RESUMEN
A highly enantioselective Ir-catalyzed asymmetric hydrogenation of 2,5-disubstituted pyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazines containing four nitrogen atoms has been first realized. Under additive-free conditions, a variety of chiral 2,5-disubstituted 5,6-dihydropyrrolo[1,2-a][1,2,4]triazolo[5,1-c]pyrazines can be afforded in high yields (86-98%) with excellent enantioselectivities of up to 99% ee. This method provides a straightforward strategy for the efficient synthesis of chiral multinitrogen polyheterocyclic compounds.
RESUMEN
Rh-catalyzed asymmetric hydrogenation of 2-substituted 4H-thiochromenes and 4H-chromenes was successfully developed. This method provided highly efficient access to a series of chiral 2-substituted thiochromanes and chromanes in high yields with excellent enantioselectivities (up to 99% yield, 86-99% ee). The obtained chiral 2-substituted thiochromane products were also successfully transformed to corresponding chiral α-substituted sulfoxides and sulfones with excellent enantioselectivities. Furthermore, this highly enantioselective hydrogenation process could be successfully applied to the concise and practical synthesis of the chiral pharmaceutical BW683C.
RESUMEN
Halide exchange of (Cp3tms)2ThCl2 (1; Cp3tms = η5-1,2,4-(Me3Si)3C5H2) with Me3SiI furnishes (Cp3tms)2ThI2 (2), which is then reduced with potassium graphite (KC8) in the presence of 2,2'-bipyridine to give the thorium bipyridyl metallocene (Cp3tms)2Th(bipy) (3) in good yield. Complex 3 was fully characterized and readily reacted with various small molecules. For example, 3 may serve as a synthetic equivalent for the (Cp3tms)2Th(II) fragment when exposed to CuI, Ph2S2, organic azides, and CS2. Moreover, upon the addition of thiobenzophenone Ph2CS, p-methylbenzaldehyde (p-MeC6H4)CHO, benzophenone Ph2CO, amidate PhCONH(p-tolyl), seleno-ketone (p,p'-dimethoxy), selenobenzophenone (p-MeOPh)2CSe, di(p-tolyl)methanimine (p-tolyl)2CâNH, 1,2-di(benzylidene)hydrazine (PhCHâN)2, and nitriles PhCN, PhCH2CN, and Ph2CHCN C-C coupling results to give (Cp3tms)2Th[(bipy)(Ph2CS)] (8), (Cp3tms)2Th[(bipy)(p-MePhCHO)] (9), (Cp3tms)2Th[(bipy)(Ph2CO)] (10), (Cp3tms)2Th[(bipy){(p-tolylNH)(Ph)CO}] (11), (Cp3tms)2Th[(bipy){(p-MeOPh)2CSe}] (12), (Cp3tms)2Th[(bipy){(p-tolyl)2CNH}] (13), (Cp3tms)2Th[(bipy)(PhCHNNâCHPh)] (14), (Cp3tms)2Th[(bipy)(PhCN)] (16), (Cp3tms)2Th[(bipy)(PhCH2CN)] (17), and (Cp3tms)2Th[(bipy)(Ph2CHCN)] (18), respectively. However, when thiazole is added to 3, the dimeric sulfido complex [(Cp3tms)2Th]2[µ-(bipy)CH2NCHCHS]2 (15) can be isolated. Moreover, the addition of isonitriles such as Me3CNC and PhCH2NC to 3 results in C-N bond cleavage and C-C coupling processes to form the thorium isocyanido amido complexes (Cp3tms)2Th[4-(Me3C)bipy](NC) (19) and (Cp3tms)2Th[4-(PhCH2)bipy](NC) (20), respectively. Nevertheless, upon exposure of 3 to (trimethylsilyl)diazomethane Me3SiCHN2, the bis-amido complex (Cp3tms)2Th[5,6-(Me3SiCH)bipy] (21), concomitant with N2 release, is isolated.
