CC BY-ND-NC 4.0 · Synthesis 2019; 51(01): 233-239
DOI: 10.1055/s-0037-1610309
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Silicon Grignard Reagents as Nucleophiles in Transition-Metal-Catalyzed Allylic Substitution

Weichao Xue
,
Martin Oestreich*
Institut für Chemie, Technische Universität Berlin, Strasse des 17. Juni 115, 10623 Berlin, Germany   Email: martin.oestreich@tu-berlin.de
› Author Affiliations
This research was supported by the China Scholarship Council (predoctoral fellowship to W.X., 2015–2019) and the Deutsche Forschungsgemeinschaft (Oe 249/15-1). M.O. is indebted to the Einstein Foundation Berlin for an endowed professorship.
Further Information

Publication History

Received: 24 September 2018

Accepted: 28 September 2018

Publication Date:
22 October 2018 (eFirst)

 

Published as part of the 50 Years SYNTHESIS – Golden Anniversary Issue

Abstract

A broad range of transition-metal catalysts is shown to promote allylic substitution reactions of allylic electrophiles with silicon Grignard reagents. The procedure was further elaborated for CuI as catalyst. The regioselectively is independent of the leaving group for primary allylic precursors, favoring α over γ. The stereochemical course of this allylic transposition was probed with a cyclic system, and anti-dia­stereoselectivity was obtained.


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Biographical Sketches

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Weichao Xue (born in 1989 in Pingdingshan/China) studied Chemistry at Henan University (2008–2012) and Shanghai University (2012–2015). He obtained his bachelor’s degree with Feng Shi (Kaifeng, 2012) and master’s degree with Hegui Gong (Shanghai, 2015). He then moved to Berlin to pursue doctoral research funded by the China Scholarship Council (2015–2019). Currently, he is a Ph.D. candidate in the group of Martin Oestreich at the Technische Universität Berlin. He is also a member of the Berlin Graduate School of Natural Sciences­ and Engineering (BIG-NSE­) of the Cluster of Excellence Unifying Concepts in Catalysis of the Deutsche Forschungsgemeinschaft.

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Martin Oestreich (born in 1971 in Pforzheim/Germany) is Professor of Organic Chemistry at the Technische Universität Berlin. He received his diploma degree with Paul Knochel (Marburg, 1996) and his doctoral degree with Dieter Hoppe (Münster, 1999). After a two-year postdoctoral stint with Larry E. Overman (Irvine, 1999–2001), he completed his habilitation with Reinhard Brückner (Freiburg, 2001–2005) and was appointed as Professor of Organic Chemistry at the Westfälische Wilhelms-Universität Münster (2006–2011). He also held visiting positions at Cardiff University in Wales (2005), The Australian National University in Canberra (2010), and Kyoto University (2018).

Allylic silanes are an often-used class of silicon reagents and continue to be widely applied in synthesis.[1] Several methods are available that provide reliable access to these compounds.[2] [3] [4] [5] [6] One established methodology is by transition-metal-catalyzed allylic substitution of allylic precursors with silicon (pro)nucleophiles such as Si–Si[2] and Si–B[3] compounds as well as zinc[4] reagents. Examples with copper complexes as catalysts pertinent to the present study are summarized in Scheme [1] (top). The reverse approach, that is, the nucleophilic displacement at silicon electrophiles with carbon nucleophilic, is far less general.[5]

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Scheme 1 Copper-catalyzed allylic substitution with silicon (pro)nucleophiles (top; LG: leaving group) and preparation of silicon Grignard reagents (bottom)

We recently developed a robust method for the preparation of bench-stable solutions of silicon Grignard reagents 1 (Scheme [1], bottom).[7] These had essentially been not available previously,[8] and we decided to assess their suitability as silicon nucleophiles in allylic substitution reactions, particularly with emphasis on the influence of the leaving group on the regioselectivity. Herein, we describe the application of silicon Grignard reagents to allylic substitution reactions catalyzed by manganese, iron, cobalt, nickel, copper, and palladium salts.

