ISSN 2518-1548 (Online) Журнал органічної та фармацевтичної хімії. – 2020. – Т. 18, вип. 3 (71) ISSN 2308-8303 (Print) UDC 547.316+54.057 https://doi.org/10.24959/ophcj.20.199828 E. D. Butova1, V. V. Bahonsky1,2, R. I. Yurchenko1, S. O. Butov1, M. M. Moroz1, A. A. Fokin1 1 National Technical University of Ukraine “Igor Sikorsky Kyiv Polytechnic Institute”, Ukraine 37, Peremohy Ave., Kyiv, 03056, Ukraine. E-mail: [email protected] 2 Justus Liebig University Giessen, Germany P-Stereogenic diamondoid phosphines Despite diamondoid phosphines have found many synthetic applications and are even available commer- cially the chemistry of chiral diamondoid phosphines remains largely unexplored. Aim. To develop the convenient preparative method for the preparation of sterically-congested P-stereogenic secondary diamodoidyl phosphines as potential organocatalysts and ligands in the asymmetric synthesis. Results and discussion. A convenient method for the synthesis of P-stereogenic diamondoid phosphines with high yields through the phosphorylation of hydroxydiamondoids in trifluoroacetic acid followed by the re- duction of the corresponding asymmetric chlorophosphonates has been proposed. The secondary phosphines obtained form stable complexes with borane that can be used to separate diamondoid phosphines into enan- tiomers. Experimental part. The experimental procedures for the preparation of 1- and 4-diamantyl-1-adamantyl- and phenylphosphines were developed; the structures of new compounds were confirmed by NMR and HRMS spectral data. Conclusions. A number of P-stereogenic mixed diamondoidylaryl phosphines and the secondary phos- phines containing exclusively diamondoid substituents has been prepared. A degree of steric bulkiness is deter- mined by the combination of diamondoid substituents around a phosphorus atom where 1-diamantyl derivatives are the most sterically-congested. The compounds obtained are potential ligands in asymmetric catalysis. Key words: phosphine borane complexes; 1-adamantyldiamantylphosphine; 4-adamantyldiamantylphosphine; 1-phenyldiamantylphosphine; 4-phenyldiamantylphosphine; P-stereogenic phosphines К. Д. Бутова1, В. В. Бахонський1,2, Р. І. Юрченко1, С. О. Бутов1, М. М. Мороз1, А. А. Фокін1 1 НТУУ «Київський політехнічний інститут імені Ігоря Сікорського», Україна 2 Гіссенський університет імені Юстуса Лібіха, Німеччина Р-стереогенні діамандоїдні фосфіни Незважаючи на те, що діамандоїдні фосфіни широко використовуються в органічному синтезі і навіть доступні комерційно, хімія хіральних діамандоїдних фосфінів залишається не дослідженою. Мета. Розробити зручний препаративний метод синтезу стереоускладнених Р-стереогенних вторин- них діамандоїдних фосфінів, які можуть бути використані як ліганди в асиметричному синтезі, а також як органокаталізатори. Результати та їх обговорення. Запропоновано зручний метод синтезу P-стереогенних діамандоїдних фосфінів шляхом фосфорилювання гідроксипохідних діамандоїдів у трифтороцтовій кислоті з подальшим відновленням відповідних асиметричних хлорофосфонатів з високими виходами. Одержані таким чином фосфіни утворюють стійкі комплекси з бораном, які розглядаються як проміжні сполуки для подальшого розділення енантіомерів. Експериментальна частина. Був розроблений препаративний метод синтезу 1- і 4-діамантил-, 1-ада- мантил- і фенілфосфінів, структури яких підтверджено мас-спектрометричними і ЯМР-спектральними да- ними. Висновки. Одержано ряд Р-стереогенних змішаних діамандоїларилфосфінів та вторинних фосфінів, які містять виключно діамандоїдні замісники. Ступінь стеричного навантаження сполук визначається ком- бінацією діамандоїдних замісників навколо атома фосфору, де похідні 1-діамантилу найбільш стерично ускладнені. Одержані сполуки є потенційними лігандами в асиметричному каталізі. Ключові слова: боранові комплекси фосфінів; 1-адамантилдіамантилфосфін; 4-адамантилдіамантилфосфін; 1-фенілдіамантилфосфін; 4-фенілдіамантилфосфін; Р-стереогенні фосфіни Copyright © 2020, E. D. Butova, V. V. Bahonsky, R. I. Yurchenko, S. O. Butov, M. M. Moroz, A. A. Fokin This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0) Organophosphorus compounds are among useful rectly on the phosphorus” [1]. Accordingly, over the last ligands in catalysts where further progress is largely decades many chiral tertiary phosphines trademar- associated with P-stereogenic phosphines as stated ked as Quinox-P, Benz-P, Pincer-P, and some by W. Knowles in his Nobel Lecture: “…if one wanted others [2] become available commercially. These li- to get high values, the asymmetry would have to be di- gands allow obtaining high yields and enantiomeric 35 ISSN 2308-8303 (Print) Journal of Organic and Pharmaceutical Chemistry. – 2020. – Vol. 18, Iss. 3 (71) ISSN 2518-1548 (Online) phines