Stereoselective Syntheses of γ-Boryl Substituted syn-β-Alkoxy- and

Letter Cite This: Org. Lett. 2019, 21, 4638−4641

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Stereoselective Syntheses of γ‑Boryl Substituted syn-β-Alkoxy- and syn-β-Amino-homoallylic Alcohols via a Regio- and Stereoselective Allene Diboration and Aldehyde Allylboration Reaction Sequence Jichao Chen, Shang Gao, John D. Gorden, and Ming Chen* Department of Chemistry and Biochemistry, Auburn University, Auburn, Alabama 36849, United States

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ABSTRACT: Diastereoselective synthesis of γ-boryl substituted syn-β-alkoxy- or syn-β-amino-homoallylic alcohols is developed. Pt-catalyzed regioselective diboration of alkoxyallene or aminoallene with B2pin2 occurred at the terminal alkene unit of the allene to give (Z)-γ-alkoxy- or (Z)-γ-amino-β-boryl substituted allylboronates with high selectivities. Addition of the allylboronates to aldehydes followed by protection of the resulting secondary hydroxyl group gave TES-protected syn-1,2diols and syn-1,2-amino alcohols with high diastereoselectivities. The vinyl-Bpin group in the products is a useful handle for further transformations. boronate precursor A (eq 1, Scheme 1).8 However, only one aldehyde substrate was reported in the reaction with reagent B to give syn-adduct in moderate yield. The development of (Z)-γamino-β-boryl substituted reagents 2 that react with a broad scope of aldehyde substrates is therefore highly valuable. More recently, the Murakami group reported a highly E-selective olefin isomerization approach using a Ru catalyst to access (E)γ-alkoxy-β-boryl-substituted allylboronate D from vinyl boronate precursor C. Allylboration of aldehydes with reagent D afforded anti-homoallylic alcohol products with high diastereoselectivities (eq 2, Scheme 1).9 The method that permits stereoselective syntheses of the syn-isomers, however, is still not available. With our continuing efforts to develop novel allylation reagents for chemical synthesis,10 we report herein stereoselective synthesis of (Z)-γ-alkoxy- or (Z)-γ-amino-β-boryl substituted allylboronate reagents 2 (eq 3, Scheme 1). Specifically, Pt-catalyzed regioselective diboration of alkoxy- or amino-substituted allenes 1 occurred at the terminal olefin unit to afford allylboronates 2 with excellent Z-selectivity. Subsequent addition of allylboron reagents 2 to aldehydes produced 1,2-syn-diols and amino alcohols that contain a vinyl Bpin group in good yields with high diastereoselectivities. We began our studies by identifying a suitable approach for stereoselective syntheses of reagents 2. It is well-known that Ptcatalyzed diboration of monoalkyl-substituted allenes typically occurs at the more substituted alkene unit to give β-boryl substituted allylic boronates.11 However, different regioselectivity was observed when a heteroatom, for instance O or S, is directly connected to allenes. Pt-catalyzed diboration of these allenes occurs at the terminal alkene unit to provide Zallylboronates with moderate to high selectivity. Inspired by these early studies, we envisioned that (Z)-γ-alkoxy- or (Z)-γ-

1,2-Syn-3-ene-diols and amino alcohols are important structural motifs in numerous biologically active natural products and pharmaceutical agents.1,2 The addition of (Z)-γ-alkoxy- or (Z)γ-amino-allylic organometallics to carbonyl compounds is one classic approach to synthesize these molecules.3 Over the past three decades, many allylation reagents, allylboron reagents in particular, have been developed to access these chemical entities.4−6 On the other hand, addition of a β-boryl substituted (Z)-allylation reagent (e.g., 2 in Scheme 1) to aldehydes will Scheme 1. Approaches to syn-β-Alkoxy- or syn-β-Amino-γboryl Substituted Homoallylic Alcohols

produce 1,2-syn-diols or amino alcohols, and more importantly, the olefin unit in homoallylic alcohol products contains a Bpin group that can be used as a handle for a variety of subsequent transformations. However, methods that allow for stereoselective preparation of such reagents are underdeveloped.7 Trost and co-workers showed that (Z)-γ-amino-β-boryl substituted allylboronate B can be prepared with high Zselectivity through Ru-catalyzed olefin transposition from vinyl © 2019 American Chemical Society

Received: May 1, 2019 Published: June 12, 2019 4638

DOI: 10.1021/acs.orglett.9b01535 Org. Lett. 2019, 21, 4638−4641

Letter

Organic Letters

yield after in situ protection of the resulting secondary hydroxyl group. Scheme 4 summarizes the scope of aldehyde that

amino-β-boryl substituted allylboronates 2 should be available in one step via Pt-catalyzed regioselective diboration of readily available alkoxy- or aminoallenes 1. The initial experiments on diboration of methoxyallene 1a12 were conducted under the conditions developed by the Miyaura group.11a In the presence of 5 mol % Pt(PPh3)4, diboration of allene 1a at 70 °C in toluene produced a 3:1 inseparable Z/E mixture of allylboronates 2a and 3a in 55% combined yield, with 2a as the major product. Diboration of 1a with the combination of 5 mol % Pt(dba)3 and 5 mol % PCy3 as the catalyst system is much more selective. Allylboronate 2a was obtained in 80% yield with exclusive Zselectivity (Scheme 2). Product from diboration at methoxysubstituted olefin unit was not observed in both reactions.

