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. 2020 Dec 3;142(51):21254–21259. doi: 10.1021/jacs.0c09923

Organocatalytic Synthesis of α-Trifluoromethyl Allylboronic Acids by Enantioselective 1,2-Borotropic Migration

Sybrand J T Jonker †, Ramasamy Jayarajan †, Tautvydas Kireilis †, Marie Deliaval †, Lars Eriksson ‡, Kálmán J Szabó †,*
PMCID: PMC7760092  PMID: 33270462

Abstract

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Chiral α-substituted allylboronic acids were synthesized by asymmetric homologation of alkenylboronic acids using CF3/TMS-diazomethanes in the presence of BINOL catalyst and ethanol. The chiral α-substituted allylboronic acids were reacted with aldehydes or oxidized to alcohols in situ with a high degree of chirality transfer. The oxygen-sensitive allylboronic acids can be purified via their isolated diaminonaphthalene (DanH)-protected derivatives. The highly reactive purified allylboronic acids reacted in a self-catalyzed reaction at room temperature with ketones, imines, and indoles to give congested trifluoromethylated homoallylic alcohols/amines with up to three contiguous stereocenters.

Chiral allylboronic acids1 are ideal reagents for asymmetric synthesis because of their high reactivity in self-catalyzed allylboration reactions that occur with high stereochemical fidelity. However, the synthesis of chiral allylboronic acids has been an unmet challenge in organic synthesis. Our experience with Pd-catalyzed synthesis of (achiral) allylboronic acids2 (Figure 1a) and conclusions based on related mechanistic studies3 suggested that a metal-free approach would be rewarding for effective control of the stereoselectivity. We hypothesized that the synthesis of chiral allylboronic acids may be devised by using an organocatalytic homologation strategy. The first methods for asymmetric homologation of organoboron compounds were reported by the Matteson group.4,5 Aggarwal and co-workers6 applied a useful lithiation–borylation method (Figure 1b) for the synthesis of chiral allyl-Bpin species,7 including an example of an α-trifluoromethyl allylboronate derivative.8 This method is based on stoichiometric formation of chiral lithium carbenoid intermediates, and therefore, it is not suitable for the direct synthesis of allylboronic acids. The Ley9−11 and Wang12 groups (Figure 1c) reported a homologation method based on diazo carbenoid reagents. This method was suitable for the synthesis of (achiral) allylboronic acids, which were used in one-pot allylborations9,11 or converted to their Bpin derivatives.12 A similar approach was employed by Molander and co-workers (Figure 1c) for the synthesis of benzylboronic acids from trifluoromethyl diazomethane.13,14 Arnold and co-workers presented a method for the synthesis of chiral α-CF3 alkyl- and benzylboron compounds by directed evolution of enzymes.15,16 Fluorinated organoboronates are useful reagents for selective synthesis of organofluorines.13−21 The CF3 motif very often occurs22−24 in pharmaceuticals and agrochemical products (Figure 1d).25−29

Figure 1.

Figure 1

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Synthesis of organoboronates and boronic acids as well as examples of bioactive molecules with a CF3 group.

Here we present a new methodology for the synthesis of chiral α-CF3 allylboronic acids (Figure 1e). Our concept (Figure 2) is based on reacting alkenylboroxine 2, trifluoromethyl diazomethane 3, catalytic amounts of BINOL (4),30−36 and stoichiometric amounts of EtOH. Alkenylboroxine 2 readily reacts with diazo compound 3.9−11 However, this reaction results in racemic product, such as rac-1-OR. The racemic background reaction can be avoided by addition of EtOH to the reaction mixture, which forms unreactive alkylboronic esters 2-OEt, which are weaker Lewis acids37 than the corresponding boroxines 2.30,31 Because of the dynamic covalent bonding38 ability of boron, BINOL 4 undergoes transesterification with 2-OEt to form chiral alkenyl boronate A. Exchange of the alkyl group to an aromatic moiety leads to a substantial increase in the Lewis acidity of boron,37 and therefore, A and 3 form ate complex B in the stereoinduction step of the process (see Figure S3). Then the alkenyl group undergoes stereoselective 1,2-migration10,39 to afford C. Subsequently, ethanolysis of C gives product 1-OEt.

Figure 2.

Figure 2

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Concept of catalytic asymmetric homologation with 1,2-borotropic migration.

