3.4 Catalysis with Mixed Adamantyl and tert-Butyl substituted Diphosphines
3.4.1 Diphosphine Ligand Syntheses
In order to synthesize mixed Ad-tBu-diphosphines several possible routes are available as is known from the literature.[75,76,77,78] The synthetic strategy towards the diphosphine 90 starts with the formation of phosphine borane 87 as important precursor complex (Scheme 41).
Scheme 41. Retrosynthetic consideration on diphosphine 90.
First attempts to synthesize 87 were not successful due to purification problems and for stability reasons of certain intermediates (Scheme 42). Intermediate 85 can be synthesized starting from adamantane 83 with a mixture of PCl3/AlCl3 (i).[75] In our hands, unfortunately, a mixture of mono- and dialkylated phosphinoyl derivatives were generated, which could hardly be separated causing a significant loss in yield. As expected, the treatment of 1-bromoadamantane 84 with PCl3 and AlBr3 (ii) led to complex mixtures of compounds. Therefore, this synthesis was not pursued further.[75d] Finally, commercially available 1-bromoadamantane 84 was converted to 1-adamantyl-phosphonic-dichloride 85 by the reaction of PCl3 in H2SO4 at 0°C followed by hydrolysis (iii).[75a]
After two recrystallizations from acetone the pure product was obtained as white crystals in moderate yield of 41 %.
Scheme 42. Possible route to monophosphine 87.[28c, 75]
In a patent application of Lucite International[28c] the synthesis of a series of alkyl-substituted adamantyl phosphine ligands including phosphine 87 is described following the route outlined in Scheme 42. Despite several attempts, however, the final step (86-87) was not successful in our
hands and only monophosphine 86 could be isolated under varying reaction conditions. For 86 neither yield, nor corresponding required analytical proof for phosphine 87 were published in the mentioned patent.
Finally, the synthetic route outlined in Scheme 43 led to the desired phosphine 87 and subsequently to diphosphines rac-90 and meso-90. After 1-bromoadamantane 84 had been converted to compound 85, further reaction of 85 with tert-BuLi followed by aqueous work-up delivered the secondary phosphine oxide 88 in high yield.[76] For the reduction of the phosphine oxide 88 a broad selection of reagents such as metal hydrides (e.g. LiAlH4, DIBAL) or silanes (e.g. HSiCl3) are generally available but quite often harsh reaction conditions are required. In short, we found a method to reduce the phosphine oxide to the secondary phosphine with simultaneous borane protection. The use of BH3·SMe2 enables the efficient transformation of secondary phosphine oxides to phosphine-boranes under mild conditions in high yields.[79] In the present case, the phosphine oxide 88 was dissolved in THF and treated with a solution of BH3·SMe2 complex in THF and water. After 2 hours reaction time at room temperature the reaction suspension was filtered from the resulting solid boric acid.
After evaporation of the filtrate, the desired phosphine-borane 87 is formed as white solid, which could be directly used in the next step. It should be noted that the quantities of the added BH3·SMe2
complex were significantly reduced compared to the literature example[79] which describes the addition of 20 equivalents of BH3·SMe2 to achieve sufficient results. In the present example (step from 88 to 87) only 5 equivalents were required to generate the phosphine-borane 87 in yield better than 80 %.
Borane-phosphine 87 could be lithiated by treatment with n-BuLi at -80 °C followed by adding
'-dichloroxylene to give the corresponding borane-diphosphine complex 89 (63 %) as diastereomeric mixture (rac- and meso-isomer).
Scheme 43. Synthetic route to diphosphines rac-90 and meso-90.
Surprisingly, the diastereoisomeric mixture could be easily separated by several washes with methylene chloride leading to solid rac-89, which has a very poor solubility in methylene chloride as compared to its diastereomer meso-89, which turned out to be be readily soluble in methylene chloride. The separated isomeric borane-diphosphines were each deprotected by treatment with HBF4·OEt2 to obtain the protonated diphosphine ligands as colorless BF4 salts. Neutralization by simple extraction with aqueous saturated bicarbonate solution afforded the neutral ligands rac-90 and meso-90.