RESUMEN
The structure of and bonding in two base-free terminal actinide imido metallocenes, [η5-1,2,4-(Me3C)3C5H2]2AnâN(p-tolyl) (An = U (1), Th (1')) are compared and connected to their individual reactivity. While structurally rather similar, the U(IV) derivative 1 is slightly more sterically crowded. Furthermore, density functional theory (DFT) studies imply that the 5f orbital contribution to the bonding within the individual actinide imido AnâN(p-tolyl) moieties is significantly larger for 1 than for 1', which makes the bonds between the [η5-1,2,4-(Me3C)3C5H2]2U2+ and [(p-tolyl)N]2- fragments more covalent. Therefore, steric and electronic factors impact the reactivity of these imido complexes. For example, complex 1 is inert toward internal alkynes, but it readily forms Lewis base adducts [η5-1,2,4-(Me3C)3C5H2]2UâN(p-tolyl)(L) (L = OPMe3 (6), dmap (9), PhCN (14), and 2,6-Me2PhNC (17)) with Me3PO, 4-dimethylaminopyridine (dmap), nitrile, PhCN, or isonitrile 2,6-Me2PhNC. It may also react as a nucleophile or undergo a [2 + 2] cycloaddition with CS2, isothiocyanates, thio-ketones, ketones, lactides, and acyl nitriles, forming the four- or five-membered metallaheteroacycles, terminal sulfido, or oxido complexes, and cyanide amidate complexes, respectively. In contrast, after the addition of aldehyde p-tolylCHO, the tetranuclear complex [η5-1,2,4-(Me3C)3C5H2]4[OCH(p-tolyl)CH(p-tolyl)O]2U4O4 (10) is isolated. However, while 1 is unreactive toward dicyclohexylcarbodiimide (DCC), an equilibrium exists in benzene solution between N,N'-diisopropylcarbodiimide (DIC), 1, and the four-membered metallaheterocycle [η5-1,2,4-(Me3C)3C5H2]2U[N(p-tolyl)C(âNiPr)N(iPr)] (12). Furthermore, 1 may also engage in single- and two-electron transfer processes. It is singly oxidized by Ph3CN3, CuI, Ph2S2, and Ph2Se2, yielding the uranium(V) imido complexes [η5-1,2,4-(Me3C)3C5H2]2UâN(p-tolyl)(X) (X = N3 (20), I (22), PhS (23), and PhSe (24)), or is doubly oxidized by organic azides (RN3) and 9-diazofluorene, forming the uranium(VI) bis-imido metallocenes [η5-1,2,4-(Me3C)3C5H2]2UâN(p-tolyl)(=NR) (R = p-tolyl (18), mesityl (19)) and [η5-1,2,4-(Me3C)3C5H2]2U=N(p-tolyl)[=NN=(9-C13H8)] (21), respectively.
RESUMEN
Uranium diazomethanediide complexes can be prepared and their synthesis, structure and reactivity were explored. Reaction of the uranium imido compound [η5 -1,2,4-(Me3 Si)3 C5 H2 ]2 U=N(p-tolyl)(dmap) (1) or [η5 -1,3-(Me3 C)2 C5 H3 ]2 U=N(p-tolyl)(dmap) (4) with Me3 SiCHN2 cleanly yields the first isocyanoimido metal complexes [η5 -1,2,4-(Me3 Si)3 C5 H2 ]2 U(=NNC)(µ-CNN=)U(dmap)[η5 -1,2,4-(Me3 Si)3 C5 H2 ]2 (2) and {[η5 -1,3-(Me3 C)2 C5 H3 ]2 U[µ-(=NNC)]}6 (5), respectively. Both compounds exhibit remarkable thermal stability and were fully characterized. According to density functional theory (DFT) studies the bonding between the Cp2 U2+ and [NNC]2- moieties is strongly polarized with a significant 5 f orbital contribution, which is also reflected in the reactivity of these complexes. For example, complex 5 acts as a nucleophile toward alkylsilyl halides and engages in a [2+2] cycloaddition with CS2 , but no reaction occurs in the presence of internal alkynes.