The optimal conditions for the homologation involved using 2a with an excess of 3, 20 mol % 4 and 2 equiv of EtOH (Table 1, entry 1). The oxygen-sensitive allylboronic ester 1a-OEt was protected with diaminonaphthalene (DanH)40 to give 5a with 98% ee in 69% yield. When the reaction was repeated with 10 mol % catalyst 4, the yield was substantially lowered (12%), but the enantioselectivity was practically unchanged (96% ee) (entry 2). Replacement of iodo-BINOL 4 with bromo-BINOL (entry 3) led to decreases in the yield (9%) and the enantioselectivity (88% ee). Interestingly, increasing the loading of bromo-BINOL (entry 4) to 30 mol % led to a high yield (73%) and selectivity (94% ee). When bulky γ-substituents were employed in the BINOL catalyst (entry 5), both the yield and selectivity strongly declined. Application of the parent BINOL as the catalyst gave a low yield (4%) and relatively low selectivity (72% ee). When a commercially available alkenylboronic acid was used as the substrate (entry 7), the reaction proceeded in poor yield (18%) but with excellent selectivity (97% ee). When EtOH was replaced by iPrOH (entry 8), the yield dropped (44%) but the selectivity was still high (96% ee). In the absence of EtOH (entry 9), a complex reaction mixture was obtained, from which 5a was isolated in 4% yield with 47% ee. The poor enantioselectivity can be rationalized by the racemic background reaction (2 + 3 → rac-1-OR in Figure 2). The complex reaction mixture is a consequence of the poor stability of 1 and its boroxine in the absence of EtOH. Simple aliphatic alcohols esterify the boronic acids/boroxines and thus protect them from decomposition under the reaction conditions of the borylation (Figure 1a).2,32,41 When both EtOH and the BINOL catalyst were omitted (entry 10), a complex reaction mixture was obtained again. Without molecular sieves (entry 11), the yield was poor, probably because the slow formation of chiral alkenyl-BINOL-type intermediate A (Figure 2). At room temperature, changing dichloromethane (DCM) to toluene leads to lowering the yield and a slight decrease of the ee (entries 12–13).

Table 1. Optimal Conditions for Synthesis of α-CF3 Allylboronic Acidsa.

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a

Boroxine 2a (0.033 mmol, equivalent to 0.1 mmol of the boronic acid), 3 (0.3 mmol), 4 (0.02 mmol, 20 mol %), and ethanol (0.2 mmol) were reacted in DCM (0.8 mL) for 48 h at 40 °C, and then DanH (0.15 mmol) was added.

b

Yields of 5a determined by 19F NMR spectroscopy.

c

Isolated yields.

d

A complex reaction mixture was obtained.

Under the optimal conditions, alkyl-substituted alkenylboronic acids 2a–c reacted readily to give the corresponding α-CF3 allylboronic acid esters 1(a-c)-OEt and Bdan derivatives 5a–c (Figure 3a). Aryl-substituted alkenylboronic acids (2d–g) reacted somewhat slower than the aliphatic ones. Cinnamyl derivative 5d was formed in 54% yield (93% ee) when 20 mol % catalyst was used. However, with 20 mol % catalyst, 5e formed only in 26% yield (89% ee). Therefore, the catalyst loading was increased to 30 mol % to obtain acceptable yields of 5e–g (50–70%). The absolute configuration of crystalline 5e was determined to be S by X-ray diffraction. On the basis of the structural similarities of the substrates and the reaction conditions, we assumed that the absolute configuration of the other species (5a–d, 5f, and 5g) was the same. The reactions can be easily scaled up. For example, the synthesis of 5a on 1 and 2 mmol scales occurred with 98 and 96% ee in 78 and 68% yield, respectively.

Figure 3.

Figure 3

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Synthesis and applications of chiral α-substituted allylboronic acids. a1 mmol scale. b2 mmol scale. c30 mol % 4 was used. dAt 30 °C. e6b (0.15 mmol) was used.

