Boron Lewis Acid Catalyzed Hydrophosphorylation of N-Heteroaryl-Substituted Alkenes

Abstract

The hydrophosphorylation of N-heteroaryl-substituted alkenes catalyzed by a boron Lewis acid catalyst is reported. This reaction occurs with a range of alkenes bearing N-heterocycles, including pyridines, a quinoline, a pyrrole, and a benzothiazole, resulting in the production of β-N-heteroaryl alkylphosphonates in good yields under additive-free, operationally simple conditions. The mechanistic insights suggest that this hydrophosphorylation involves the deprotonation of the P–H bond of dialkyl phosphites, enabled by the cooperative effects of a boron acid and the basic N-heterocyclic moiety of the alkenes. The resulting phosphonate anion serves as an effective phosphorus nucleophile for the conjugate addition to the concurrently formed N-protonated alkenes. These β-N-heteroaryl alkylphosphonates can be further converted into other valuable organophosphorus compounds through the introduction of an alcohol group or the reduction of the phosphine oxide moiety.

Key words

main-group chemistry - organophosphorus compounds - carbon–phosphorus bond - cooperative deprotonation

Publication History

Received: 23 October 2023

Accepted after revision: 28 November 2023

Accepted Manuscript online:
28 November 2023

Article published online:
02 January 2024

• References


For selected examples of the usefulness of β-pyridyl phosphines, see:
• 1a Krečmerová M, Majer P, Rais R, Slusher BS. Front. Chem. 2022; 10: 889737
• 1b Heidel KM, Dowd CS. Future Med. Chem. 2019; 11: 1625
• 1c Chen L, Zou Y.-X. Org. Biomol. Chem. 2018; 16: 7544
• 1d Deng L, Dio J, Chen P, Pujari V, Yao Y, Cheng G, Crick DC, Prasad BV. V, Song Y. J. Med. Chem. 2011; 54: 4721

For selected examples of P,N-ligands, see:
• 2a Rong MK, Holtrop F, Slootweg JC, Lammertsma K. Coord. Chem. Rev. 2019; 380: 1
• 2b Rokade BV, Guiry PJ. ACS Catal. 2018; 8: 624
• 2c Carroll MP, Guiry PJ. Chem. Soc. Rev. 2014; 43: 819
• 2d Chen S, Ng JK.-P, Pullarkat SA, Liu F, Li Y, Leung P.-H. Organometallics 2010; 29: 3374
• 2e Bunlaksananusorn T, Knochel P. Angew. Chem. Int. Ed. 2003; 42: 3941
• 2f Kwong FY, Yang Q, Mak TC. W, Chan AS. C, Chan KS. J. Org. Chem. 2002; 67: 2769
• 2g Loiseleur O, Hayashi M, Keenan M, Schmees N, Pfaltz A. J. Organomet. Chem. 1999; 576: 16

For selected examples of conversion to other useful β-N-heteroaryl alkylphosphines, see:
• 3a Ash J, Huang H, Cordero P, Kang JY. Org. Biomol. Chem. 2021; 19: 6007
• 3b Kendall AJ, Salazar CA, Martino PF, Tyler DR. Organometallics 2014; 33: 6171
• 3c Demmer CS, Krogsgaard-Larsen N, Bunch L. Chem. Rev. 2011; 111: 7981

For examples of the synthesis of β-N-heteroaryl alkylphosphonates, see:
• 4a Xu C.-H, Xiong Z.-Q, Li Y, Zhu Y.-P, Li J.-H. Org. Chem. Front. 2022; 9: 476
• 4b Buquoi JQ, Lear JM, Gu X, Nagib DA. ACS Catal. 2019; 9: 5330
• 4c He Y.-T, Won J, Kim J, Park B, Kim T, Baik M.-H, Hong S. Org. Chem. Front. 2018; 5: 2595
• 5 Trost BM. Science 1991; 254: 1471

For selective reviews of hydrophosphorylation, see:
• 6a Rulev AY. RSC Adv. 2014; 4: 26002
• 6b Zhao D, Wang R. Chem. Soc. Rev. 2012; 41: 2095

