molecules Review Microwaves as “Co-Catalysts” or as Substitute for Catalysts in Organophosphorus Chemistry György Keglevich Department of Organic Chemistry and Technology, Budapest University of Technology and Economics, 1521 Budapest, Hungary; [email protected] Abstract: The purpose of this review is to summarize the importance of microwave (MW) irradiation as a kind of catalyst in organophosphorus chemistry. Slow or reluctant reactions, such as the Diels-Alder cycloaddition or an inverse-Wittig type reaction, may be performed efficiently under MW irradiation. The direct esterification of phosphinic and phosphonic acids, which is practically impossible on conventional heating, may be realized under MW conditions. Ionic liquid additives may promote further esterifications. The opposite reaction, the hydrolysis of P-esters, has also relevance among the MW-assisted transformations. A typical case is when the catalysts are substituted by MWs, which is exemplified by the reduction of phosphine oxides, and by the Kabachnik–Fields condensation affording α-aminophosphonic derivatives. Finally, the Hirao P–C coupling reaction may serve as an example, when the catalyst may be simplified under MW conditions. All of the examples discussed fulfill the expectations of green chemistry. Keywords: microwave; organophosphorus chemistry; catalyst; catalyst- and solvent-free; green chemistry The spread of the microwave (MW) technique opened a new chapter in organic Citation: Keglevich, G. Microwaves chemistry in whole [1–3], and also in its specialized fields, such as heterocyclic [3–5] and as “Co-Catalysts” or as Substitute for organophosphorus chemistry [2,6]. MW irradiation makes possible more efficient syntheses Catalysts in Organophosphorus in terms of reaction time, selectivity, and purity [1,2]. The role of MWs in organic syntheses Chemistry. Molecules 2021, 26, 1196. provoked sharp disputes, however, today there is an agreement that thermal effects are https://doi.org/10.3390/ molecules26041196 responsible for the beneficial effect of MWs [7,8]. A widely accepted concept is that the efficiency of the MW irradiation is the consequence of the statistically occurring local Academic Editor: Cesar Mateo overheating in the bulk of the mixture [9–11]. During our work, we laid the stress on green chemical aspects within organophos- Received: 10 February 2021 phorus chemistry [12]. This will be summarized in this review article. Besides developing Accepted: 19 February 2021 efficient syntheses, we could enhance reluctant or slow reactions by applying the MW Published: 23 February 2021 irradiation (1). It was another option to promote further certain MW-assisted reactions by performing them in the presence of an ionic liquid additive/catalyst (2). It is another Publisher’s Note: MDPI stays neutral possibility to substitute certain catalysts by MW irradiation (3). Last but not least, MWs with regard to jurisdictional claims in may simplify catalytic systems/catalysts (4). In this paper, options (1)–(4) will be discussed published maps and institutional affil- in detail, placing the particular reactions into literature context. iations. 1. Microwave Irradiation Allowing the Inverse-Wittig Type Reaction That Is Reluctant on Conventional Heating The Diels–Alder reaction of 1-phenyl-1,2-dihydrophosphinine oxide 1 with dienophiles, Copyright: © 2021 by the author. like N-phenylmaleimide and dimethyl acetylenedicarboxylate (DMAD), resulted in the Licensee MDPI, Basel, Switzerland. formation of the respective phosphabicyclo[2.2.2]octene derivatives (2) and (3). The mi- This article is an open access article crowave (MW) technique was useful in shortening the reaction times and making the distributed under the terms and syntheses efficient. The MW-promoted reactions were 25 times faster than the thermal conditions of the Creative Commons variations (Scheme1)[13]. Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/). Molecules 2021, 26, 1196. https://doi.org/10.3390/molecules26041196 https://www.mdpi.com/journal/molecules Molecules 2021, 26, x FOR PEER REVIEW 2 of 24 Molecules 2021,, 26,, xx FORFOR PEERPEER REVIEWREVIEW 2 of 24 syntheses efficient. The MW-promoted reactions were 25 times faster than the thermal variations (Scheme 1) [13]. Molecules 2021, 26, 1196 2 of 23 syntheses efficient. The MW-promoted reactions were 25 times faster than the thermal variations (Scheme 1) [13]. Scheme 1. [4 + 2]Cycloadditions of a 1,2-dihydrophosphinine oxide (1) with dienophiles. However, the 1-(2,4,6-triisopropylphenyl-1,2-dihydrophosphinine) oxide (4) [14] un- SchemeSderwentcheme 1. an [4 + inverse 2]Cycloadditions 2]Cycloadditions-Wittig type of atransformation 1,2 1,2-dihydrophosphinine-dihydrophosphinine in reaction oxide with (1) with DMAD