The transient allylboron compounds 1-OEt reacted with aldehyde 6a in situ (Figure 1b). The enantioselectivity for the formation of 7a–d varied between 90 and 98% ee. In addition, only one of the four possible diastereomers was formed in each case. We did not detect any Z isomer of 7a–e in the crude product of the reaction. Usually, α-substituted allylboron compounds with bulky protecting groups (e.g., pinacol or 9-BBN) react with poor E/Z selectivity in allylboration reactions.42,43

These selectivity issues can often be solved by application of additives, but in the presented processes, poor E/Z selectivity was avoided by the small size of the B(OEt)2 group. Notably, small molecules with alkenyl-CF3 motifs44−48 are very important drugs, such as in anticancer agents,25 pesticides,26 and herbicides27 (Figure 1d). Formation of 7e from 1f proceeded with 75% ee. The relatively low enantioselectivity is a consequence of the fact that 1f-OEt is formed with lower selectivity (86% ee, 5f) than other allylboronic acids. The yields are in the range of 41–60% based on alkenylboronic acid monomers after a two-step process. Another useful reaction is the stereoselective in situ oxidation of the chiral allylboron compounds to the corresponding α-CF3 allylic alcohols 8a–c (Figure 3c), which were obtained in 50–78% yield with 90–99% ee. The corresponding trifluoroethanol motif49,50 occurs for example in antitumor agent Z28 and the monoamine oxidase inhibitor befloxatone (Figure 1d).29

The asymmetric homologation concept can also be extended to the synthesis of chiral α-silyl allylboronic acids, such as 1h-OEt (Figure 3d). In this reaction, 3 was replaced with TMS-diazomethane. Dan protection of 1h-OEt failed, and therefore, we isolated pinane derivative 9. The homologation affording 9 proceeded with high selectivity (99:1 d.r., corresponding to 98% ee for 1h-OEt) in 51% yield. In situ allylboration of 6a gave homoallylic alcohol 10 with high selectivity.

We were able to obtain purified oxygen-sensitive allylboronic acids such as 1a and 1d by hydrolysis of the corresponding isolated Dan-protected products (5a and 5d) (Table 2). The increased reactivity of the purified products unleashed the outstanding synthetic potential of chiral allylboronic acids. As we reported previously, in the presence of molecular sieves (or other drying agents), pure allylboronic acids form very reactive allylboroxines.2,30,31,37 Purified 1a in the presence of molecular sieves reacted with 6a in just 10 min to afford 7a (Table 2, entry 1). Notably, the enantioselectivities with purified and in situ-formed 1a were identical. This was also confirmed by the reaction of cinnamyl analogue 1d with 6a (entry 2). Allylboration of 6b with in situ-generated 1a-OEt failed to give 7f (Figure 3b). However, purified 1a in the presence of molecular sieves gave 1a-boroxine (see the Supporting Information), which reacted with 6b to afford 7f (entry 3) with excellent selectivity (98% ee) in 67% yield. The purification (1a-OEt → 5a → 1a sequence) is essential to obtain 7f, as demonstrated by a control experiment (entry 4). When 2 equiv of EtOH was added to 1a prior to addition of 6b, formation of 7f was not observed. Likewise, 1a-Bpin did not react with 6b under the reaction conditions applied for 1a (entry 5). Aliphatic ketones (6c–e) also reacted smoothly with allylboronic acids. Cyclohexanones 6c and 6d gave the corresponding products 7g and 7h with 91–97% ee in 50–72% yield (entries 6 and 7). The reaction of racemic methyl cyclohexanone 6d with 1d is spectacular, as in this reaction the major enantiomer (97% ee) 7h was formed with three contiguous stereocenters in a single reaction step. Acyclic aliphatic ketone 6e reacted in high yield (72%) but with only 82% ee, affording densely functionalized tertiary homoallyl alcohol 7i. The synthetic utility of purified chiral allylboronic acids was further demonstrated by allylboration of indoles11,31,51,526f and 6g with 1d to afford 7j and 7k with high selectivities (entries 9 and 10). From skatole 6g, the E-alkenyl-CF3 product 7k with three adjacent stereocenters was formed with 89% ee. Isoquinoline derivative31,536h reacted with purified 1d to afford 7m with 93% ee in 54% yield. Allylboration of 6i(54,55) with 1a gave α-amino acid derivative 7n with 98% ee in 72% yield.

Table 2. Showcase for Application of Purified α-CF3 Allylboronic Acids in Stereoselective Synthesisa.

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a

Unless otherwise stated, 5 (0.1 mmol) was hydrolyzed with 3 N H2SO4 in DME, and then 1 was extracted with toluene under Ar.

b

Isolated yields.

c

1H NMR spectra of 1a and 1d are given in the Supporting Information.

d

Using 2 equiv of EtOH without molecular sieves.

e

1a-Bpin and 6b were stirred at 40 °C without molecular sieves.

