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Synthesis of Enantioenriched Allylic Silanes via Nickel-Catalyzed Reductive Cross-Coupling Julie L Hofstra, Alan H Cherney, Ciara M. Ordner, and Sarah E. Reisman J. Am. Chem. Soc., Just Accepted Manuscript • Publication Date (Web): 04 Dec 2017 Downloaded from http://pubs.acs.org on December 4, 2017
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Synthesis of Enantioenriched Allylic Silanes via Nickel-Catalyzed Reductive Cross-Coupling Julie L. Hofstra, Alan H. Cherney, Ciara M. Ordner, and Sarah E. Reisman* The Warren and Katharine Schlinger Laboratory for Chemistry and Chemical Engineering, Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, United States
Supporting Information Placeholder ABSTRACT: An asymmetric Ni-catalyzed reductive cross-
coupling has been developed to prepare enantioenriched allylic silanes. This enantioselective reductive alkenylation proceeds under mild conditions and exhibits good functional group tolerance. The chiral allylic silanes prepared here undergo a variety of stereospecific transformations, including intramolecular Hosomi-Sakurai reactions, to set vicinal stereogenic centers with excellent transfer of chirality.
O
O N
SiR3 R
Br
+ Ar
Cl
(±)
Cl
N Ni Cl
SiR3
(10 mol %) CoPc (5 mol %) Mn0 (3.0 equiv) NMP, 5 °C
R
Ar
>30 examples >90% ee
Figure 1. Synthesis of Chiral Allylic Silanes by Enantioselective Ni-Catalyzed Reductive Cross-Coupling
Organosilanes are valuable organic materials with applications in medicinal chemistry,1 materials science,2 and as reagents for organic synthesis.3 In particular, chiral allylic silanes are versatile synthetic reagents that engage in a variety of highly stereoselective reactions. For example, the HosomiSakurai reaction4 is a powerful method for C–C bond formation that provides homoallylic alcohols with excellent transfer of chirality when enantioenriched allylic silanes are used.5,6 Despite the utility of this and related transformations, the enantioselective preparation of chiral allylic silanes often requires multistep sequences, or the incorporation of specific functional groups to direct the formation of the C(sp3)-Si bond. Here we describe a Ni-catalyzed asymmetric reductive cross-coupling to directly prepare enantioenriched allylic silanes from simple, readily available building blocks (Figure 1). The resulting chiral allylic silanes undergo a variety of post-coupling transformations with high levels of chirality transfer.
allylic substitution16 reactions. Asymmetric transition metalcatalyzed cross-coupling, in which the critical silicon-bearing C(sp3) stereogenic center is established in the C–C bond forming step, represents an alternative and highly modular approach to chiral allylic silanes. Indeed, the first synthesis of an enantioenriched chiral allylic silane was the Pd-catalyzed asymmetric cross-coupling between a(trimethylsilyl)benzylmagnesium bromide and 1-bromo-1propene reported by Kumada and coworkers in 1982.5a However, this method employs Grignard reagents as coupling partners, which are not stable to long-term storage and decreases the functional group compatibility of the reaction. We envisioned that a Ni-catalyzed asymmetric reductive alkenylation would address this limitation,17 in that the required (chlorobenzyl)silanes are bench stable compounds and these reactions typically exhibit good functional group tolerance. Thus, a Ni-catalyzed reductive alkenylation could provide chiral allylic silanes that were not readily accessible by other methods.