dienophiles. to afford the cor- responding β-oxophosphorane 5 (Scheme 2) [15,16]. However, the 1-(2,4,6-triisopropylphenyl-1,2-dihydrophosphinine)1-(2,4,6-triisopropylphenyl-1,2-dihydrophosphinine) oxide ( 4))[ [1144] un- derwent an an inverse inverse-Wittig-Wittig type type transformation transformation in inreaction reaction with with DMAD DMAD to afford to afford the cor- the correspondingresponding β-oxophosphoraneβ-oxophosphorane 5 (Scheme5 (Scheme 2) [12)[5,1156,].16 ]. Scheme 2. The inverse Wittig-type reaction of a P-aryl 1,2-dihydrohosphine oxide with dimethyl acetylenedicarboxylate (DMAD). SchemeSchemeThen, 2. TheThe the inverse inverse new protocol Wittig Wittig-type-type seemed reaction reaction to beof of aofa P P-aryla-aryl more 1,2 1,2-dihydrohosphine general-dihydro valuehosphine [17 oxide]. oxideThe with use with ofdimethyl dimethyl the MW acetylenedicarboxylatetechnique was advantageous (DMAD).(DMAD). not only in the inverse Wittig-type reaction of 2,4,6-triiso- propylphenyl-3-phospholene oxide but also in the reaction of 2,4,6-triiso- propylphenylphospholaneThen, the the new new protocol protocol seemedoxide seemed and to to be2,4,6 be of ofa- triisopropylphenylmore a more general general value value- 1,2[17-].dihydrophosphinine [17 The]. Theuse of use the of MW the MWtechniqueoxide technique (all representedwas advantageous was advantageous by formula not only6) not to affordin only thein inverseβ- theoxophosphoranes inverse Wittig Wittig-type-type reaction7 (Scheme reaction of 3)2,4,6 [1 of8-,1triiso- 2,4,6-9]. triisopropylphenyl-3-phospholenepropylphenylIn the novel-3-phospholen inverse Wittige oxide-type oxide reactions,but alsoalso inMW thein irradiation reactionthe reaction of made 2,4,6-triisopropylphenyl possibleof 2,4,6 reactions-triiso- phospholanepropylphenylphospholaneat 150 °C for 3 oxide h that and were 2,4,6-triisopropylphenyl-1,2-dihydrophosphinine ratheroxide reluctantand 2,4,6 on-triisopropylphenyl conventional heating.-1,2- dihydrophosphinineHence, oxide MW (all acted repre- as sentedoxidea kind (all byof catalyst.represented formula 6) to by afford formulaβ-oxophosphoranes 6) to afford β-oxophosphoranes7 (Scheme3)[18 7,19 (Scheme]. 3) [18,19]. In the novel inverse Wittig-type reactions, MW irradiation made possible reactions at 150 °C for 3 h that were rather reluctant on conventional heating. Hence, MW acted as a kind of catalyst. SchemeScheme 3.3. TheThe inverseinverse Wittig-typeWittig-type reactionreaction ofof P-arylP-aryl ringring phosphinephosphine oxidesoxides withwith DMAD.DMAD. InTheoretical the novel calculations inverse Wittig-type suggested reactions, a mechanism MW irradiation involving madean oxaphosphete possible reactions interme- at ◦ 150SdiatechemeC [20for 3., 21The 3]. h inverse that were Wittig rather-typereluctant reaction of on P-ary conventionall ring phosphine heating. oxides Hence, with DMAD. MW acted as a kindIn of catalyst.the above case, the nature of the 1,2-dihydrophosphinine oxide determined its re- activityTheoretical towards calculationsDMAD. Moreover, suggested both a mechanism the Diels–Alder involving cycloaddition an oxaphosphete and the interme- inverse- diate [20,,21].]. In the the above above case, case, the the nature nature of of the the 1,2 1,2-dihydrophosphinine-dihydrophosphinine oxide oxide determined determined its re- its reactivity towards DMAD. Moreover, both the Diels–Alder cycloaddition and the inverse- activity towards DMAD. Moreover, both the Diels–Alder cycloaddition and the inverse- Wittig type reaction took place efficiently on MW irradiation without the application of any catalyst. Molecules 2021, 26, x FOR PEER REVIEW 3 of 24 Molecules 2021, 26, 1196 Wittig type reaction took place efficiently on MW irradiation without the application3 of of 23 any catalyst. 2. Microwave Microwave-Assisted,-Assisted, Ionic Liquid Liquid-Catalyzed-Catalyzed Direct Esterification Esterification of P-OxoacidsP-Oxoacids TThathat I Iss Otherwise Impossi Impossibleble under Thermal Conditions PPhosphinichosphinic and and phosphonic acids cannot be involved in direct esterificationesterification under common conditions.conditions. OnlyOnly a a few few examples examples are are known known for for the the direct direct esterification esterification of P-acids. of P- acids.These reactionsThese reactions required required forcing conditionsforcing conditions and were and not were efficient not [ 22efficient–26]. However, [22–26]. itHow- was ever,found it bywas us found that the by P-acids us that canthe beP-acids esterified can be on esterified MW irradiation. on MW irradiation. The esterification esterification of 1 1-hydroxy-3-phospholene-hydroxy-3-phospholene oxide oxide ( (88)) with with a series of alcohols at 180180–235–235 °C◦C