We started our investigation by exploring the coupling reaction of commercially available E-cinnamyl acetate [(E)-2a] and Me2PhSiMgX 1a (Table [1]). At the beginning, several first-row metal salts were employed as catalysts (5 mol%) without additional ligands (Table [1], entries 1–6). Any of these catalysts enabled the reaction, affording the linear allylic­ silane α-(E)-3a in near-quantitative yields using NiBr·glyme, CuI, and CuCN; however, MnBr2, FeCl3, and CoCl2­ furnished the desired product in somewhat lower yields. Also, (E)-2a underwent silylation in the presence of PdCl2 (entry 7). In all these reactions, the thermodynamically favored α-regioisomer was formed with high α/γ ratio. The yield remained high when 2 mol% of CuI were employed. A blank experiment without catalyst gave no conversion (entry 8).

Table 1 Selected Examples of the Catalyst Screeninga

Entry

Catalyst

E/Z of α-3a b

α/γb

Yield (%)b of 3a

1

MnBr2

99:1

96:4

67

2

FeCl3

99:1

98:2

79

3

CoCl2

99:1

99:1

81

4

NiBr2·glyme

99:1

98:2

94

5

CuI

99:1

99:1

95 (95)c

6

CuCN

99:1

99:1

95

7

PdCl2

97:3

95:5

80

8

none

trace

a Reactions performed on a 0.50 mmol scale.

b Yield is for the mixture of isomers and was determined by GLC analysis with tetracosane as an internal standard.

c With CuI (2 mol%).

With the ligand-free, copper-catalyzed procedure in hand, we probed the effect of various leaving groups [(E)-2ai → α-(E)-3a and γ-3a, Table [2]]. Next to model substrate (E)-2a, E-cinnamyl alcohols activated as carboxylate [as in (E)-2b], carbonates [as in (E)-2c and (E)-2d], carbamate [as in (E)-2e], and phosphate [as in (E)-2f] participated well in this silylation (Table [2], entries 1–6); yields were generally high and α/γ ratios and E/Z selectivities were good. Cinnamyl halides (E)-2g and (E)-2h were also included into the survey (entries 7 and 8), again leading to high yields but to slightly diminished regioselectivities. This outcome, that is α-selectivity for all tested leaving groups, stands in stark contrast to earlier findings in copper-catalyzed allylic substitution with Si–B compounds[3] and silicon zinc reagents[4] (see Scheme [1], top). As expected, the allylic substitution did not occur with free cinnamyl alcohol [(E)-2i] (entry 9).

Table 2 Investigation of Leaving Groupsa

Entry

LG

Substrate

E/Z of α-3a b

α/γb

Yield of 3a (%)b

1

OC(O)Me

(E)-2a

99:1

99:1

95

2

OC(O)Ph

(E)-2b

97:3

99:1

85

3

OC(O)OMe

(E)-2c

99:1

96:4

94

4

OC(O)OEt

(E)-2d

99:1

97:3

92

5

OC(O)NHPh

(E)-2e

99:1

99:1

88

6

OP(O)(OEt)2

(E)-2f

95:5

94:6

87

7

Cl

(E)-2g

96:4

91:9

91

8

Br

(E)-2h

97:3

96:4

93

9

OH

(E)-2i

trace

a Reactions performed on a 0.50 mmol scale.

b Yield is for the mixture of isomers and was determined by GLC analysis with tetracosane as an internal standard.

This allylic substitution was then applied to a variety of primary allylic precursors using Me2PhSiMgX 1a (Scheme [2]). In accordance with the previous observations (Tables 1 and 2), isomerically pure geranyl acetate (E)-4a and neryl acetate (Z)-4a reacted cleanly to produce allylic silanes α-(E)-8a and α-(Z)-8a, respectively, with exclusive preservation of the double bond geometry and excellent α/γ selectivity. Allylic bromide (E)-5h underwent silylation equally well, however, with reduced regio- and diastereoselectivities. As expected, simple primary allylic electrophiles such as 6a and 7h were converted into corresponding silylated products in good yields.

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Scheme 2 Copper-catalyzed allylic substitution of primary allylic precursors with silicon Grignard reagents. Yields are for the mixture of isomers, and regiochemical and diasteromeric ratios were confirmed by 1H NMR analysis.
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Scheme 3 Copper-catalyzed allylic substitution of secondary allylic precursors with silicon Grignard reagents. Yields are for the mixture of isomers, and regiochemical and diasteromeric ratios were confirmed by 1H NMR analysis.

