Phosphine-Catalyzed Anti-Hydroboration

Letter Cite This: Org. Lett. 2018, 20, 1861−1865

pubs.acs.org/OrgLett

Phosphine-Catalyzed Anti-Hydroboration of Internal Alkynes Kazunori Nagao,† Ayaka Yamazaki,† Hirohisa Ohmiya,*,‡ and Masaya Sawamura*,† †

Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan Division of Pharmaceutical Sciences, Graduate School of Medical Sciences, Kanazawa University, Kakuma-machi, Kanazawa 920-1192, Japan

‡

S Supporting Information *

ABSTRACT: Trialkylphosphine organocatalysts have enabled regioselective anti-hydroboration of internal alkynes with pinacolborane reagents to provide (E)-disubstituted alkenylboronate compounds. The alkenylboronate can be used for derivatizations, such as protodeborylation, Suzuki−Miyaura coupling, conjugate reduction, and Diels−Alder reactions.

T

We report here a phosphine-catalyzed regioselective antihydroboration of internal alkynes, including alkynoates, alkynylamides, and 2-alkynylazoles, with easy-to-handle pinacolborane, which gives 1,2-disubstituted (E)-alkenylboronates (Scheme 1c).6 The regioselectivity of the hydroboration across the C−C triple bond exhibited inverse electronic demand, with the intrinsically electrophilic B atom being delivered to the positively charged β carbon atom of the alkynes. 1c,7 Accordingly, this class of alkenylboron compounds is difficult to access through other methods. The alkenylboronates can be used for various derivatizations, such as protodeborylation, Suzuki−Miyaura coupling, conjugate reduction, and Diels− Alder reactions. While phosphine-catalyzed anti-selective vicinal carboboration, silaboration, and diboration across the C−C triple bond in alkynoates have been established in our earlier work,8 extension of the concept toward anti-selective hydroboration faces nontrivial challenges, such as the use of easy-to-handle pinacolborane, the expansion of a substrate scope for alkynes, and a diverse derivatization of 1,2-disubstituted (E)-alkenylboronate products. Our screening of phosphine catalysts for the reaction between pinacolborane (1) and 3-phenylpropiolate (2a) identified PBu3 to be the most effective (see Table 1). Thus, the reaction between 1 (0.3 mmol) and 2a (0.3 mmol) in the presence of PBu3 (2.5 mol %) in THF at 60 °C over 3 h gave βboryl acrylate 3a in 92% isolated yield (based on 2a; 99% NMR yield; complete conversion of 2a) (eq 1). The H−B bond

he hydroboration of alkynes is a useful method for the synthesis of alkenylborons, which are versatile synthetic intermediates.1,2 Typically, the H−B bond addition across the C−C triple bond occurs with syn stereochemistry via a fourmembered transition state. Accordingly, anti-selective hydroboration of alkynes is an important challenge in modern organic synthesis.3,4 More specifically, anti-hydroboration of internal alkynes to prepare 1,2-disubstituted (E)-configured alkenylboron compounds has been a subject of more recent studies.5 For instance, Fürstner and co-worker developed a [Cp*Ru(MeCN)3]PF6-catalyzed anti-hydroboration of internal alkynes with pinacolborane, while the reaction of unsymmetrical alkynes was not regioselective (Scheme 1a).5a Shi and Scheme 1. Anti-Hydroboration of Internal Alkynes

co-workers reported the intramolecular anti-hydroboration across C−C triple bonds in propargyl amine boranecarbonitriles with a triazole−Au complex catalyst (Scheme 1a).5b Recently, Liu and co-workers reported anti-hydroboration of internal 1,3-eneyne using a 1,4-azaborine−Pd complex (Scheme 1a).5c Wang and co-workers reported the anti-hydroboration of 2-pyridyl alkynes with 9-borabicyclo[3.3.1]nonane (9-BBN-H) (Scheme 1b).5d © 2018 American Chemical Society

addition was completely regioselective and anti-stereoselective under these conditions. The B atom in 3a had no interaction Received: February 2, 2018 Published: March 8, 2018 1861

