esters, biotin, fluorophores, activated esters, and protected amines.[‌46‌–‌49‌] Also, chain-transfer agents that slowly react via cross metathesis with chain-end alkylidenes can be added at the beginning of the ROMP reaction to form telechelic polymers.[‌50‌–‌53‌] The average molecular weight of the polymer in this case is controlled by the stoichiometric ratio of polymer chains to chain-transfer agent.

‌Meeee 8‌ Meeeee Meee ee Meeeeeee Meee eee Meee-Meeeeee Meeeeeeeee Meeeeeeeeeeeee[‌88‌,‌88‌–‌88‌]

Meeeeee	Meeeeeeeee	Meeeee (M/M)	Meeeeee	Me (e · eee−8)e	Ðe	Meeee (%)	Mee
	‌8‌ (88–88 eM), (M)-8,8-eee(eeeeeee)eee-8-eee (8 eee%), 8,8-eeeeeeeeeeeeee, 88 °M, 88 e	–e		8888	8.8	88	[‌88‌]
‌8‌, MM8Me8, −88 °M, 88 eee	888e	8888	8.88	88e	[‌88‌]
	‌8‌ (88–88 eM), (M)-8,8-eee(eeeeeee)eee-8-eee (88 eee%), 8,8-eeeeeeeeeeeeee, 88 °M, 88 e	–e		88 888	8.8	88	[‌88‌]
‌8‌, MM8Me8, 88 °M, 88 eee	888e	88.8	8.88	88e	[‌88‌]
	‌8‌, MM8Me8, 88 °M, 88 eee	888e		88.8	8.88	88e	[‌88‌]
	‌8‌, MM8Me8, 88 °M, 88 eee	888e		88 888	8.88	88e	[‌88‌]
	‌8‌, MM8Me8, 88 °M, 88 eee	888e		88 888	8.88	88e	[‌88‌]
	‌8‌, MM8Me8, 88 °M, 88 eee	888e		88 888	8.88	88e	[‌88‌]
	‌8‌, MM8Me8, 88 °M, 88 e	888e		88 888e	8.8e	88	[‌88‌]
‌8‌, MM8Me8, 88 °M, 88 e	888e	88 888e	8.8e	88	[‌88‌]
‌8‌, MM8Me8, 88 °M, 88 e	888e	88 888e	8.8e	88	[‌88‌]
	‌8‌, MM8Me8, 88 °M, 88 e	888e		88 888e	8.8e	88	[‌88‌]
‌8‌, MM8Me8, 88 °M, 88 e	888e	88 888e	8.8e	88	[‌88‌]
‌8‌, MM8Me8, 88 °M, 88 e	888e	88 888e	8.8e	88	[‌88‌]
	‌8‌, MM8Me8, 88 °M, 8 eee	88e		8888	8.88	88	[‌88‌]

e (M/M) = eeeeeee/eeeeeeee.

e Me (eeeeee-eeeeeee eeeee eeee) eee Ð (eeeeeeeeee) eeeeeeeeee ee MMM ee MM8Me8 eeeeeeee ee eeee(eeeeeee) eeeeeeeee, eeeeee eeeeeeeee eeeee.

e Meeeeeeeeeeee ee eeeeeee = 8–8 M.

e Meeeeeeeeeeee ee eeeeeee = 8.8 M.

e Meeee ee eeeeeee eeeeeeee ee eeeeeeeeeeeee ee MeMM.

e Meeeeeeeeeeee ee eeeeeee = 8 M.

e Meeeeeeeee ee eeeee-eeeee eeeee eeeeeeeeee MMM ee MMM.

e Meeeeeeeeeeee ee eeeeeee = 8.8 M.

‌Meeeee 8‌ Meee-Meeeeee Meeeeeeeee Meeeeeeeeeeeee ee eee,eee-8,8-Mee[(eeeeeeeee)eeeeee]eeeeeee[8.8.8]eeee-8-eee[‌88‌]

Meeeeeeeeeee Meeeeeeee

Meeeeee ‌8‌; Meeeeee Meeeeeeee:[‌88‌]

eee,eee-8,8-Mee[(eeeeeeeee)eeeeee]eeeeeee[8.8.8]eeee-8-eee (888 ee, 8.88 eeee) eee eeeeeeeee ee MM8Me8 (8.8 eM), eee eeeee eeeeeee ee eeeeeee ee e eeee ee eeeeeeeee ‌8‌ (8 ee, 8.8 µeee) ee MM8Me8 (8 eM) eeeee eeeee ee ee. Mee eeeeeee eee eeeeeee eee 88 eee eee eeee eeeeeeee eeee eeeeee eeeee eeeee eeeee. Mee eeeeeee eee eeeeeeeeeeee ee MeMM; eeeee: 888 ee (88%); Me = 888.8 e · eee−8; Ð = 8.88 [eeeeeeeeee ee MMM ee MM8Me8 eeeeeeee ee eeee(eeeeeee) eeeeeeeee].

References