Unlike primary allylic sources that engage in an SN pathway with high regiocontrol, the regiochemical situation is different for secondary substrates. Cyclic 13a was obtained in high yield starting from the secondary bromide 12h (Scheme [3], eq 1). Acyclic 14b was transformed into γ-(Z)-15a with excellent γ-selectivity, corresponding to an SN′ mechanism (Scheme [3], eq 2). Interestingly, the Z-isomer was formed predominantly, which is different from literature precedence.[4a] [9] To further distinguish between anti-SN′ and syn-SN′ mechanisms, cyclic allylic carboxylate syn-16a was synthesized and subjected to the standard condition (Scheme [3], eq 3).[10] Indeed, syn-16a was converted into anti-17a with complete inversion of the stereochemical information. This result is consistent with related copper-promoted allylic substitutions.[3f] [4a] [11]

Continuing with allyl methyl carbonate (18c), different silicon Grignard reagents 1 were subjected to the standard setup (Scheme [4]). Similar to Me2PhSiMgX 1a, yields are generally excellent for regularly used MePh2Si (from 1b) and Ph3Si (from 1c) as well as more hindered t-BuPh2Si (from 1d) and t-Bu(Me)PhSi (from 1e). The same result was obtained with heteroatom-substituted silicon nucleophile 1f, containing Tamao’s silicon anion.[12]

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Scheme 4 Copper-catalyzed allylic substitution of allylic precursor 18c with silicon Grignard reagents. Yields are for the mixture of isomers, and ratios were determined by 1H NMR analysis. a EtOH/NH4Cl added after reaction.

Considering the challenges associated with the construction of silicon-stereogenic silanes,[13] we attempted an enantioselective version of this allylic substitution in the presence of chiral ligands (Scheme [5]). The reaction of racemic t-Bu(Me)PhSiMgX 1e and allylic precursor 18c was chosen as a model reaction. Several catalytic systems were tested but neither led to the asymmetric induction at the silicon atom.

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Scheme 5 Attempted enantioselective allylic substitution of allylic carbonate 18c with t-Bu(Me)PhSiMgX (1e)

To summarize, we have disclosed here a practical method for the synthesis of allylic silanes from readily accessible allylic precursors and easy-to-handle silicon Grignard reagents. Several metal salts can promote this transformation in moderate to excellent yields without the need of added ligand. The leaving-group scope is broad, comprising the usual oxygen leaving groups as well as halides.

All reactions were performed in flame-dried glassware using conventional Schlenk techniques under a static pressure of N2, unless otherwise stated. Liquids and solutions were transferred with syringes. CuI (anhyd CuI, 99%, ABCR), other metal salts, and chiral ligands were purchased from commercial suppliers and used as received. Allylic precursors 2a, 2g, 2h, 2i, (E)-4a, (Z)-4a, 6a, 7h, 12h, and 18c are commercially available. Compounds 2b,[4c] 2c,[4c] 2e,[4c] 2f,[4c] (E)-5h,[4c] 14b,[14] and syn-16a [10] were synthesized according to the reported procedure, and all spectroscopic data matched those reported. THF was dried over Na or K/benzophenone and distilled prior to use. Technical grade solvents for extraction or chromatography (cyclohexane, CH2Cl2, EtOAc­, and n-pentane) were distilled prior to use. Analytical TLC was performed on silica gel 60 F254 glass plates from Merck. Flash column chromatography was performed on silica gel 60 (40–63 μm, 230–400 mesh, ASTM) from Grace using the indicated solvents. 1H, 13C, and 29Si DEPT NMR spectra were recorded in CDCl3 on Bruker AV400 and AV500 instruments. Chemical shifts are reported in parts per million (ppm) and are referenced to the residual solvent resonance as the internal standard (CHCl3: δ = 7.26 for 1H NMR and CDCl3: δ = 77.0 for 13C NMR). 29Si is referenced in compliance with the unified scale for NMR chemical shifts as recommended by the IUPAC stating the chemical shift relative to BF3·Et2O, CCl3F and Me4Si.[15] Data are reported as follows: chemical shift, multiplicity (standard abbreviations), coupling constant (Hz), and integration. Gas liquid chromatography (GLC) was performed on a Varian 430-GC gas chromatograph equipped with a Varian FactorFour Capillary column (30 m × 0.25 mm, 0.25 μm film thickness). Enantiomeric excesses were determined by analytical high-performance liquid chromatography (HPLC) analysis on an Agilent Technologies 1290 Infinity instrument with a chiral stationary phase using Daicel Chiralcel OJ-RH, (MeCN/H2O mixtures as solvent). Melting points were determined using a Leica Galen III melting point apparatus. Mass spectra (MS) were obtained from the Analytical Facility at the Institut für Chemie, Technische Universität Berlin.