Scheme 4. Scope of Aldehyde for Reactions with (Z)-γAlkoxy-β-boryl Substituted Allylboronates 2a,b,c

Scheme 2. Synthesis of Allylboronate 2a

The conditions were applied to diboration of several alkoxyor amino-allenes. As shown in Scheme 3, the reaction with Scheme 3. Pt-Catalyzed Regio- and Stereoselective Diboration of Alkoxyallenes and Aminoallenesa,b,c

a Allene 1 (0.12 mmol, 1.2 equiv), Pt(dba)3 (5 mol %), PCy3 (5 mol %), B2pin2 (0.1 mmol, 1 equiv), toluene (0.5 mL), 70 °C. bZ/Eselectivities were determined by 1H NMR analysis of the crude reaction product. cYields of isolated products are listed. dAllene 1 (0.12 mmol, 1.2 equiv), Pd(dba)2 (5 mol %), B2pin2 (0.1 mmol, 1 equiv), I2 (5 mol %), toluene (0.5 mL), 80 °C.

a

Reaction conditions: allylboronate 2 (0.12 mmol, 1.2 equiv), aldehyde (0.1 mmol, 1.0 equiv), toluene (0.2 mL), 70 °C, then TESCl (0.2 mmol, 2 equiv), imidazole (0.2 mmol, 2 equiv), rt. bYields of isolated products are listed. cReaction was conducted with 0.2 mmol of aldehyde and 0.1 mmol of allylboronate 2a. dReactions were conducted at 80 °C.

benzyloxy-substituted allene13 gave allylboronate 2b in 83% yield. Diboration of aminoallenes 1d−f16−18 occurred smoothly to give (Z)-γ-amino-allylboronates 2d−f in 84−86% yields with excellent regio- and Z-selectivities. In 1 mmol scale reactions, allylboronates 2b and 2d were obtained in 83−84% yields with >20:1 Z-selectivity. It is interesting to note that phenoxysubstituted allene 1c14 did not react under the standard conditions. However, by adopting the Pd-catalyzed diboration protocol developed by the Cheng group, diboration of this allene did occur to give allylboronate 2c in 87% yield.15 Reactions of aldehyde with the obtained (Z)-allylboronates 2 were examined. The rate of aldehyde allylation is slow at ambient temperature. However, the reaction of allylboronate 2a with benzaldehyde was complete within 48 h at elevated temperature (70 °C). And TES-ether 4a was isolated in 67%

participated in allylation reactions with (Z)-γ-alkoxy-β-borylsubstituted allylboronates 2a−c. In general, the reactions worked well with various aldehydes to give TES-protected homoallylic alcohols 4 in good yields with high diastereoselectivities. Reactions of benzaldehyde with allylboronates 2b−c gave syn-adducts 4b−c in 75−81% yields. The syn-relative stereochemistry of product 4b was confirmed by comparing the spectroscopic data of the product obtained from the protodeboration and TES-deprotection reaction sequence to the literature data.19 Aromatic aldehydes bearing a substituent with various electronic properties or substitution patterns reacted smoothly with allylboronate 2a to give products 4d−i in 65−88% yields with excellent diastereoselectivities. Reactions 4639

DOI: 10.1021/acs.orglett.9b01535 Org. Lett. 2019, 21, 4638−4641

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Organic Letters of α,β-unsaturated aldehydes with 2a afforded products 4j−l in 46−88% yields. Heteroaromatic aldehydes reacted with allylboronates 2a−b to provide 4m−p in 64−84% yields. Finally, reactions of aliphatic aldehydes with boronates 2a and 2c gave TES-protected syn-products 4q−r in 58−61% yields. Next we explored the scope of aldehyde that reacted with (Z)γ-amino-β-boryl-substituted allylboronates 2d−f. As summarized in Scheme 5, a variety of aldehydes, including aromatic,

The products (4 or 5) generated from the syn-alkoxy- or synamino-allylation reactions contain a vinyl-Bpin group that can undergo a variety of transformations. As shown in Scheme 7, Scheme 7. Transformation of the Reaction Product