RESUMEN
Rh-(R,R)-f-spiroPhos complex-catalyzed asymmetric hydrogenation of α-substituted alkenyl sulfones has been achieved, affording the chiral γ-keto sulfones and simple α-alkyl-substituted sulfones in high yields (96-99%) with excellent chemo-/enantioselectivities (86-96% ee) and high turnover numbers (TONs) of up to 4000. The method provides an efficient and high-enantioselectivity strategy for chiral γ-keto sulfones and simple α-substituted sulfones under mild conditions. Moreover, the obtained hydrogenation product was transformed into other important chiral α-substituted sulfones.
RESUMEN
The Lewis base-supported uranium terminal imido metallocene [η5-1,2,4-(Me3Si)3C5H2]2UîN(p-tolyl)(dmap) (1) readily reacts with various small molecules such as internal alkynes, isothiocyanates, thioketones, amidates, organic nitriles and imines, chlorosilanes, copper iodide, diphenyl disulfide, organic azides and diazoalkane derivatives. For example, treatment of 1 with PhCîCCîCPh and PhNCS forms metallaheterocycles originating from a [2 + 2] cycloaddition to yield [η5-1-(p-tolyl)NC(Ph)îCHCîC(Ph)CH2Si(Me)2-2,4-(Me3Si)2C5H2][η5-1,2,4-(Me3Si)3C5H2]U (2) and [η5-1,2,4-(Me3Si)3C5H2]2U[N(p-tolyl)C(îNPh)S](dmap) (3), respectively. The reaction of 1 with the thioketone Ph2CS forms the known uranium sulfido complex [η5-1,2,4-(Me3Si)3C5H2]2US(dmap) (4), which reacts with a second molecule of Ph2CS to give the disulfido compound [η5-1,2,4-(Me3Si)3C5H2]2U(S2CPh2) (5). The imido moiety also promotes deprotonation reactions as illustrated in the reactions with the amide PhCONH(p-tolyl), the nitrile PhCH2CN and the imine (p-tolyl)2CîNH to form the bis-amidate [η5-1,2,4-(Me3Si)3C5H2]2U[OC(Ph)N(p-tolyl)]2 (7), and the iminato complexes [η5-1,2,4-(Me3Si)3C5H2]2U[N(p-tolyl)C(CH2Ph)îNH](NîCîCHPh) (8) and [η5-1,2,4-(Me3Si)3C5H2]2U[NH(p-tolyl)][NîC(p-tolyl)2] (9), respectively. Addition of PhSiH2Cl to 1 yields [η5-1,2,4-(Me3Si)3C5H2]2U(Cl)[N(p-tolyl)SiH2Ph] (10). In contrast, the uranium(V) imido complexes [η5-1,2,4-(Me3Si)3C5H2]2UîN(p-tolyl)(I) (11) and [η5-1,2,4-(Me3Si)3C5H2]2UîN(p-tolyl)(SPh) (12), may be isolated upon addition of CuI or Ph2S2 to 1, respectively. Uranium(VI) bis-imido metallocenes [η5-1,2,4-(Me3Si)3C5H2]2UîN(p-tolyl)(îNR) (R = p-tolyl (13), mesityl (14)) and [η5-1,2,4-(Me3Si)3C5H2]2UîN(p-tolyl)[îNNî(9-C13H8)] (15) are accessible from 1 on exposure to RN3 (R = p-tolyl, mesityl) and 9-diazofluorene, respectively. Complexes 2, 3, 5, and 7-15 were characterized by various spectroscopic techniques and, in addition, compounds 2, 3, 5, and 7-13 were structurally authenticated by single-crystal X-ray diffraction analyses.
RESUMEN
A highly enantioselective rhodium-catalyzed reductive dearomatization of 7-substituted pyrazolo[1,5-a]pyrimidines has been realized for the first time by two strategies to afford chiral 4,5,6,7-tetrahydropyrazolo[1,5-a]pyrimidines with excellent enantioselectivities of up to 98% ee. This method also provides an efficient approach for the synthesis of the powerful BTK inhibitor, zanubrutinib.