In summary, we have presented a new methodology for the catalytic synthesis of chiral α-CF3 or α-SiMe3 allylboronic acids using stabilized diazomethane derivatives. The basic concept of stereoselective 1,2-borotropic migration can certainly be extended to nonstabilized diazoalkanes as well by solving the issues of electrophilic side reactions (e.g., protonation of the diazoalkanes) competing with the formation of the ate complex (B). The enantioenriched α-CF3 and α-SiMe3 allylboronic acids readily undergo in situ allylboration with aldehydes or can be converted to the corresponding allylic alcohols with high levels of chirality transfer. The purified chiral allylboronic acids are very reactive and highly stereoselective reagents in the allylation of aldehydes, ketones, imines, and indoles. Very promising application areas for these types of allylboronic acids are in drug design (Figure 1d) and natural product synthesis.56−60

Acknowledgments

The authors thank the Knut and Alice Wallenberg Foundation (2018.0066) and the Swedish Research Council (2017-04235) for financial support. A postdoctoral fellowship for R.J. from the Wenner-Gren Foundation (UPD2019-0149) is gratefully acknowledged. We thank Dr. D. Wang for performing some preliminary experiments.

Supporting Information Available

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/jacs.0c09923.

  • Materials and methods, characterization data, and NMR spectra (PDF)

  • Crystallographic data for 5e (CIF)

Author Contributions

§ S.J.T.J. and R.J. contributed equally.

The authors declare no competing financial interest.

Supplementary Material

ja0c09923_si_001.pdf (13.1MB, pdf)
ja0c09923_si_002.cif (2.7MB, cif)