DOI: 10.1021/acs.orglett.8b00390 Org. Lett. 2018, 20, 1861−1865

Letter

Organic Letters Table 1. Catalyst Effects in Reaction between 1 and 2aa

entry

catalyst

yield (%) of 3ab

anti/syn of 3ac

yield (%) of 4ab

1 2 3 4 5 6 7 8

PBu3 PMe3 PPhMe2 PPh2Me PPh3 PCy3 PtBu3 none

99 93 93 56 0 87 0 0

>99:1 >99:1 96:4 77:23 − 93:7 − −

0 7 7 0 − 0 − −

Table 2. Anti-Hydroboration of β-Aryl-Substituted Alkynoatesa

a Reactions were carried out with 1 (0.3 mmol), 2a (0.3 mmol), and phosphine (10 mol %) in THF (0.6 mL) at 60 °C for 4 h. b1H NMR yield. cDetermined by 1H NMR analysis of the crude product.

with the carbonyl oxygen, as indicated by 11B NMR spectroscopy. The hydroboration also occurred efficiently without a solvent under catalysis of PBu3 (2.5 mol %), giving 3a in 92% yield. The reaction was scalable: a gram-scale reaction with 1.74 g (10 mmol) of 2a and 1.27 g (10 mmol) of 1 in the presence of PBu3 (2.5 mol %) at 60 °C over 12 h afforded 3a in 76% isolated yield. The effect of phosphine catalysts on the reaction between 1 and 2a are shown in Table 1. PMe3 was also effective, but a small amount of protodeborylation product, trans ethyl cinnamate (4a), was observed (entry 2). The use of PPhMe2 slightly decreased the anti-selectivity with 7% formation of 4a (entry 3). PPh2Me resulted in significantly decreased product yield and anti-selectivity (entry 4). A weaker electron-donor PPh3 was not effective (entry 5). The effects of bulkier trialkylphosphine PCy3 were comparable with those of PPh2Me in terms of both product yield and anti selectivity (entry 6). However, the sterically more demanding PtBu3 induced no reaction (entry 7). The reaction did not occur in the absence of a phosphine (entry 8). The protocol with a PBu3 catalyst was applicable to various β-aryl-substituted alkynoates (Table 2).8 Methoxy, fluoro, bromo, 2-(dimethylamino)ethoxy, ketone, and ester groups were tolerated at the para- or meta-positions of the β-aryl substituent (entries 1−6). A bulky o-tolyl substituent also gave the efficient product yield by using 20 mol % of catalyst (entry 7, 5 mol %: 37%). 2-Furyl- or 2-thienyl-substituted alkynoates (2i, j) underwent the anti-hydroboration (entries 8 and 9). The lower yield of 3i was due to the decomposition of 2i in the reaction conditions. Unfortunately, this hydroboration could not tolerate the 2-pyridyl-substituted alkynoate (data not shown). This trend is consistent with relatively low yield of 3d (enrty 3). The reaction of 2-naphthyl-substituted alkynoate 2k gave 94% anti selectivity (entry 10). The hydroboration of 1,3-enyne 2l afforded the corresponding 2,4-dienylboronate 3l with the alkene moiety untouched (entry 11). Results with β-alkyl-substituted alkynoates are summarized in Table 3. The reaction of 2-pentynoate (2m) under the conditions optimized for 2a (eq 1: 10 mol % PBu3, THF, 60 °C) occurred with only moderate anti selectivity (anti/syn 71:29) (entry 1). The use of PMe3 instead of PBu3 improved the anti selectivity to 89% (entry 2). Further improvement in

a

Reactions were carried out with 1 (0.3 mmol), 2 (0.3 mmol), and PBu3 (2.5 mol %; entries 1, 2, 4, 8, 9; 5 mol %; entry 3; 7.5 mol %; entries 5, 6; 10 mol %; entries 10, 11, 20 mol %; entry 7) in THF (50 μL; entries 2−7, 10, 11; neat; 1, 8, 9) at 60 °C for 4 h. bYield of the isolated product. cDetermined by 1H NMR analysis of the crude product. d4g was obtained in 19% yield. eThe isolated product was contaminated with a trace of unidentified material. f76% 1H NMR yield. The product was significantly decomposed during silica gel chromatography.