RESUMEN
Terminal uranium oxido, sulfido, and selenido metallocenes were synthesized, and their reactivity was comprehensively studied. Heating of an equimolar mixture of [η5-1,2,4-(Me3Si)3C5H2]2UMe2 (2) and [η5-1,2,4-(Me3Si)3C5H2]2U(NH-p-tolyl)2 (3) in the presence of 4-dimethylaminopyridine (dmap) in refluxing toluene forms [η5-1,2,4-(Me3Si)3C5H2]2UâN(p-tolyl)(dmap) (4), which is a useful precursor for the preparation of the terminal uranium oxido, sulfido, and selenido metallocenes [η5-1,2,4-(Me3Si)3C5H2]2UâE(dmap) (E = O (5), S (6), Se (7)) employing a cycloaddition-elimination methodology with Ph2CâE (E = O, S) or (p-MeOPh)2CSe, respectively. Metallocenes 5-7 are inert toward alkynes, but they act as nucleophiles in the presence of alkylsilyl halides. The oxido and sulfido metallocenes 5 and 6 undergo [2 + 2] cycloadditions with isothiocyanate PhNCS or CS2, while the selenido derivative 7 does not. The experimental studies are complemented by density functional theory (DFT) computations.
RESUMEN
An efficient Ni-(S,S)-Ph-BPE complex that catalyzed asymmetric hydrogenation of cyclic N-acyl hydrazones has been developed to produce various chiral cyclic hydrazines in high yields with excellent enantioselectivities of up to >99% enantiomeric excess. Moreover, the hydrogenation can not only proceed smoothly on a gram scale under lower catalyst loading (S/C = 3000) without any decrease of enantioselectivity but can also be applied to the asymmetric synthesis of a RIP-1 kinase inhibitor.
RESUMEN
The uranium metallacyclocumulene, [η5-1,3-(Me3Si)2C5H3]2U(η4-C4Ph2) (3) was isolated from the reaction mixture containing [η5-1,3-(Me3Si)2C5H3]2UCl2 (1), potassium graphite (KC8) and 1,4-diphenylbutadiyne (PhCîC-CîCPh) in good yield. The reactivity of 3 towards various small organic molecules was evaluated. For example, while complex 3 shows no reactivity towards alkynes and 2,2'-bipyridine, it may deliver the [η5-1,3-(Me3Si)2C5H3]2U(II) fragment in the presence of Ph2E2 (E = S, Se) and Ph3CN3, or react as a nucleophile in the presence of carbodiimides, isothiocyanates, aldehydes, ketones, and pyridine derivatives, forming five-, seven- or nine-membered heterometallacycles. On the contrary, addition of Ph2CS to 3 induces CîS bond cleavage yielding the dithiolate complex [η5-1,3-(Me3Si)2C5H3]2U[S2(C12H5Ph5)] (14). In contrast, the closely related, but sterically more encumbered uranium metallacyclocumulene [η5-1,2,4-(Me3Si)3C5H2]2U(η4-C4Ph2) (4) features a more limited reactivity which is restricted to mono- and double insertions with small unsaturated organic molecules such as isothiocyanates, ketones and nitriles.
RESUMEN
A highly efficient asymmetric hydrogenation of a series of γ-keto acid derivatives, including γ-keto acids, esters, and amides, using a Ni-(R,R)-QuinoxP* complex as the catalyst has been developed to afford chiral γ-hydroxy acid derivatives with excellent enantioselectivities, up to 99.9% ee. This method provides not only an economical one-pot approach for the synthesis of chiral γ-lactones but also access to (S)-norfluoxetine, an inhibitor of neural serotonin reuptake and an essential intermediate for pharmaceutical synthesis.