References

  1. Diner C.; Szabó K. J. Recent Advances in the Preparation and Application of Allylboron Species in Organic Synthesis. J. Am. Chem. Soc. 2017, 139, 2–14. 10.1021/jacs.6b10017. [DOI] [PubMed] [Google Scholar]
  2. Raducan M.; Alam R.; Szabó K. J. Palladium-Catalyzed Synthesis and Isolation of Functionalized Allylboronic Acids: Selective, Direct Allylboration of Ketones. Angew. Chem., Int. Ed. 2012, 51, 13050–13053. 10.1002/anie.201207951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Larsson J. M.; Szabó K. J. Mechanistic Investigation of the Palladium-Catalyzed Synthesis of Allylic Silanes and Boronates from Allylic Alcohols. J. Am. Chem. Soc. 2013, 135, 443–455. 10.1021/ja309860h. [DOI] [PubMed] [Google Scholar]
  4. Matteson D. S.; Sadhu K. M. Boronic ester homologation with 99% chiral selectivity and its use in syntheses of the insect pheromones (3S,4S)-4-methyl-3-heptanol and exo-brevicomin. J. Am. Chem. Soc. 1983, 105, 2077–2078. 10.1021/ja00345a074. [DOI] [Google Scholar]
  5. Matteson D. S. Boronic Esters in Asymmetric Synthesis. J. Org. Chem. 2013, 78, 10009–10023. 10.1021/jo4013942. [DOI] [PubMed] [Google Scholar]
  6. Stymiest J. L.; Bagutski V.; French R. M.; Aggarwal V. K. Enantiodivergent conversion of chiral secondary alcohols into tertiary alcohols. Nature 2008, 456, 778–782. 10.1038/nature07592. [DOI] [PubMed] [Google Scholar]
  7. Hesse M.; Essafi S.; Watson C.; Harvey J.; Hirst D.; Willis C.; Aggarwal V. K. Highly Selective Allylborations of Aldehydes Using α,α-Disubstituted Allylic Pinacol Boronic Esters. Angew. Chem., Int. Ed. 2014, 53, 6145–6149. 10.1002/anie.201402995. [DOI] [PubMed] [Google Scholar]
  8. Nandakumar M.; Rubial B.; Noble A.; Myers E. L.; Aggarwal V. K. Ring-Opening Lithiation–Borylation of 2-Trifluoromethyl Oxirane: A Route to Versatile Tertiary Trifluoromethyl Boronic Esters. Angew. Chem., Int. Ed. 2020, 59, 1187–1191. 10.1002/anie.201912797. [DOI] [PubMed] [Google Scholar]
  9. Poh J.-S.; Lau S.-H.; Dykes I. G.; Tran D. N.; Battilocchio C.; Ley S. V. A multicomponent approach for the preparation of homoallylic alcohols. Chem. Sci. 2016, 7, 6803–6807. 10.1039/C6SC02581A. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Bomio C.; Kabeshov M. A.; Lit A. R.; Lau S.-H.; Ehlert J.; Battilocchio C.; Ley S. V. Unveiling the role of boroxines in metal-free carbon–carbon homologations using diazo compounds and boronic acids. Chem. Sci. 2017, 8, 6071–6075. 10.1039/C7SC02264F. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Forni J. A.; Lau S.-H.; Poh J.-S.; Battilocchio C.; Ley S. V.; Pastre J. C. Diastereoselective synthesis of functionalized indolines using in situ generated allyl boronic species. Synlett 2018, 29, 825–829. 10.1055/s-0036-1589164. [DOI] [Google Scholar]
  12. Wu C.; Bao Z.; Xu X.; Wang J. Metal-free synthesis of gem-silylboronate esters and their Pd(0)-catalyzed cross-coupling with aryliodides. Org. Biomol. Chem. 2019, 17, 5714–5724. 10.1039/C9OB01006H. [DOI] [PubMed] [Google Scholar]
  13. Argintaru O. A.; Ryu D.; Aron I.; Molander G. A. Synthesis and Applications of α-Trifluoromethylated Alkylboron Compounds. Angew. Chem., Int. Ed. 2013, 52, 13656–13660. 10.1002/anie.201308036. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Molander G. A.; Ryu D. Diastereoselective Synthesis of Vicinally Bis(trifluoromethylated) Alkylboron Compounds through Successive Insertions of 2,2,2-Trifluorodiazoethane. Angew. Chem., Int. Ed. 2014, 53, 14181–14185. 10.1002/anie.201408191. [DOI] [PubMed] [Google Scholar]