yield and stereoselectivity were made by decreasing the reaction temperature to room temperature, giving 3m in 89% yield with an anti/syn ratio as high as 96:4 (entry 3). Thus, the reactions of other β-alkyl-substituted alkynoates were conducted with PMe3 (10 mol %) at room temperature (entries 4−9). The reaction of the alkynoate (2n, o) having a Me or cyclopropyl group at the β-position also proceeded with high anti selectivities (entries 4 and 5). However, the alkynoate 2p having a cyclohexyl group at the β-position reacted with poor stereoselectivity (entry 6). Although the decomposition of substrate 2q was observed in the reaction conditions, the hydroboration product 3q was obtained in moderate yield (entry 7). Alkynoates (2r, s) having THP or TBDMS ether moieties at the terminal of the aliphatic chain were compatible with the anti-hydroboration (entries 8 and 9). β-Silylated alkynoates were also examined, but did not give reasonable product yields under tested conditions (data not shown). Applicability of the phosphine-catalyzed anti-hydroboration was not limited to reactions with the alkynoates, but could be extended to alkynylamides or 2-alkynylazoles (Table 4).9 Notably, the previous phosphine-catalyzed carboboration, silaboration, and diboration were limited to the use of alkynoates as alkynic substrates.8 The reaction of N,Ndimethylamide (5a) or N-methyl-N-phenylamide (5b) with a PBu3 catalyst furnished the corresponding β-borylacrylamides with complete anti selectivity (entries 1 and 2). In this case, MeCN was the appropriate solvent, instead of THF in terms of 1862


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Organic Letters Table 3. Anti-Hydroboration of β-Alkyl-Substituted Alkynoatesa

Table 4. Anti-Hydroboration of Alkynylamides or 2Alkynylazolesa

a

Reactions were carried out with 1 (0.3 mmol), 2 (0.3 mmol), and PMe3 (10 mol %) in THF at 25 °C for 12 h unless otherwise noted. b Yield of the isolated product. cDetermined by 1H NMR analysis of the crude product. d60 °C, 4 h. f1 (0.45 mmol) was used. g24 h.

a

Entries 1 and 2: Reactions were carried out with 1 (0.3 mmol), 5 (0.3 mmol), and PBu3 (2.5 mol %) in MeCN at 60 °C for 12 h. Entries 3− 6: Reactions were carried out with 1 (0.3 mmol), 7 (0.3 mmol), and PMe3 (20 mol %) in MeCN at 60 °C for 24 h. bYield of the isolated product. cDetermined by 1H NMR analysis of the crude product.

the product yield. The 11B NMR spectra of 6a and 6b indicated carbonyl-to-boron coordination. However, employing the alkynes having primary and secondary amides resulted in low conversions (data not shown). The reaction of 2-alkynylbenzoxazole (7a) with 1 in the presence of PMe3 (10 mol %) in MeCN at 60 °C proceeded efficiently over 24 h, giving the corresponding alkenylboronate 8a with the exceptional anti selectivity (entry 3). PMe3 was better than PBu3 as a catalyst in terms of the product yield. The boron atom of 8a has no interaction with the azole nitrogen, as indicated by 11B NMR spectroscopy. Benzothiazole, benzoimidazole, and pyrimidine were also tolerated as azole groups in the PMe3-catalyzed reaction (entries 4−6). A possible catalytic cycle for the hydroboration is illustrated in Figure 1. As proposed for the phosphine-catalyzed carboboration, silaboration, and diboration of alkynoates,8 the catalytic cycle begins with the conjugate addition of the phosphine to the electron-deficient alkyne with the assistance of Lewis acidic activation of the carbonyl or azole groups by 1 through coordination with the oxygen or nitrogen atoms, respectively, to form a zwitterionic intermediate (A). The hydride in A migrates to the sp-hybridized central carbon of the allene moiety to form ylide intermediates (B1/B2). Next, the ylide carbon of B2 attacks the proximal B atom to form cyclic borate C1. Finally, elimination of the phosphine associated with B−X cleavage affords the hydroboration product. The B−X interaction in C1 and the concerted nature of the final elimination step is responsible for the anti stereochemistry of the hydroboration.

Figure 1. A possible catalytic cycle.