For selected examples and reviews of tautomerization of SPOs, see:
• 7a Gallen A, Riera A, Verdaguer X, Grabulosa A. Catal. Sci. Technol. 2019; 9: 5504
• 7b Janesko BG, Fisher HC, Bridle MJ, Montchamp J.-L. J. Org. Chem. 2015; 80: 10025

For selected examples of cooperative deprotonation of H-phosphonates by acid/base catalysis, see:
• 8a Kwak S, Choi J, Han J, Lee SY. ACS Catal. 2022; 12: 212
• 8b Li J, Gao Z, Guo Y, Liu H, Zhao P, Bi X, Shi E, Xiao J. RSC. Adv. 2022; 12: 18889
• 8c Liu Y, Fan X, Li ZH, Wang H. Chem. Commun. 2017; 53: 10890

For selected examples of cooperative deprotonation of other pronucleophiles, see:
• 9a Zhao C, Wang Y, Pham Q, Dai C, Chatterjee A, Wasa M. J. Am. Chem. Soc. 2023; 145: 14233
• 9b Yang Q, Zhou J, Wang J. Chem. Sci. 2023; 14: 4413
• 9c Tian J.-J, Liu N, Liu Q.-F, Sun W, Wang X.-C. J. Am. Chem. Soc. 2021; 143: 3054
• 9d Cao M, Yesilcimen A, Wasa M. J. Am. Chem. Soc. 2019; 141: 4199
• 9e Shang M, Cao M, Wang Q, Wasa M. Angew. Chem. Int. Ed. 2017; 56: 13338
• 10 For the pK _a value of organophosphorus compounds, see: Li J.-N, Liu L, Fu Y, Guo Q.-X. Tetrahedron 2006; 62: 4453

For selected reviews of frustrated Lewis pairs, see:
• 11a Stephan DW. J. Am. Chem. Soc. 2021; 143: 20002
• 11b Stephan DW. J. Am. Chem. Soc. 2015; 137: 10018
• 12 For the boron Lewis acid catalyzed P–H addition of diarylphosphine oxides to N-heteroaryl-substituted alkenes, see: Han J, Kim J, Lee J, Kim Y, Lee SY. J. Org. Chem. 2020; 85: 15476

For selected examples of synthetic utilities and biological applications of α-hydroxyphosphonates, see:
• 13a Varga PR, Belovics A, Bagi P, Tóth S, Szakács G, Bősze S, Szabó R, Drahos L, Keglevich G. Molecules 2022; 27: 2067
• 13b Rádai Z. Phosphorus Sulfur Silicon Relat. Elem. 2019; 194: 425
• 13c Rádai Z, Keglevich G. Molecules 2018; 23: 1493
• 13d Chakrabarty S, Trakacs JM. ACS Catal. 2018; 8: 10530

For selected examples of reduction of tertiary phosphine oxides, see:
• 14a Yamada M, Goto M, Yamano M. Tetrahedron Lett. 2021; 67: 152837
• 14b Merle N, Kociok-Köhn G, Mahon MF, Frost CG, Ruggerio GD, Weller AS, Willis MC. Dalton Trans. 2004; 3883
• 14c Jaska CA, Dorn H, Lough AJ, Manners I. Chem. Eur. J. 2003; 9: 271
• 14d Volkov O, Macías R, Rath NP, Barton L. Inorg. Chem. 2002; 41: 5837

For selected examples of deprotection procedures of phosphine-borane complexes, see:
• 15a Demchuk OM, Jasinski R, Strzelecka D, Dziuba K, Kula K, Chrzanowski J, Krasowska D. Pure Appl. Chem. 2018; 90: 49
• 15b Sayalero S, Pericàs MA. Synlett 2006; 2585
• 15c Schröder M, Nozaki K, Hiyama T. Bull. Chem. Soc. Jpn. 2004; 77: 1931

For synthetic methods of 1,1-disubstituted pyridyl alkenes from ketones (Wittig reaction), see:
• 16a Wang J, Shao B, Ge H, Li Y, Qi H, Xiao L. Org. Lett. 2023; 25: 5333
• 16b Fu S, Wang L, Dong H, Yu J, Xu L, Xiao J. Tetrahedron Lett. 2016; 62: 4533
• 16c Li Y, Guo F, Zha Z, Wang Z. Chem. Asian J. 2013; 8: 534