  15. Kan S. B. J.; Huang X.; Gumulya Y.; Chen K.; Arnold F. H. Genetically programmed chiral organoborane synthesis. Nature 2017, 552, 132. 10.1038/nature24996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Huang X.; Garcia-Borràs M.; Miao K.; Kan S. B. J.; Zutshi A.; Houk K. N.; Arnold F. H. A Biocatalytic Platform for Synthesis of Chiral α-Trifluoromethylated Organoborons. ACS Cent. Sci. 2019, 5, 270–276. 10.1021/acscentsci.8b00679. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Akiyama S.; Kubota K.; Mikus M. S.; Paioti P. H. S.; Romiti F.; Liu Q.; Zhou Y.; Hoveyda A. H.; Ito H. Catalytic Enantioselective Synthesis of Allylic Boronates Bearing a Trisubstituted Alkenyl Fluoride and Related Derivatives. Angew. Chem., Int. Ed. 2019, 58, 11998–12003. 10.1002/anie.201906283. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Morrison R. J.; van der Mei F. W.; Romiti F.; Hoveyda A. H. A Catalytic Approach for Enantioselective Synthesis of Homoallylic Alcohols Bearing a Z-Alkenyl Chloride or Trifluoromethyl Group. A Concise and Protecting Group-Free Synthesis of Mycothiazole. J. Am. Chem. Soc. 2020, 142, 436–447. 10.1021/jacs.9b11178. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Kojima R.; Akiyama S.; Ito H. A Copper(I)-Catalyzed Enantioselective γ-Boryl Substitution of Trifluoromethyl-Substituted Alkenes: Synthesis of Enantioenriched γ,γ-gem-Difluoroallylboronates. Angew. Chem., Int. Ed. 2018, 57, 7196–7199. 10.1002/anie.201803663. [DOI] [PubMed] [Google Scholar]
  20. Fager D. C.; Morrison R. J.; Hoveyda A. H. Regio- and Enantioselective Synthesis of Trifluoromethyl-Substituted Homoallylic α-Tertiary NH2-Amines by Reactions Facilitated by a Threonine-Based Boron-Containing Catalyst. Angew. Chem., Int. Ed. 2020, 59, 11448–11455. 10.1002/anie.202001184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Jiang Q.; Guo T.; Yu Z. Copper-Catalyzed Asymmetric Borylation: Construction of a Stereogenic Carbon Center Bearing Both CF3 and Organoboron Functional Groups. J. Org. Chem. 2017, 82, 1951–1960. 10.1021/acs.joc.6b02772. [DOI] [PubMed] [Google Scholar]
  22. Zhou Y.; Wang J.; Gu Z.; Wang S.; Zhu W.; Aceña J. L.; Soloshonok V. A.; Izawa K.; Liu H. Next Generation of Fluorine-Containing Pharmaceuticals, Compounds Currently in Phase II–III Clinical Trials of Major Pharmaceutical Companies: New Structural Trends and Therapeutic Areas. Chem. Rev. 2016, 116, 422–518. 10.1021/acs.chemrev.5b00392. [DOI] [PubMed] [Google Scholar]
  23. Preshlock S.; Tredwell M.; Gouverneur V. 18F-Labeling of Arenes and Heteroarenes for Applications in Positron Emission Tomography. Chem. Rev. 2016, 116, 719–766. 10.1021/acs.chemrev.5b00493. [DOI] [PubMed] [Google Scholar]
  24. Jeschke P. The Unique Role of Fluorine in the Design of Active Ingredients for Modern Crop Protection. ChemBioChem 2004, 5, 570–589. 10.1002/cbic.200300833. [DOI] [PubMed] [Google Scholar]
  25. Kung P. P.; Meng J. J.. 2-Amino Pyridine Compounds. WO 2008/059368 A2, 2008.
  26. Stubbs V. K.; Wilshire C.; Webber L. G. Cyhalothrin—a novel acaricidal and insecticidal synthetic pyrethroid for the control of the cattle tick (Boophilus microplus) and the buffalo fly (Haematobia irritans exigua). Aust. Vet. J. 1982, 59, 152–155. 10.1111/j.1751-0813.1982.tb02762.x. [DOI] [PubMed] [Google Scholar]
  27. Hemelaere R.; Desroches J.; Paquin J.-F. Introduction of the 4,4,4-Trifluorobut-2-ene Chain Exploiting a Regioselective Tsuji–Trost Reaction Catalyzed by Palladium Nanoparticles. Org. Lett. 2015, 17, 1770–1773. 10.1021/acs.orglett.5b00539. [DOI] [PubMed] [Google Scholar]
  28. Bernardon J. M.; Biadatti T.. Vitamin D Analogues. WO 03/050067 A2, 2003.
  29. Warot D.; Berlin I.; Patat A.; Durrieu G.; Zieleniuk I.; Puech A. J. Effects of Befloxatone, a Reversible Selective Monoamine Oxidase-A Inhibitor, on Psychomotor Function and Memory in Healthy Subjects. J. Clin. Pharmacol. 1996, 36, 942–950. 10.1002/j.1552-4604.1996.tb04762.x. [DOI] [PubMed] [Google Scholar]
  30. Alam R.; Vollgraff T.; Eriksson L.; Szabó K. J. Synthesis of Adjacent Quaternary Stereocenters by Catalytic Asymmetric Allylboration. J. Am. Chem. Soc. 2015, 137, 11262–11265. 10.1021/jacs.5b07498. [DOI] [PubMed] [Google Scholar]