Asunto(s)
Amidas , Ésteres , Catálisis , Hidrogenación , Hidroxiácidos , Cetoácidos , Lactonas , Níquel , EstereoisomerismoRESUMEN
The uranium bipyridyl metallocene, [η5-1,3-(Me3Si)2C5H3]2U(bipy) (2), is readily accessible in good yield by adding potassium graphite (KC8) to a mixture of [η5-1,3-(Me3Si)2C5H3]2UCl2 (1) and 2,2'-bipyridine. Compound 2 was fully characterized and employed for small-molecule activation. It has been demonstrated that 2 may serve as a synthon for [η5-1,3-(Me3Si)2C5H3]2U(II) fragment in the presence of Ph2E2 (E = S, Se), alkynes, and a variety of hetero-unsaturated molecules such as diazabutadienes, azine (Ph2CâN)2, o-benzoquinone, pyridine N-oxide, CS2, isothiocyanates, and organic azides. However, upon exposure of 2 to thio-ketone Ph2CS, aldehyde p-MePhCHO, ketone Ph2CO, imine PhCHâNPh, azine (PhCHâN)2, and nitrile PhCN, it may also promote C-C coupling reactions forming [η5-1,3-(Me3Si)2C5H3]2U[(bipy)(Ph2CS)] (16), [η5-1,3-(Me3Si)2C5H3]2U[(bipy)(p-MePhCHO)] (17), [η5-1,3-(Me3Si)2C5H3]2U[(bipy)(Ph2CO)] (18), [η5-1,3-(Me3Si)2C5H3]2U[(bipy)(PhCHNPh)] (19), [η5-1,3-(Me3Si)2C5H3]2U[(bipy)(PhCHNNâCHPh)] (20), and [η5-1,3-(Me3Si)2C5H3]2U[(N2C10H7C(Ph)NH)] (22), respectively, in quantitative conversion. Furthermore, in the presence of CuI, a single-electron transfer (SET) process is observed to yield the uranium(III) iodide complex [η5-1,3-(Me3Si)2C5H3]2U(I)(bipy) (15).
RESUMEN
The first asymmetric hydrogenation of ß,ß-diaryl unsaturated phosphonates has been realized for synthesis of ß,ß-diaryl chiral phosphonates with excellent enantioselectivities (up to 99.9% ee) catalyzed by the Rh-(R,R)-f-spiroPhos complex. Furthermore, this catalyst also exhibits comparably excellent performance for ß-aryl-ß-alkyl unsaturated phosphonates providing the corresponding chiral phosphonates with up to 99.9% ee values. This methodology provides a straightforward access to asymmetric synthesis of chiral phosphonates.
RESUMEN
This paper describes the synthesis and reactivity of [η5-1,3-(Me3Si)2C5H3]2U(îP-2,4,6-iPr3C6H2)(OPMe3) (6) which is accessible from a ligand exchange reaction between [η5-1,3-(Me3Si)2C5H3]2U(îP-2,4,6-iPr3C6H2)(OPPh3) (2) and Me3PO at ambient temperature. Phosphinidene 6 exhibits no reactivity towards internal alkynes, but readily reacts with various hetero-unsaturated molecules such as isothiocyanates, aldehydes, nitriles, isonitriles, and organic azides, forming uranium sulfido, oxido, imido, and uranaheterocyclic compounds. Nevertheless, with the bidentate ortho-dicyanobenzene o-C6H4(CN)2 the zwitterionic species [η5-1,3-(Me3Si)2C5H3]2U[NHC(N){C6H4CP(2,4,6-iPr3C6H2)CH2PMe2O}] (13) is isolated in good yield. Moreover, 6 converts with Ph2S2 to the uranium(III) phenylthiolate compound [η5-1,3-(Me3Si)2C5H3]2USPh(OPMe3) (7) in good isolated yield. Furthermore, the influence of the Lewis base on the reactivity of the uranium phosphinidene metallocenes has also been evaluated.
RESUMEN
An enantioselective hydrogenation of 5-alkylidene-2,4-diketoimidazolidines (hydantoins) and 3-alkylidene-2,5-ketopiperazines catalyzed by the Rh/f-spiroPhos complex under mild conditions has been developed, which provides an efficient approach to the highly enantioselective synthesis of chiral hydantoins and 2,5-ketopiperazine derivatives with high enantioselectivities up to 99.9% ee.
RESUMEN
The Lewis base supported terminal uranium phosphinidene metallocene [η5-1,3-(Me3C)2C5H3]2U([double bond, length as m-dash]P-2,4,6-iPr3C6H2)(OPMe3) (2) could be isolated from a salt metathesis reaction in toluene at ambient temperature between [η5-1,3-(Me3C)2C5H3]2U(Cl)Me (1) and 2,4,6-iPr3C6H2PHK in the presence of Me3PO, and its structure and reactivity were probed in detail. No reaction of 2 with internal alkynes was observed, but it reacts in the presence of various heterounsaturated molecules such as CS2, isothiocyanates, aldehydes, imines, diazenes, carbodiimides, nitriles, isonitriles, diazoalkane, and organic azides, forming carbodithioates, sulfidos, oxidos, metallaheterocycles, and imido complexes, in good yields. Moreover, on reaction with the diazoalkane derivative Me3SiCHN2 the pseudophosphinimido uranium(iii) complex [η5-1,3-(Me3C)2C5H3]2U(N[double bond, length as m-dash]P-2,4,6-iPr3C6H2)(OPMe3) (20) can be isolated in good yield.