Chiral allylic silanes are most commonly prepared through diastereoselective or stereospecific transformations,7 which include the Claisen rearrangement of vinyl silanes,8 bis-silylation of allylic alcohols,9 silylene insertion of allylic ethers,10 and the alkenylation of 1,1-silaboronates.11 In addition, several enantioselective transition metal-catalyzed reactions have been developed, including the hydrosilylation of dienes,12 the silylboration of allenes13, the insertion of metal carbenoids into Si-H bonds,14 and conjugate addition15 and
Our investigations began with the coupling between (E)-1-(2-bromovinyl)-4-methoxybenzene (1) and (chloro(phenyl)methyl)trimethylsilane (2a) using chiral bis(oxazoline) ligand L1, which was optimal in our previously developed enantioselective reductive alkenylation reaction (Table 1).14 A screen of reaction parameters revealed that when the reaction is conducted at 5 °C with with N-methyl2-pyrrolidone (NMP) as the solvent,18 allylic silane 3a was formed in low yield, but with high enantioselectivity (entry
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Journal of the American Chemical Society Table 1. Optimization of Allylic Silanes
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60
SiMe3 Br
Ar
+
Ph
Cl
1
2a
NiCl2(dme) (10 mol %) ligand (11 mol %) Mn0 (3.0 equiv) additive, NMP, 5 °C Ar = 4-MeOPh
SiMe3 Ar
Ph
3a
entrya
ligand
equiv 1
additiveb
yield 4 (%)c
yield 3a (%)c
ee 3a (%)d
1
L1
1.0
none
26
20
96
2
L1
1.0
NaI
22
26
97
3
L1
1.0
CoPc
13
51
96
4
L1
1.5
CoPc
9
64
97
5
L1
2.0
CoPc
8
69
97
6
L2
2.0
CoPc
22
14
41
7
L3
2.0
CoPc
9
49
–90
8e
L1
2.0
CoPc
9
70
97
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tron-donating groups on the arene cross-coupled with universally high ee; however, in some cases the yield was diminished due to instability of the products (3e, 3g). The presence of an ortho substituent on the arene also decreased the yield of the cross-coupling product (3j). Table 2. Chlorobenzyl Silane Scopea
Ar
+ Cl
1
2a-j (1 equiv)
Reactions conducted under N2 on 0.1 mmol scale for 48 h. bNaI = 0.5 equiv; CoPc = 5 mol %. cDetermined by 1H NMR versus an internal standard. dDetermined by SFC using a chiral stationary phase. e10 mol % preformed (3R,8S)-L1·NiCl2 complex used.
Si
Ar
Mn0 (3.0 equiv) NMP, 5 °C, 2 d
SiR3
(2 equiv)
SiMe3
SiR3
L1·NiCl2 (10 mol %) CoPc (5 mol %)
R1 Br
3a-j
Ar = 4-MeOPh
SiMe2Ph
Me
SiEt3
3a
3b
3c
3d
71% yield 95% ee
61% yield 98% ee
43% yield 97% ee
15% yield 93% ee
a
SiMe3
O
O N
R
S
O
O N
N
X
3f, X=Cl: 69% yield, 96% ee 3g, X=Br: 44% yield, 97% ee (52% yield)b
homodimer: Ph
N
Bn
L3
CF3
3e
31% yield 96% ee (67% yield)b SiMe3 OMe
3h
3i
81% yield 97% ee
44% yield 96% ee
OMe
3j 21% yield 95% ee
SiMe3
a
R
L1: R = -CH2CH2L2: R = Me
SiMe3
SiMe3
OMe
R R S
SiMe3
R1
Bn
Me 3Si
4
Ph
1). We hypothesized that the presence of the bulky silyl group impeded the oxidative addition of 2a to the Ni catalyst. The addition of cobalt(II) phthalocyanine (CoPc), a cocatalyst that enables the Ni-catalyzed cross-coupling of benzyl mesylates by facilitating alkyl radical generation,19 doubled the yield of 3a (entry 3). The yield of 3a increased when excess vinyl bromide was used (entries 3−5); since the use of 2.0 equiv 1 proved most generally robust across a range of substrates, these conditions were used to evaluate the scope of the reaction (see Tables 2 and 3). A screen of other bis(oxazoline) ligands, e.g. L2 and L3, determined that L1 provided the highest enantioselectivity (entries 6−7). The use of isolated complex L1·NiCl2 gave 3a in comparable yield to the in situ generated catalyst (entry 8). Control experiments confirmed that NiCl2(dme), ligand, and Mn0 are required to form 3a.15 To demonstrate scalability, the crosscoupling was conducted on a 6.0 mmol scale, delivering 1.3 g of 3a in 74% yield and 97% ee. With the optimized conditions in hand, the scope of the silane was investigated (Table 2). Whereas strained silacyclobutane20 3b was prepared in good yield and excellent ee, the corresponding triethylsilane 3d was formed in poor yield, presumably due to the increased steric encumbrance at silicon. Substrates bearing either electron-withdrawing or elec-
Reactions conducted on 0.2 mmol scale under N2. Isolated yields; ee is determined by SFC using a chiral stationary phase. b Yield determined by 1NMR versus an internal standard.