  31. Alam R.; Diner C.; Jonker S.; Eriksson L.; Szabó K. J. Catalytic Asymmetric Allylboration of Indoles and Dihydroisoquinolines with Allylboronic Acids: Stereodivergent Synthesis of up to Three Contiguous Stereocenters. Angew. Chem., Int. Ed. 2016, 55, 14417–14421. 10.1002/anie.201608605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Zhao J.; Jonker S. J. T.; Meyer D. N.; Schulz G.; Tran C. D.; Eriksson L.; Szabo K. J. Copper-Catalyzed Synthesis of Allenylboronic Acids. Access to Sterically Encumbered Homopropargylic Alcohols and Amines by Propargylboration. Chem. Sci. 2018, 9, 3305–3312. 10.1039/C7SC05123A. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Wu T. R.; Shen L.; Chong J. M. Asymmetric Allylboronation of Aldehydes and Ketons Using 3,3′-Disubstitutedbinaphtol-Modified Boronates. Org. Lett. 2004, 6, 2701–2704. 10.1021/ol0490882. [DOI] [PubMed] [Google Scholar]
  34. Wu T. R.; Chong J. M. Ligand-Catalyzed Asymmetric Alkynylboration of Enones: A New Paradigm for Asymmetric Synthesis Using Organoboranes. J. Am. Chem. Soc. 2005, 127, 3244–3245. 10.1021/ja043001q. [DOI] [PubMed] [Google Scholar]
  35. Lou S.; Moquist P. N.; Schaus S. E. Asymmetric Allylboration of Acyl Imines Catalyzed by Chiral Diols. J. Am. Chem. Soc. 2007, 129, 15398–15404. 10.1021/ja075204v. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Jiang Y.; Schaus S. E. Asymmetric Petasis Borono-Mannich Allylation Reactions Catalyzed by Chiral Biphenols. Angew. Chem., Int. Ed. 2017, 56, 1544–1548. 10.1002/anie.201611332. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Huang G.; Diner C.; Szabó K. J.; Himo F. Mechanism and Stereoselectivity of the BINOL-Catalyzed Allylboration of Skatoles. Org. Lett. 2017, 19, 5904–5907. 10.1021/acs.orglett.7b02901. [DOI] [PubMed] [Google Scholar]
  38. Nishiyabu R.; Kubo Y.; James T. D.; Fossey J. S. Boronic acid building blocks: tools for self assembly. Chem. Commun. 2011, 47, 1124–1150. 10.1039/C0CC02921A. [DOI] [PubMed] [Google Scholar]
  39. Wang H.; Jing C.; Noble A.; Aggarwal V. K. Stereospecific 1,2-Migrations of Boronate Complexes Induced by Electrophiles. Angew. Chem., Int. Ed. 2020, 59, 16859–16872. 10.1002/anie.202008096. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Noguchi H.; Hojo K.; Suginome M. Boron-Masking Strategy for the Selective Synthesis of Oligoarenes via Iterative Suzuki–Miyaura Coupling. J. Am. Chem. Soc. 2007, 129, 758–759. 10.1021/ja067975p. [DOI] [PubMed] [Google Scholar]
  41. Selander N.; Kipke A.; Sebelius S.; Szabó K. J. Petasis Borono-Mannich Reaction and Allylation of Carbonyl Compounds via Transient Allyl Boronates Generated by Palladium Catalyzed Substitution of Allyl Alcohols. An Efficient One-Pot Route to Stereodefined a-Amino Acids and Homoallyl Alcohols. J. Am. Chem. Soc. 2007, 129, 13723–13731. 10.1021/ja074917a. [DOI] [PubMed] [Google Scholar]
  42. Fasano V.; McFord A. W.; Butts C. P.; Collins B. S. L.; Fey N.; Alder R. W.; Aggarwal V. K. How big is the pinacol boronic ester as a substituent?. Angew. Chem., Int. Ed. 2020, 59, 22403–22407. 10.1002/anie.202007776. [DOI] [PubMed] [Google Scholar]
  43. Althaus M.; Mahmood A.; Suárez J. R.; Thomas S. P.; Aggarwal V. K. Application of the Lithiation–Borylation Reaction to the Preparation of Enantioenriched Allylic Boron Reagents and Subsequent In Situ Conversion into 1,2,4-Trisubstituted Homoallylic Alcohols with Complete Control over All Elements of Stereochemistry. J. Am. Chem. Soc. 2010, 132, 4025–4028. 10.1021/ja910593w. [DOI] [PubMed] [Google Scholar]
  44. Koh M. J.; Nguyen T. T.; Lam J. K.; Torker S.; Hyvl J.; Schrock R. R.; Hoveyda A. H. Molybdenum chloride catalysts for Z-selective olefin metathesis reactions. Nature 2017, 542, 80–85. 10.1038/nature21043. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Straathof N. J. W.; Cramer S. E.; Hessel V.; Noël T. Practical Photocatalytic Trifluoromethylation and Hydrotrifluoromethylation of Styrenes in Batch and Flow. Angew. Chem., Int. Ed. 2016, 55, 15549–15553. 10.1002/anie.201608297. [DOI] [PubMed] [Google Scholar]