It was proved by NMR analysis, that the crude reaction mixture (mix-90) consisted of diasteromeric compounds. Figure 25 illustrates differences of chemical shifts in the 1H NMR and 31P{1H} NMR spectra of both separated stereoisomers (see especially the chemical shifts of protons CH2Ph of rac and meso as well as of phosphorus nucleus, details in Exp. Section). In the 13C{1H} NMR spectra nearly all signals of the stereoisomeric mixture mix-90 are doubled.
Figure 25. 1H NMR and 31P{1H} NMR sections of isomeric mixture mixture mix-90, pure compounds rac-90 as well as meso-90.
First attempts[80,81,82] for the synthesis of the diphosphine 100 followed the reaction schemes outlined in Scheme 44 and 45. The selective mono-chlorination of the diol 91 succeeded in high yield with concentrated hydrogenchloride in toluene solution to give 92.[80] Compound 92 was further reacted to 93 in the presence of 1 equiv. of mesyl chloride.[81] After aqueous extraction and evaporation of methylene chloride compound 93 was activated towards selective mono-substitution by adding 1 equiv. of Li[Ad2PBH3] (43) at -80 °C. Due to the weaker activity of the chloride versus the mesyl group under given conditions the substitution should proceed preferably at the carbon atom of the mesylated hydroxyl group. In the next step the chloride should be substituted by Li[tBu2PBH3] (95). Unfortunately, this procedure proved to be difficult, because the substitution reaction step from compound 93 to 94 proceeds unselectively and leads to mixtures of phosphine 94 and tetra-adamantyl diphosphine 73.
Scheme 44. First approacht to 96.
Another approach pursueds the selective substitution of '-dichloroxylene (72) in two steps, first with Li[Ad2PBH3] (43), followed by Li[PtBu2BH3] (95), at low temperatures of -60 °C and -80°C, respectively, in order to control the selectively as well as possible (Scheme 45). Unfortunately, only a 1:1 mixture of the desired mono-substituted benzyl phosphine 94 and tetra-adamantyl phosphine 73 was obtained after sublimation of the unreacted starting material 72 in 54 % yield in the first reaction step (i).
Scheme 45. Second approach to 96.
Eventually, the reaction sequence outlined in Scheme 46 led to the desired diphosphine 100.
Starting with dibenzyl-alcohol 91, which was reacted with thionyl chloride to give the seven-membered cyclic sulfite 97, followed by oxidation with NaIO4 and RuCl3 x H2O yielded the cyclic sulfate 98 after crystallization from THF/hexane at -20 °C.[83] Treatment of 98 with one equiv. of in-situ generated Li[PAd2 BH3] (43) led to ring-opening to afford the mono-substituted borane-phosphine 99 as a lithium salt in solution. The borane protection of monoborane-phosphine 99 is essential to avoid the intramolecular ring closure reaction forming a stable cyclic phosphine (five-membered phosphine ring). For the second substitution of the remaining primary sulfate 99 (poor leaving group) in-situ generated Li[PtBu2 BH3] (1 equiv. of 95) was added at room temperature to the reaction solution of 99 (formation monitored by 31P{1H} NMR) and furnished borane-proteced diphosphine 96 in high yield. The final deprotection of the borane groups was achieved by treatment of 96 with HBF4·OEt2 to give the desired mixed diphosphine 100.
Scheme 46. Synthesis of diphosphine 100.
The addition of monophosphine boranes 43 and 95 to the reaction solution of 98 in reversed order (first 95 than 43) was not satisfactory and gave mixtures of substituted phosphines as identified by NMR measurements. Possible reasons are the lower reactivity of Li[PAd2BH3] (43) as compared to Li[PtBu2BH3] (95) in combination with weak leaving group properties of the remaining charged sulfate group. According to the literature phosphine substitution of 98 is generally described at -80°C reaction temperature, which did not work in the present case and thus, the reaction was conducted at increased temperatures of 20 °C.[83]