Scheme 5. Scope of Aldehyde for Reactions with (Z)-γAmino-β-boryl Substituted Allylboronate 2a,b,c

product 4b was oxidized with NaBO3 to give methyl ketone 8 in 88% yield. The vinyl boronate unit in 4b can also be converted into a vinyl bromide group using CuBr2, and vinyl bromide 9 was obtained in 90% yield.20 The silyl ether was deprotected under the reaction conditions. Vinyl bromide 9 should be able to react with various aryl or vinyl nucleophiles in transition-metalcatalyzed cross-coupling reactions. On the other hand, the vinyl boronate unit in product 4b can be directly used in crosscoupling reactions to form a C−C bond. For example, Pdcatalyzed Suzuki coupling of 4b with iodobenzene gave 10 in 85% yield after deprotection of the TES ether with TBAF.21 Additionally, the vinyl boronate can be used for C−O bond formation. Cu(OAc)2 mediated reaction of 4b with allyl alcohol gave allyl ether 11 in 61% yield.22 In summary, we developed a regio- and stereoselective diboration approach to access (Z)-γ-alkoxy- or (Z)-γ-amino-βboryl substituted allylboronates. Subsequent allylboration of aldehydes with these allylboron reagents followed by protection of the secondary hydroxyl group gave TES-protected syn-βalkoxy- or syn-β-amino-γ-boryl-substituted homoallylic alcohols with high diastereoselectivities. Importantly, products generated from these reactions contain a vinyl boronate group that is amenable to a variety of subsequent transformations. Synthetic application of this method will be reported in due course.23

a

Reaction conditions: allylboronate 2 (0.12 mmol, 1.2 equiv), aldehyde (0.1 mmol, 1.0 equiv), toluene (0.2 mL), 60 °C, then TESCl (0.2 mmol, 2 equiv), imidazole (0.2 mmol, 2 equiv), rt. bYields of isolated products are listed. cThe reaction was conducted at 80 °C. d The reaction was conducted at 100 °C.

heteroaromatic, α,β-unsaturated, and aliphatic aldehydes, all reacted with allylboronate 2d to give TES-protected syn-βamino-homoallylic alcohols 5a−f in 62−86% yields after in situ protection. The syn-relative stereochemistry of product 5e was confirmed by X-ray crystallography. Reactions with allylboronates 2e−f were slow. However, with prolonged heating at slightly elevated temperature (80 or 100 °C) with excess benzaldehyde, products 5g−h were obtained in synthetically useful yields. Reaction of chiral aldehyde 6 with allylboronate 2a was examined. Although the reaction rate is slow, product 7 was synthesized in 81% yield with 5:1 diastereoselectivity in the presence of excess aldehyde 6 (Scheme 6).

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ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.orglett.9b01535. Experimental procedures, spectra for all new compounds (PDF)

Scheme 6. Reaction of 2a with Chiral Aldehyde 6

Accession Codes

CCDC 1904534 contains the supplementary crystallographic data for this paper. These data can be obtained free of charge via 4640