The reaction tolerates a diverse array of functional groups on the alkenyl bromide partner (Table 3),21 including aryl boronates (6c), esters (6b, 6h), imides (6m), amides (6n), alkenyl silanes (6o), and alkyl halides (6f). For greasy substrates, m-methoxy silane 2h was used as the coupling partner to facilitate product purification (6o–6u). Alkylsubstituted alkenyl bromides performed comparably to styrenyl bromides; however, a limitation of the reaction is that Z-alkenes and tri- and tetra-substituted alkenyl bromides failed to react. By changing which enantiomer of L1 is employed, diastereomeric polyenes 6t and 6u were prepared, although the yield is decreased with the mismatched (3S,8R)-L1 catalyst. Finally, alkenyl bromides bearing furan (6q), thiophene (6r), pyridine (6k), pyrimidine (6l), and indole (6e) heterocycles could be cross-coupled, giving the corresponding allylic silanes in high ee. Functional groups that were not well tolerated include aldehydes and nitriles.22 Although halide electrophiles were the primary focus of this study, oxygen-based electrophiles were also evaluated. We were pleased to find that mesylate 7 provided 3a in 45% yield and 92% ee; the lower yield was due to incomplete conversion of the starting material (Scheme 1a). Enol triflate 8 underwent cross-coupling to afford 6a in 57% yield, again with excellent enantioselectivity (Scheme 1b). Although the
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yields were modest, we note that these reactions were conducted under the conditions developed for the organic halides with minimal re-optimization. Table 3. Vinyl Bromide Scopea SiMe3 Br
R
+
Cl
5a–u
2a or 2h
(2 equiv)
(1 equiv)
SiMe3
L1·NiCl2 (10 mol %) CoPc (5 mol %)
R
Mn0 (3.0 equiv) NMP, 5 °C, 2 d
6a–u
R1
R1
(Scheme 2c).29 Sodium borohydride reduction of imide 6m provided aminal 13, which upon exposure to formic acidcyclized to form bicycle 14 in 93% yield as a 3.8:1 mixture of diastereomers.30 The major diastereomer was isolated in 57% yield and 97% ee. Ozonolysis and reduction of the amide provided (+)-tashiromine. Scheme 1. Reactions of Oxygen-Based Electrophiles a) Mesylate Electrophile
R1 = H
SiMe3 Ar
N 3
6d
R
6a, R=Me: 72% yield, 93% ee 6b, R=OAc: 62% yield, 93% ee 6c, R=Bpin: 51% yield, 91% ee OMe MeO
6e
58% yield 94% ee
59% yield 92% ee
HO
Cl
Br
BzO
2
2
2
6f
6g
6h
42% yield 95% ee (67% yield)b
39% yield 97% ee
64% yield 96% ee
+
Ph
7
(2 equiv)
(1 equiv)
Ar
Mn 0 (3.0 equiv) NMP, 10 °C, 2 d
Ph
3a 40% yield 92% ee
Ar = 4-MeOPh
b) Enol Triflate Electrophile L1·NiCl 2 (10 mol %) CoPc (5 mol %)
SiMe3
+
OTf
Ar
Cl
Ph
8
2a
(2 equiv)
(1 equiv)
SiMe3 Ar
Mn 0
(3.0 equiv) NMP, 5 °C, 2 d Ar = 4-MePh
Ph
6a 57% yield 97% ee
n
6i, n=3: 53% yield, 97% ee 6j, n=4: 57% yield, 95% ee
N N
MeO
O
6k
MeO
68% yield 94% ee
Scheme 2. Stereospecific Reactions of Chiral Allylic Silanes 6l
N
44% yield 94% ee
a) Intramolecular Hosomi-Sakurai Me
O
TiCl4
6i N
97% ee
N
Me
Me3Si
3
3
6m
6n
6o
6p
64% yield 97% ee
48% yield 96% ee
72% yield 93% ee
47% yield 96% ee
O
R1
MsO
1
SiMe3
L1·NiCl 2 (10 mol %) CoPc (5 mol %)
SiMe3
= OMe
X
6q, X=O: 61% yield, 95% ee 6r, X=S: 57% yield, 95% ee
Me TBSO
* Ar Me
6s 62% yield 97% ee
Reactions conducted on 0.2 mmol scale under N2. Isolated yields are provided; ee is determined by SFC or HPLC using a chiral stationary phase. bYield determined by 1NMR versus an internal standard.