containing phenyl, adamantyl, and diamantyl 1. HNO 3 OH + groups. The key starting compounds – 1-hydroxydia- 2. H SO , H O 2 4 2 mantane 2a and 4-hydroxydiamantane 2b were pre- 3. Chromatographic separation pared from diamantane 1 through the nitroxylation OH with the concentrated nitric acid and further acidic 1 2a 2b hydrolysis as previously described [16] (Scheme 1). Scheme 1. The synthesis of 1- and 4-hydroxydiamantanes 2a,b were converted to the cor- responding chlorophosphonates 3ad, 3bd, 3ac, and excesses of products in various transformations in- 3bcHydroxydiamantanes volving hydroacylations [3, 4], catalytic asymmetric roacetic acid [17, 18] utilizing PhPCl2 and AdPCl2 as hydrogenations [5, 6] and many others [7]. phosphorylatingthrough the phosphorylationagents (Scheme 2). reaction Chlorophospho in trifluo-- Achiral bulky diadamantyl alkyl phosphines have been nates 3ad, 3bd, 3ac, and 3bc were further reduced introduced as effective ligands where Ad2P(nBu) and 4 in tetrahydrofuran to give phosphines 4ad, Ad2PBn are now commercially available as cataCXiumA 4bd, 4ac, and 4bc. Stability towards oxygen is an im- and cataCXiumABn, respectively. The palladium complex portantwith LiAlH factor that determines the practical poten- with Ad2P(n tial of phosphine ligands. In contrast to the primary catalyst in Suzuki reactions for aryl chlorides [8], in diamondoid phosphines that were reactive towards Bu) as a ligand acts as a highly efficient oxygen, the secondary diamondoid phosphines even coupling [10] and for the arylations of ketones [11]. with one diamantyl group (4ac and 4bc) were quite Thethe arylationNa2PdCl4/Ad reactions2PBn system [9], in has Buchwald−Hartwig been successfully persistent towards oxidation. Nevertheless, for puri- applied for the Sonogashira coupling [12]. Extremely via column chromatography phosphines 4ad, bulky Ad3P in the presence of palladium acetate was 4bd, 4ac, and 4bc were converted into boron comp- recently used as a catalyst for the arylation of unsa- lexesfications 5ad, 5bd, 5ac, and 5bc 3 turated cyclic ketoethers [13]. The chemistry of chiral The structures of the phosphines obtained we- diamondoid phosphines still remains almost unex- re proven by a number of spectral in the BH characteristics./THF system. plored. Only recently the rhodium complex of di-1-ada- The 13C NMR DEPT 135 spectrum of 4-diamantyl- mantylphosphino-(tert-butylmethylphosphino)me- 1-adamantylphosphine borane 5bd contained four thane (BulkyP*) was prepared and tested as a ligand 2 for Rh-promoted asymmetric hydrogenations of the axial symmetry of diamondoid fragments. In cont- functionalized alkenes where effective transforma- rast,CH , fourthe 13 CH,C NMR and spectrum two C resonances. of 5ad contained It agrees ten with re- tions were achieved under very low catalyst loadings sonances of the prochiral 1-diamantyl moiety due to the presence of the chiral P-center in the structure. All above makes important the preparation of P-ste- The NMR spectra of complexes 5ac and 5bc displa- reogenic(< 0.001 mol %)diamondoid [14]. phosphines since the incorpo- yed a dynamic behavior and were measured under ration of bulky substituents into phosphine may en- cooling. hance the catalytic activity and selectivity of the ca- The borane protecting group can further be remo- talyst. Previously, we prepared a number of P-stereo- ved either by the treatment with excess of diethyl- genic mixed diamondoidylaryl phosphines [15]. In this amine [19] or, more conveniently, using pyrrolidine paper we present the preparation of the secondary [20] under mild reaction conditions that retain the ab- diamondoid phosphines with the potential as ligands P-stereogenic center. in asymmetric catalysis. Experimental part solute configuration of the Results and discussion NMR spectra were recorded on a Bruker Avance III The aim of this work was to develop a prepara- 1 - tive method for the synthesis of chiral bulky phos- quencies for 13C and 31 spectrometer at 400 and 600 MHz (for H, the fre O H H P NMR are specifiedBH3 below) OH 1 P Cl P 1 P 1 R PCl2 1 LiAlH4 R BH3/THF R R F3CCOOH 2a,b 3ad (76%) 4ad (80%) 5ad (96%) 3bd (92%) 4bd (85%) 5bd (95%) 3ac (34%) 4ac (40%) 5ac (95%) 3bc (45%) 4bc (43%) 5bc (95%) a: 1-diamantyl c: R1 = , d: R1 = b: 4-diamantyl Scheme 2. The synthesis of borane complexes of 1- and 4-diamantyl-1-adamantyl phosphines and 1- and 4-diamantylphenyl phosphines 36 ISSN 2518-1548 (Online) Журнал органічної та фармацевтичної хімії. – 2020. – Т. 18, вип. 3 (71) ISSN 2308-8303 (Print) 1 13 31 with TMS ( 3PO4 ( P) as internal J = J = 31 1 J = P{ 3 H and C) and H (C−Р) 1.9 Hz), 43.8 (C, d, (C−Р)24 6034ClOP Hz), 45.7404.2036 (C, d, standards. High-resolution mass spectra (HRMS) were [M(C−Р)+]; found60 Hz).