title: Tailor made mixed-metal reagents for metalation/C-C bond forming processes
Creators: name: Mastropierro, Pasquale
Publisher: name: Universität Bern
Year: 2022
Subjects: subject: 540 Chemistry
subject: 570 Life sciences; biology

description: The thesis focusses on advancing the understanding on cooperative effects heterobimetallic compounds which combine an alkali-metal with a divalent metal such as magnesium, zinc and manganese. Through rational design, several alkali-metal ates have been prepared and structurally authenticated. Their applications towards two fundamental organic transformations, namely, deprotonative metallation and metal-halogen exchange have been investigated.

Chapter 2 discloses a new family of sodium zincates containing the bulky chelating silyl(bis) amide {Ph2Si(NAr*)2}2¯ (Ar*= 2,6-diisopropylphenyl). Illustrating the enhanced kinetic basicity of Zn-N bonds versus Zn-C bonds, reacting Ph2Si(NHAr*)2 (1) with an equimolar mixture of NaCH2SiMe3 and Zn(HMDS)2 (HMDS= N(SiMe3)2) furnished alkyl sodium zincate [{(Ph2Si(NAr*)2)Zn(CH2SiMe3)}¯{Na(THF)6}+] (3). Contrastingly using a stepwise approach, by treating 1 first with NaCH2SiMe3 afforded sodium amide [{Ph2Si(NHAr*)(NAr*)Na}2] (5), which can subsequently undergo co-complexation with Zn(HMDS)2, favouring the metallation of the remaining NHAr* group to give heteroleptic tris(amido) zincate [{(Ph2Si(NAr*)2)Zn(HMDS)}¯{Na(THF)6}+] (6). The reactivity of sodium zincates 6, 3 and [NaZn(CH2SiMe3)3] (4) towards 2,4,6-trimethylacetophenone led to the isolation of enolate complexes [{(THF)NaZn(OC(=CH2)Mes)3}2] (9), [{(THF)NaZn(CH2SiMe3)(OC(=CH2)Mes)2}2] (8), and [{(THF)Na(OC(=CH2)Mes)}4] (10) (Mes= 2,4,6 trimethylphenyl), respectively. These studies revealed that the chelating silyl(bis)amide {Ph2Si(NAr*)2}2− far from being an innocent spectator is an effective base for the deprotonation of this ketone, showing an unexpected superior kinetic basicity than the CH2SiMe3 alkyl group when part of sodium heteroleptic zincate 3. The bimetallic constitution of enolates 9 and 8 contrasts with that of all-sodium 10, which is formed with concomitant elimination of Zn(CH2SiMe3)2. Revealing the divergent behaviour of Mg versus Zn in these bimetallic systems, reaction of 2,4,6-trimethylacetophenone with the magnesium analogue of 3, [{Ph2Si(NAr*)2Mg(CH2SiMe3)}−{Na(THF)6}+] (11), produces magnesiate enolate [{Ph2Si(NAr*)2Mg(O(=CH2)Mes)(THF)}−{Na(THF)5}+] (12), where the chelating silyl(bis)amide ligand is retained and metalation of the ketone is actioned by the alkyl group.

Chapter 3 exploits the sequential deprotonative co-complexation approach developed in Chapter 2 to access novel potassium metal(ates). Thus, monometallation of 1 is accomplished using potassium alkyl KCH2SiMe3 yielding [{Ph2Si(NHAr*)(NAr*)K}∞] (13), which, in turn, undergoes co-complexation with the relevant M(CH2SiMe3)2 (M=Mg, Zn, Mn) enabling metallation of the remaining NHAr* group to furnish silylbis(amido) alkyl potassium metal(ates) [{Ph2Si(NAr*)2M(THF)x(CH2SiMe3)}−{K(THF)y}+] (M=Zn, x=0, y=4, 14; M=Mg, x=1, y=3, 15; and M=Mn, x=0, y=4, 16). Reactivity studies of potassium manganate 16 with the amine HMDS(H) revealed the kinetic activation of the remaining alkyl group on Mn furnishing [K(THF)2{Ph2Si(NAr*)2}Mn(HMDS)] (18). Similarly 16 reacts with phenyl acetylene to give [{Ph2Si(NAr*)2Mn(THF)(C≡CPh)}¯{K(THF)3}+] (17). The structures of these bimetallic complexes along with that of the potassium precursor 13 have been established by X-ray crystallographic studies.

Chapter 4 introduces a new type of heterobimetallic base, the specially designed potassium zincate [{Ph2Si(NAr*)2Zn(TMP)}¯{K(THF)6+] (19) which combines a sterically demanding silyl(bis)amide ligand with a kinetically activated terminal TMP amide group (TMP= 2,2,6,6-tetramethylpiperidide). Circumventing common limitations of conventional s-block metallating bases, 19 enables efficient and regioselective zincation of a broad range of substituted fluoroarenes including hypersensitive fluoronitrobenzene derivatives. Trapping and characterization of the organometallic species involved in these reactions [{Ph2Si(NAr*)2Zn(ArF)}¯{K(THF)x+] (ArF =C6H2F3, C6H3F2, C6H2Cl3, C6H2F2NO2, C6H3FNO2, C11H6F2N, C5H3FN, C6F5, C6HF4 and C6F4; x= 3-6) has provided informative mechanistic insights on how these direct zincation reactions may occur as well as shed light on the key role of the supporting silyl(bis)amido ligand. The first examples of directly metalated nitroarenes to be structurally characterised have been presented as well as the ability of this approach to promote polyzincations of fluoroarenes has been disclosed. Expanding the synthetic potential of this heterobimetallic approach it has been shown that these organometallic compounds can engage in onward C-C bond forming processes.

Chapter 5 explores the synthesis and reactivity of higher order manganates [(TMEDA)2AM2Mn(CH2SiMe3)4] (AM= Li, 37; Na, 43; K; TMEDA= N,N,N’,N’-tetramethylethylenediamine) to promote Mn-I exchange /alkyne metallation reactions in tandem with oxidative homocoupling reactions. Lithium manganate 37 enables the efficient direct Mn–I exchange of aryliodides, affording transient (aryl)lithium manganate intermediates which in turn undergo spontaneous C−C homocoupling at room temperature to furnish symmetrical (bis)aryls in good yields under mild reaction conditions. The combination of EPR with X-ray crystallographic studies has revealed the mixed Li/Mn constitution of the organometallic intermediates involved in these reactions, including the homocoupling step which had previously been thought to occur via a single-metal Mn aryl species. These studies show Li and Mn working together in a synergistic manner to facilitate both the Mn–I exchange and the C−C bond-forming steps. Both steps are carefully synchronized, with the concomitant generation of the alkyliodide ICH2SiMe3 during the Mn–I exchange being essential to the aryl homocoupling process, wherein it serves as an in situ generated oxidant. Sodium manganate 43 reacts with 4 equivalents of phenylacetylene to give [(THF)4Na4Mn2(C≡CPh)8] (45) which when exposed to dry air furnishes the relevant 1,3 enyne in a 97% yield.