  46. Hafner A.; Bräse S. Efficient Trifluoromethylation of Activated and Non-Activated Alkenyl Halides by Using (Trifluoromethyl)trimethylsilane. Adv. Synth. Catal. 2011, 353, 3044–3048. 10.1002/adsc.201100528. [DOI] [Google Scholar]
  47. Imhof S.; Randl S.; Blechert S. Ruthenium catalysed cross metathesis with fluorinated olefins. Chem. Commun. 2001, 1692–1693. 10.1039/b105031c. [DOI] [PubMed] [Google Scholar]
  48. Hong H.; Li Y.; Chen L.; Li B.; Zhu Z.; Chen X.; Chen L.; Huang Y. Electrochemical Synthesis Strategy for Cvinyl–CF3 Compounds through Decarboxylative Trifluoromethylation. J. Org. Chem. 2019, 84, 5980–5986. 10.1021/acs.joc.9b00766. [DOI] [PubMed] [Google Scholar]
  49. Chen X.; Gong X.; Li Z.; Zhou G.; Zhu Z.; Zhang W.; Liu S.; Shen X. Direct transfer of tri- and di-fluoroethanol units enabled by radical activation of organosilicon reagents. Nat. Commun. 2020, 11, 2756. 10.1038/s41467-020-16380-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Xu Q.; Zhou H.; Geng X.; Chen P. Nonenzymatic kinetic resolution of racemic 2,2,2-trifluoro-1-aryl ethanol via enantioselective acylation. Tetrahedron 2009, 65, 2232–2238. 10.1016/j.tet.2009.01.058. [DOI] [Google Scholar]
  51. Ullrich P.; Schmauck J.; Brauns M.; Mantel M.; Breugst M.; Pietruszka J. Enantioselective Allylation of Indoles: A Surprising Diastereoselectivity. J. Org. Chem. 2020, 85, 1894–1905. 10.1021/acs.joc.9b02573. [DOI] [PubMed] [Google Scholar]
  52. Nowrouzi F.; Batey R. A. Regio- and Stereoselective Allylation and Crotylation of Indoles at C2 Through the Use of Potassium Organotrifluoroborate Salts. Angew. Chem., Int. Ed. 2013, 52, 892–895. 10.1002/anie.201207978. [DOI] [PubMed] [Google Scholar]
  53. Wu T. R.; Chong J. M. Asymmetric Allylboration of Cyclic Imines and Applications to Alkaloid Synthesis. J. Am. Chem. Soc. 2006, 128, 9646–9647. 10.1021/ja0636791. [DOI] [PubMed] [Google Scholar]
  54. Jonker S. J. T.; Diner C.; Schulz G.; Iwamoto H.; Eriksson L.; Szabó K. J. Catalytic asymmetric propargyl- and allylboration of hydrazonoesters: a metal-free approach to sterically encumbered chiral α-amino acid derivatives. Chem. Commun. 2018, 54, 12852–12855. 10.1039/C8CC07908K. [DOI] [PubMed] [Google Scholar]
  55. Fujita M.; Nagano T.; Schneider U.; Hamada T.; Ogawa C.; Kobayashi S. Zn-Catalyzed Asymmetric Allylation for the Synthesis of Optically Active Allylglycine Derivatives. Regio- and Stereoselective Formal a-Addition of Allylboronates to Hydrazono Esters. J. Am. Chem. Soc. 2008, 130, 2914. 10.1021/ja710627x. [DOI] [PubMed] [Google Scholar]
  56. Touré B. B.; Hall D. G. Natural Product Synthesis Using Multicomponent Reaction Strategies. Chem. Rev. 2009, 109, 4439–4486. 10.1021/cr800296p. [DOI] [PubMed] [Google Scholar]
  57. Daniels B. E.; Ni J.; Reisman S. E. Synthesis of Enantioenriched Indolines by a Conjugate Addition/Asymmetric Protonation/Aza-Prins Cascade Reaction. Angew. Chem., Int. Ed. 2016, 55, 3398–3402. 10.1002/anie.201510972. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Lu Z.; Yang M.; Chen P.; Xiong X.; Li A. Total Synthesis of Hapalindole-Type Natural Products. Angew. Chem., Int. Ed. 2014, 53, 13840–13844. 10.1002/anie.201406626. [DOI] [PubMed] [Google Scholar]
  59. Tang Q.; Fu K.; Ruan P.; Dong S.; Su Z.; Liu X.; Feng X. Asymmetric Catalytic Formal 1,4-Allylation of β,γ-Unsaturated α-Ketoesters: Allylboration/Oxy-Cope Rearrangement. Angew. Chem., Int. Ed. 2019, 58, 11846–11851. 10.1002/anie.201905533. [DOI] [PubMed] [Google Scholar]
  60. Trost B. M.; Cregg J. J.; Hohn C.; Bai W.-J.; Zhang G.; Tracy J. S. Ruthenium-catalysed multicomponent synthesis of the 1,3-dienyl-6-oxy polyketide motif. Nat. Chem. 2020, 12, 629–637. 10.1038/s41557-020-0464-x. [DOI] [PubMed] [Google Scholar]

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