This reductive cross-coupling provides rapid access to functionalized chiral allylic silanes that are useful in a variety of synthetic transformations.23,24 For example, allylic silanes 6i and 6j, which contain pendant acetals, undergo stereospecific TiCl4-mediated intramolecular cyclization to form the 5- and 6-membered rings 9 and 10, respectively (Scheme 2a). The observed absolute and relative stereochemistry is consistent with an anti-SE’ mode of addition, which gives rise to the trans-substituted 5-membered ring and the cissubstituted 6-membered ring.25,26,27 Either the 2,3-cis or 2,3trans tetrahydrofurans can be prepared by Lewis-acid mediated cyclizations of alcohol 6g or chloride 6f, respectively; both proceed with excellent transfer of chirality (Scheme 2b).5b,28 The utility of the method was further demonstrated in a concise enantioselective synthesis of (+)-tashiromine
SiMe3 Ph
CH2Cl2, –78 °C
6j
TiCl4
95% ee
CH2Cl2, –78 °C
Ph
H
9 97% ee
H
H
OMe SiMe3
Ph
Ph
75% combined yield 6.0:1 dr (65% isolated yield of 10)
O
10
Me
96% ee
b) Heterocycle Synthesis
6g 97% ee
a
H
71% combined yield 6.3:1 dr (51% isolated yield of 9)
Me
with (3R,8S)-L1: (S,S)-6t, 69% yield, 40:1 dr with (±)-L1: 58% yield, 2:1 dr with (3S,8R)-L1: (R,S)-6u, 43% yield, 1:19 dr
MeO
H
O
6f 95% ee
H
EtC(OEt) 2 TMSOTf CH2Cl2, rt 99% yield 18:1 dr EtCHO TiCl4 CH2Cl2 –78 °C
91% yield >20:1 dr
SiMe3
Et
O
Ph
O
Et
Ph
11 94% ee
H [Ti]
H
O
Et H
H
then SiMe3 KOtBu Ph rt
Et
O
Ph
Cl
12 91% ee
c) Natural Product Synthesis OH
6m
NaBH 4
97% ee
EtOH, 0 °C 99% yield
SiMe3 N O
HCO 2H, 23 °C 93% yield 3.8:1 dr (57% isolated yield 14)
Ph
13 Ph
HO H N
15 (+)-tashiromine
1. O 3 /O2, CH2Cl2, MeOH, –78 °C; then NaBH 4, 0 °C 2. LiAlH 4, THF reflux 68% yield 2 steps
H N
14
O
97% ee
In summary, a highly enantioselective cross-coupling reaction has been developed for the preparation of chiral allylic silanes. The reactions proceed under mild conditions
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and tolerate a variety of functional groups. The enantioenriched allylic silanes undergo several stereospecific transformations with high transfer of chirality, which we anticipate will prove useful in an array of synthetic contexts. ASSOCIATED CONTENT
Experimental procedures, characterization and spectral data for all compounds, and crystallographic data (CIF). This material is available free of charge via the Internet at http://pubs.acs.org. AUTHOR INFORMATION Corresponding Author
*
[email protected] ACKNOWLEDGMENT