The minor occurrence of syn-hydroboration with bulky phosphines, such as PPhMe2, PPh2Me, and PCy3 suggests that the B−X interaction in C1 becomes less favorable due to the steric repulsion between the phosphine and the pinacol moiety (see Table 1).10 As a result, a nonselective elimination reaction of C2 affords anti/syn mixtures.11 Based on this consideration, the reduced antiselectivity with the β-alkyl substituent in the alkynoate in comparison with the β-aryl substituent may be due to reduced Lewis acidity of the boron atom (see Table 3). This consideration is consistent with the better anti-selectivity with 1863


Letter

Organic Letters the less electron-donating β-cyclopropyl substituent (Table 3, entry 5). The (E)-alkenylboronates obtained by the phosphinecatalyzed anti-hydroboration was used to demonstrate their synthetic utility (eqs 2−4). For example, protodeborylation of β-boryl acrylate 3a with AgF gave (E)-ethyl cinnamate (4a) (eq 2).5a

handle pinacolborane to produce 1,2-disubstituted (E)alkenylboronates. The H−B bond addition across the polar C−C triple bond occurred with inverse electronic demand with regard to the regioselectivity, with the intrinsically electrophilic B atom being delivered to the positively charged β carbon atom. The alkenylboronate derivatives underwent various molecular transformations, such as protodeborylation, Suzuki−Miyaura coupling, conjugate reduction, and intramolecular Diels−Alder reactions. Thus, the phosphine-catalyzed protocol allows straightforward and efficient synthesis of 1,2-disubstituted (E)-alkenylboronates, which are versatile building blocks for organic synthesis.

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ASSOCIATED CONTENT

* Supporting Information S

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.8b00390. Experimental details and characterization data for all new compounds (PDF)

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In contrast to the inertness of the 9-BBN-type-β-boryl acrylate obtained by the phosphine-catalyzed anti-carboboration toward Suzuki−Miyaura coupling,8 the organoboronate 3a underwent Pd-catalyzed coupling with 4-bromoanisole to afford β-diaryl acrylate 9a in excellent yield and Z-selectivity. Next, conjugate reduction of 3a with poly(methylhydrosiloxane) (PMHS) to prepare an secondary alkylboronate was investigated (eq 4). As a result, N-heterocyclic carbene (NHC) ligand IPr was effective for conjugate reduction of 3a, in accordance with our earlier findings on the copper-catalyzed conjugate reduction of β,β-diboryl acrylates with PMHS.12 The anti-hydroboration of alkynoates and subsequent intramolecular Diels−Alder reaction allowed the stereoselective synthesis of trans-fused bicyclic γ-lactone derivatives with a tertiary alkylboronate moiety (eqs 5−7).13 For example, the

AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Hirohisa Ohmiya: 0000-0002-1374-1137 Masaya Sawamura: 0000-0002-8770-2982 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS This work was supported by Grants-in-Aid for Scientific Research (B) (No. 15H03803), JSPS, to H.O., and by CREST, JST, to M.S. Additionally, K.N. thanks JSPS for scholarship support.

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REFERENCES

(1) For pioneering works on hydroboration of alkynes, see: (a) Brown, H. C.; Zweifel, G. J. Am. Chem. Soc. 1961, 83, 3834. (b) Brown, H. C.; Gupta, S. K. J. Am. Chem. Soc. 1972, 94, 4370. (c) Plamondon, J.; Snow, J. T.; Zweifel, G. Organometal. Chem. Syn. 1971, 1, 249. (d) Tucker, C. E.; Davidson, J.; Knochel, P. J. Org. Chem. 1992, 57, 3482. (2) For reviews on hydroboration of alkynes, see: (a) Beletskaya, I.; Pelter, A. Tetrahedron 1997, 53, 4957. (b) Trost, B. M.; Ball, Z. T. Synthesis 2005, 2005, 853. (c) Barbeyron, R.; Benedetti, E.; Cossy, J.; Vasseur, J.; Arseniyadis, S.; Smietana, M. Tetrahedron 2014, 70, 8431. (3) For transition-metal-catalyzed hydroboration of terminal alkynes to prepare (Z)-alkenylboron compounds (formal anti-hydroboration), see: (a) Ohmura, T.; Yamamoto, Y.; Miyaura, N. J. Am. Chem. Soc. 2000, 122, 4990. (b) Gunanathan, C.; Hölscher, M. M.; Pan, F.; Leitner, W. J. Am. Chem. Soc. 2012, 134, 14349. (c) Cid, J.; Carbó, J. J.; Fernández, E. Chem. - Eur. J. 2012, 18, 1512. (d) Obligacion, J. V.; Neely, J. M.; Yazdani, A. N.; Pappas, I.; Chirik, P. J. J. Am. Chem. Soc. 2015, 137, 5855. (4) For catalytic anti-hydroboration of terminal alkynes, see: (a) Jang, W. J.; Lee, W. L.; Moon, J. H.; Lee, J. Y.; Yun, J. Org. Lett. 2016, 18, 1390. (b) McGough, J. S.; Butler, S. M.; Cade, I. A.; Ingleson, M. J. Chem. Sci. 2016, 7, 3384. (5) (a) Sundararaju, B.; Fürstner, A. Angew. Chem., Int. Ed. 2013, 52, 14050. (b) Wang, Q.; Motika, S. E.; Akhmedov, N. G.; Petersen, J. L.;