RESUMEN
The synthesis, electronic structure, and reactivity of a uranium metallacyclopropene were comprehensively studied. Addition of diphenylacetylene (PhC≡CPh) to the uranium phosphinidene metallocene [η5 -1,2,4-(Me3 C)3 C5 H2 ]2 U=P-2,4,6-tBu3 C6 H2 (1) yields the stable uranium metallacyclopropene, [η5 -1,2,4-(Me3 C)3 C5 H2 ]2 U[η2 -C2 Ph2 ] (2). Based on density functional theory (DFT) results the 5f orbital contributions to the bonding within the metallacyclopropene U-(η2 -C=C) moiety increases significantly compared to the related ThIV compound [η5 -1,2,4-(Me3 C)3 C5 H2 ]2 Th[η2 -C2 Ph2 ], which also results in more covalent bonds between the [η5 -1,2,4-(Me3 C)3 C5 H2 ]2 U2+ and [η2 -C2 Ph2 ]2- fragments. Although the thorium and uranium complexes are structurally closely related, different reaction patterns are therefore observed. For example, 2 reacts as a masked synthon for the low-valent uranium(II) metallocene [η5 -1,2,4-(Me3 C)3 C5 H2 ]2 UII when reacted with Ph2 E2 (E=S, Se), alkynes and a variety of hetero-unsaturated molecules such as imines, ketazine, bipy, nitriles, organic azides, and azo derivatives. In contrast, five-membered metallaheterocycles are accessible when 2 is treated with isothiocyanate, aldehydes, and ketones.
RESUMEN
A Lewis base supported terminal uranium phosphinidene, [η5-1,3-(Me3C)2C5H3]2U(âP-2,4,6-tBu3C6H2)(OPMe3) (5), is isolated from the reaction of the uranium methyl chloride [η5-1,3-(Me3C)2C5H3]2U(Cl)Me (4) with 2,4,6-(Me3C)3C6H2PHK in toluene in the presence of Me3PO. Moreover, the reactivity of uranium phospinidene 5 toward a series of small molecules was comprehensively explored. While no reactivity of 5 with internal alkynes is observed attributed to steric hindrance, it readily reacts in good yields with various small molecules including isothiocyanates, aldehydes, imines, diazenes, carbodiimides, nitriles, isonitriles, and organic azides, yielding uranium sulfidos, oxidos, metallaheterocycles, and imido complexes.
RESUMEN
The first stable base-free terminal uranium phosphinidene metallocene is presented; and its structure and reactivity have been studied in detail and compared to that of the corresponding thorium derivative. Salt metathesis reaction of the methyl iodide uranium metallocene Cp'''2 U(I)Me (2, Cp'''=η5 -1,2,4-(Me3 C)3 C5 H2 ) with Mes*PHK (Mes*=2,4,6-(Me3 C)3 C6 H2 ) in THF yields the base-free terminal uranium phosphinidene metallocene, Cp'''2 U=PMes* (3). In addition, density functional theory (DFT) studies suggest substantial 5f orbital contributions to the bonding within the uranium phosphinidene [U]=PAr moiety, which results in a more covalent bonding between the [Cp'''2 U]2+ and [Mes*P]2- fragments than that for the related thorium derivative. This difference in bonding besides steric reasons causes different reactivity patterns for both molecules. Therefore, the uranium derivative 3 may act as a Cp'''2 U(II) synthon releasing the phosphinidene moiety (Mes*P:) when treated with alkynes or a variety of hetero-unsaturated molecules such as imines, thiazoles, ketazines, bipy, organic azides, diazene derivatives, ketones, and carbodiimides.