DOI: 10.1021/acs.orglett.9b01535 Org. Lett. 2019, 21, 4638−4641

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Organic Letters

8429. (d) Gao, X.; Hall, D. G. J. Am. Chem. Soc. 2005, 127, 1628. (e) Lessard, S.; Peng, F.; Hall, D. G. J. Am. Chem. Soc. 2009, 131, 9612. (f) Penner, M.; Rauniyar, V.; Kaspar, L. T.; Hall, D. G. J. Am. Chem. Soc. 2009, 131, 14216. (7) For references on studies that generate γ-silyl-substituted homoallylic alcohols, see: (a) Chang, K. J.; Rayabarapu, D. K.; Yang, F. Y.; Cheng, C. H. J. Am. Chem. Soc. 2005, 127, 126. (b) Helm, M. D.; Mayer, P.; Knochel, P. Chem. Commun. 2008, 1916. (c) Zbieg, J. R.; Moran, J.; Krische, M. J. J. Am. Chem. Soc. 2011, 133, 10582. (d) Miura, T.; Nishida, Y.; Murakami, M. J. Am. Chem. Soc. 2014, 136, 6223. (e) Rae, J.; Hu, Y. C.; Procter, D. J. Chem. - Eur. J. 2014, 20, 13143. (f) Trost, B. M.; Koester, D. C.; Sharif, E. U. Chem. - Eur. J. 2016, 22, 2634. (8) Trost, B. M.; Cregg, J. J.; Quach, N. J. Am. Chem. Soc. 2017, 139, 5133. (9) Miura, T.; Nakahashi, J.; Sasatsu, T.; Murakami, M. Angew. Chem., Int. Ed. 2019, 58, 1138. (10) (a) Wang, M.; Khan, S.; Miliordos, E.; Chen, M. Org. Lett. 2018, 20, 3810. (b) Wang, M.; Khan, S.; Miliordos, E.; Chen, M. Adv. Synth. Catal. 2018, 360, 4634. (c) Gao, S.; Wang, M.; Chen, M. Org. Lett. 2018, 20, 7921. (d) Gao, S.; Chen, J.; Chen, M. Chem. Sci. 2019, 10, 3637. (11) (a) Ishiyama, T.; Kitano, T.; Miyaura, N. Tetrahedron Lett. 1998, 39, 2357. (b) Pelz, N. F.; Woodward, A. R.; Burks, H. E.; Sieber, J. D.; Morken, J. P. J. Am. Chem. Soc. 2004, 126, 16328. (c) Woodward, A.; Burks, H. E.; Chan, L. M.; Morken, J. P. Org. Lett. 2005, 7, 5505. (d) Burks, H. E.; Liu, S.; Morken, J. P. J. Am. Chem. Soc. 2007, 129, 8766. (12) For a recent review on alkoxyallene in chemical synthesis, see: Zimmer, R.; Reissig, H.-U. Chem. Soc. Rev. 2014, 43, 2888. (13) (a) Trost, B. M.; Xie, J. J. Am. Chem. Soc. 2006, 128, 6044. (b) Lippincott, D. J.; Linstadt, R. T. H.; Maser, M. R.; Lipshutz, B. H. Angew. Chem., Int. Ed. 2017, 56, 847. (14) (a) Wang, Y.; Jiang, M.; Liu, J.-T. Adv. Synth. Catal. 2014, 356, 2907. (b) Bernar, I.; Fiser, B.; Blanco-Ania, D.; Gómez-Bengoa, E.; Rutjes, F. P. J. T. Org. Lett. 2017, 19, 4211. (15) (a) Yang, F.-Y.; Cheng, C.-H. J. Am. Chem. Soc. 2001, 123, 761. (b) Kidonakis, M.; Stratakis, M. ACS Catal. 2018, 8, 1227. (16) (a) Kimber, M. C. Org. Lett. 2010, 12, 1128. (b) Hill, A. W.; Elsegood, M. R. J.; Kimber, M. C. J. Org. Chem. 2010, 75, 5406. (c) Villar, L.; Uria, U.; Martinez, J. I.; Prieto, L.; Reyes, E.; Carrillo, L.; Vicario, J. L. Angew. Chem., Int. Ed. 2017, 56, 10535. (17) Lindsay, V. N. G.; Fiset, D.; Gritsch, P. J.; Azzi, D.; Charette, A. B. J. Am. Chem. Soc. 2013, 135, 1463. (18) (a) Suárez-Pantiga, S.; Hernández-Díaz, C.; Piedrafita, M.; Rubio, E.; González, J. M. Adv. Synth. Catal. 2012, 354, 1651. (b) Sabbatani, J.; Huang, X.; Veiros, L. F.; Maulide, N. Chem. - Eur. J. 2014, 20, 10636. (c) Zheng, W. F.; Bora, P. P.; Sun, G. J.; Kang, Q. Org. Lett. 2016, 18, 3694. (d) García, L.; Sendra, J.; Miralles, N.; Reyes, E.; Carbó, J. J.; Vicario, J. L.; Fernández, E. Chem. - Eur. J. 2018, 24, 14059. (19) Kobayashi, S.; Endo, T.; Ueno, M. Angew. Chem., Int. Ed. 2011, 50, 12262. (20) (a) Murphy, J. M.; Liao, X.; Hartwig, J. F. J. Am. Chem. Soc. 2007, 129, 15434. (b) Miura, T.; Nakahashi, J.; Zhou, W.; Shiratori, Y.; Stewart, S. G.; Murakami, M. J. Am. Chem. Soc. 2017, 139, 10903. (21) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457. (b) Wang, M.; Gao, S.; Chen, M. Org. Lett. 2019, 21, 2151. (22) (a) Shade, R. E.; Hyde, A. M.; Olsen, J.-C.; Merlic, C. A. J. Am. Chem. Soc. 2010, 132, 1202. (b) Winternheimer, D. J.; Merlic, C. A. Org. Lett. 2010, 12, 2508. (23) Preliminary studies on chiral phosphoric acid catalyzed enantioselective aldehyde allylboration with reagents 2 give products with low ee. The Murakami group also reported similar results; please see ref 9.

www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_ [email protected], or by contacting The Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax: +44 1223 336033.

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AUTHOR INFORMATION

Corresponding Author

*E-mail: [email protected]. ORCID

Shang Gao: 0000-0001-8166-5503 Ming Chen: 0000-0002-9841-8274 Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS Financial support provided by Auburn University is gratefully acknowledged. We thank AllylChem for a generous gift of B2pin2.

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REFERENCES

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DOI: 10.1021/acs.orglett.9b01535 Org. Lett. 2019, 21, 4638−4641