We thank Dr. Scott Virgil and the Caltech Center for Catalysis and Chemical Synthesis for access to analytical equipment. We also thank Dr. Michael K. Takase and Mr. Lawrence M. Henling for assistance with X-ray crystallography, as well as Dr. Mona Shahgholi and Naseem Torian for assistance with mass spectrometry measurements. Fellowship support was provided by the National Science Foundation (Graduate Research Fellowship, J. L. H., A. H. C., Grant No. DGE-1144469) and Caltech SURF program (Richard H. Cox and John Stauffer Fellowships, C. M. O.). S. E. R. is an American Cancer Society Research Scholar and Heritage Medical Research Institute Investigator. Financial support from the NIH (R35GM118191-01; GM111805-01) is gratefully acknowledged. REFERENCES
1
(a) Showell, G. A.; Mills, J. S. Drug. Discov. Today 2003, 8, 551.(b) Min, G. K.; Hernandez, D.; Skrydstrup, T. Acc. Chem. Res. 2013, 46, 457. (c) Franz, A. K.; Wilson, S. O. J. Med. Chem. 2013, 56, 388. 2 Organosilicon Chemistry V: From Molecules to Materials; Auner, N., Weis, J., Eds.; Wiley-VCH: Weinheim, Germany, 2004. 3 Reviews: (a) Chan, T. H.; Wang, D. Chem. Rev. 1992, 92, 995. (b) Masse, C. E.; Panek, J. S. Chem. Rev. 1995, 95, 1293. (c) Fleming, I.; Barbero, A.; Walter, D. Chem. Rev. 1997, 97, 2063. (d) Chabaud, L.; James, P.; Landais, Y. Eur. J. Org. Chem. 2004, 15, 3173. 4 (a) Hosomi, A.; Sakurai, H. Tetrahedron Lett. 1976, 17, 1295. (b) Hosomi, A.; Endo, M.; Sakurai, H. Chem. Lett. 1976, 5, 941. (c) Kira, M.; Kobayashi, M.; Sakurai, H. Tetrahedron Lett. 1987, 28,4081. (d) Kira, M.; Sato, K.; Sakaurai, H. J. Am. Chem. Soc. 1990, 112, 257. (d) Chemler, S. R.; Roush, W. R. J. Org. Chem. 1998, 63, 3800. 5 Seminal reports: (a) Hayashi, T.; Konishi, M.; Ito, H.; Kumada, M. J. Am. Chem. Soc. 1982, 104, 4962. (b) Hayashi, T.; Konishi, M.; Kumada, M. J. Am. Chem. Soc. 1982, 104, 4963. (c) Hayashi, T.; Konishi, M.; Okamoto, Y.; Kabeta, K.; Kumada, M. J. Org. Chem. 1986, 51, 3772. 6 (a) Jain, N. F.; Takenaka, N.; Panek, J. S. J. Am. Chem. Soc. 1996, 118, 12475. (b) Hu, T.; Takenaka, N.; Panek, J. S. J. Am. Chem. Soc. 1999, 121, 9229. (c) Berger, R.; Duff, K.; Leighton, J. L. J. Am. Chem. Soc. 2004, 126, 5686. (d) Park, P. K.; O’Malley, S. J.; Schmidt, D. R.; Leighton, J. L. J. Am. Chem. Soc. 2006, 128, 2796. (e) Kim, H.; Ho, S.; Leighton, J. L. J. Am. Chem. Soc. 2011, 133, 6517.
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Recent catalytic asymmetric methods to prepare chiral, non-allylic silanes: (a) Chen, D.; Zhu, D.-X.; Xu, M.-H. J. Am. Chem. Soc. 2016, 138, 1498. (b) Kan, S. B. J.; Lewis, R. D.; Chen, K.; Arnold, F. H. Science 2016, 354, 1048. (c) Gribble, Jr., M. W.; Pirnot, M. T.; Bandar, J. S.; Liu, R. Y.; Buchwald, S. L. J. Am. Chem. Soc. 2017, 139, 2192. 8 (a) Sparks, M. A.; Panek, J. S. J. Org. Chem. 1991, 56, 3431. (b) Panek, J. S.; Clark, T. D. J. Org. Chem. 1992, 57, 4323. 9 Suginome, M.; Matsumoto, A.; Ito, Y. J. Am. Chem. Soc. 1996, 118, 3061. 10 Bourque, L. E.; Cleary, P. A.; Woerpel, K. A. J. Am. Chem. Soc. 2007, 129, 12602. 11 (a) Binanzer, M.; Fang, G. Y.; Aggarwal, V. K. Angew. Chem. Int. Ed. 2010, 49, 4264. (b) Aggarwal, V. K.; Binanzer, M.; Carolina de Ceglie, M.; Gallanti, M.; Glasspoole, B. W.; Kendrick, S. J. F.; Sonawane, R. P.; Vazquez-Romero, A.; Webster, M. P. Org. Lett. 2011, 13, 1490. 