alkynoate 3t bearing a diene moiety underwent anti-hydroboration. The succeeding intramolecular Diels−Alder reaction produced bicyclic lactone 11t with excellent exo-selectivity (eq 5). The protocol was also applicable to the stereoselective synthesis of the 2,3-fused furan or indole derivatives (11u, v) (eqs 6 and 7). In summary, we have developed phosphine-catalyzed regioselective anti-hydroboration of internal alkynes, including alkynoates, alkynylamides, and 2-alkynylazoles with easy-to1864


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Organic Letters Shi, X. Angew. Chem., Int. Ed. 2014, 53, 5418. (c) Xu, S.; Zhang, Y.; Li, Bo.; Liu, S.-Y. J. Am. Chem. Soc. 2016, 138, 14566. (d) Yuan, K.; Suzuki, N.; Mellerup, S. K.; Wang, X.; Yamaguchi, S.; Wang, S. Org. Lett. 2016, 18, 720. (6) For organocatalytic syn-hydroboration of alkynes, see: (a) Wen, K.; Chen, J.; Gao, F.; Bhadury, P. S.; Fan, E.; Sun, Z. Org. Biomol. Chem. 2013, 11, 6350. (b) Ho, H. E.; Asao, N.; Yamamoto, Y.; Jin, T. Org. Lett. 2014, 16, 4670. (7) For Cu-catalyzed syn-hydroboration of alkynoates, see: (a) Lipshutz, B. H.; Boškovic, Ž . V.; Aue, D. H. Angew. Chem., Int. Ed. 2008, 47, 10183. (b) Semba, K.; Fujihara, T.; Terao, J.; Tsuji, Y. Chem. - Eur. J. 2012, 18, 4179. (c) Lee, J.-E.; Kwon, J.; Yun, J. Chem. Commun. 2008, 733. (8) (a) Nagao, K.; Ohmiya, H.; Sawamura, M. J. Am. Chem. Soc. 2014, 136, 10605. (b) Nagao, K.; Ohmiya, H.; Sawamura, M. Org. Lett. 2015, 17, 1304. (c) Yamazaki, A.; Nagao, K.; Ohmiya, H.; Sawamura, M. Angew. Chem., Int. Ed. 2018, DOI: 10.1002/anie.201712351. (9) As alkynic substrates, the corresponding conjugated aldehydes and ketones showed no reactivity under similar conditions. The reaction of propiolate afforded a complex mixture with no hydroboration product. (10) The subjection of isomerically pure anti-3m or syn-3m to the standard reaction conditions resulted in no reaction. (11) Ohmura, T.; Morimasa, Y.; Suginome, M. Chem. Lett. 2017, 46, 1793. (12) Morinaga, A.; Nagao, K.; Ohmiya, H.; Sawamura, M. Angew. Chem., Int. Ed. 2015, 54, 15859. (13) (a) Lorvelec, G.; Vaultier, M. Tetrahedron Lett. 1998, 39, 5185. (b) Hilt, G.; Bolze, P. Synthesis 2005, 2005, 2091.

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Phosphine-Catalyzed Anti-Hydroboration

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