12 Hayashi, T.; Han, J. W.; Takeda, A.; Tang, J.; Nohmi, K.; Mukaide, K.; Tsuji, H.; Uozumi, Y. Adv. Synth. Catal. 2001, 343, 279. 13 Ohmura, T.; Taniguchi, H.; Suginome, M. J. Am. Chem. Soc. 2006, 128, 13682. 14 (a) Davies, H. M. L.; Hansen, T.; Rutberg, J.; Bruzinski, P. R. Tett. Lett. 1997, 38, 1741. (b) Wu, J.; Chen, Y.; Panek, J. S. Org. Lett. 2010, 12, 2112. 15 (a) Shintani, R.; Ichikawa, Y.; Hayashi, T.; Chen, J.; Nakao, Y.; Hiyama, T. Org. Lett. 2007, 9, 4643. (b) Lee, K.-S.; Wu, H.; Haeffner, F.; Hoveyda, A. H.; Organomet. 2012, 31, 7823. 16 Kacprzynski, M. A.; May, T. L.; Kazane, S. A.; Hoveyda, A. H. Angew. Chem. Int. Ed. 2007, 46, 4554. 17 (a) Cherney, A. H.; Reisman, S. E. J. Am. Chem. Soc. 2014, 136, 14365. (b) Suzuki, N.; Hofstra, J. L.; Poremba, K. E.; Reisman, S. E. Org. Lett. 2017, 19, 2150. 18 See Supporting Information for additional reaction optimization data. 19 Ackerman, L. K. G.; Anka-Lufford, L. L.; Naodovic, M.; Weix, D. J. Chem. Sci. 2015, 6, 1115. 20 Matsumoto, K.; Oshima, K.; Utimoto, K. J. Org. Chem. 1994, 59, 7152. 21 The absolute stereochemistry of 6c was determined by single crystal X-ray diffraction. The stereochemical assignment of all other products were made by analogy. 22 Use of (E)-4-(2-bromovinyl)benzaldehyde or (E)-4-(2bromovinyl)benzonitrile provide the cross-coupled product in 0% and 34% yield, respectively. 23 The allylic silanes can also be employed in standard Hosomi-Sakurai crotylation reactions with excellent transfer of chirality. See Supporting Information for details. 24 The photoredox-catalyzed trifluoromethylation of chiral allylic silanes has also been reported: Mizuta, S.; Engle, K. M.; Verhoog, S.; Galicia-López, O.; O’Buill, M.; Médebielle, M.; Wheelhouse, K.; Rassias, G.; Thompson, A. L.; Gouverneur, V. Org. Lett. 2013, 15, 1250. 25 An SN2-type mechanism is also consistent with the stereochemical outcome. Denmark, S. E.; Willson, T. M. J. Am. Chem. Soc. 1989, 111, 3475. 26 Diastereomers were assigned by comparison to synthetic standards. See Supporting Information. 27 Wu, J.; Pu, Y.; Panek, J. S. J. Am. Chem. Soc. 2012, 134, 18440. 28 Suginome, M.; Iwanami, T.; Ito, Y. J. Org. Chem. 1998, 63, 6096. 29 (a) McElhinney, A. D.; Marsden, S. P. Synlett 2005, 16, 2528. (b) Park, Y.; Schindler, C. S.; Jacobsen, E. N. J. Am. Chem. Soc. 2016, 138, 14848.
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(a) Hiemstra, H.; Sno, M. H. A. M.; Vijn, R. J.; Speckamp, W. N. J. Org. Chem. 1985, 50, 4014. (b) Hubert, J. C.; Wijnberg, J. B. P. A.; Speckamp, W. N. Tetrahedron 1975, 31, 1437. TOC graphic: O
O N
N Ni
SiR3 R
Br
+ Cl
Ar
(±)
Cl
Cl
SiR3
(10 mol %) CoPc (5 mol %) Mn 0 (3.0 equiv) NMP, 5 °C
R
Ar
>25 examples >90% ee
stereoconvergent reductive alkenylation
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