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Preparation of R3SiMgX 1; General Procedure 1 (GP 1)

At 0 °C, the required chlorosilane (24.0 mmol, 1.0 equiv) was added to a flame-dried Schlenk flask charged with activated Li chunks (666 mg, 96.0 mmol, 4.0 equiv) suspended in THF (20 mL), and the resulting suspension was stirred at this temperature overnight under N2 atmosphere to give R3SiLi. The concentration of R3SiLi (~1.0 M in THF, approximately 80–90% conversion) was determined by titration against diphenylacetic acid (Kofron’s method).[16] A flame-dried two-necked round-bottomed flask charged with a magnetic stir bar and equipped with a water condenser is connected to a Schlenk line and purged with N2. The flask was charged with Mg turnings (292 mg, 12.0 mmol, 1.2 equiv) followed by the addition of THF (10 mL) and was then heated to 66 °C. 1,2-Dibromoethane (1.88 g, 10.0 mmol, 1.0 equiv) was quickly added via syringe, and the reaction mixture was heated at reflux for 3 h at high water-flow rate to afford MgBr2 (1.0 M in THF at 66 °C). Then, the corresponding R3SiLi solution (10 mmol, 1.0 equiv) was subsequently added dropwise to the MgBr2 solution over 10 min at this temperature. R3SiMgX·2LiX solution formed was cooled to r.t. The concentration of R3SiMgX·2LiX (~0.5 M in THF, full conversion) was determined by titration against I2 (Knochel­’s­ method).[17] The homogeneous R3SiMgX·2LiX solution could be stored in a Schlenk flask purged with N2 at 2–8 °C in a fridge.

The color of the R3SiMgX·2LiX solution depends on the substitution at the silicon atom: Me2PhSiMgX·2LiX 1a (purple), MePh2SiMgX·2LiX 1b (light purple), Ph3SiMgX·2LiX 1c (brown), t-BuPh2SiMgX·2LiX 1d (light green), t-Bu(Me)PhSiMgX·2LiX 1e (light purple), (Et2N)Ph2SiMgBr·2LiX 1f (gray).


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Copper-Catalyzed Allylic Substitution with R3SiMgX 1; General Procedure 2 (GP 2)

A flame-dried Schlenk flask equipped with a stir bar was charged with CuI (1.9 mg, 0.010 mmol, 2.0 mol%). The flask was evacuated and backfilled with N2 (3 ×) followed by the addition of THF (1 mL). After stirring for 10 min at r.t., the indicated allylic precursor (0.50 mmol, 1.0 equiv) was added, and the solution was brought to 0 °C. Then, the corresponding R3SiMgX 1 (0.60 mmol, 1.2 equiv) was added over 1 min. After 1 h, the reaction was quenched with sat. aq NH4Cl (5 mL). CH2Cl2 (20 mL) was added for extraction, and the CH2Cl2 layer was washed with brine (20 mL) and H2O (20 mL). The aqueous phase was extracted with CH2Cl2 (2 × 20 mL). The combined organic phases were dried (anhyd Na2SO4), filtered, and the solvents were evaporated under reduced pressure. Purification of the residue by flash column chromatography on silica gel with indicated solvent as eluent afforded the silylated product.

(E)-Cinnamyldimethyl(phenyl)silane [α-(E)-3a]

Prepared from (E)-cinnamyl acetate [(E)-2a; 88 mg, 0.50 mmol] according to GP 2 with Me2PhSiMgX 1a at 0 °C. Purification by flash column chromatography on silica gel using n-pentane afforded α-(E)-3a as a colorless oil; yield: 120 mg (95%, contaminated with 1,1,2,2-tetramethyl-1,2-diphenyldisilane); Rf = 0.60 (n-pentane).

1H NMR (500 MHz, CDCl3): δ = 0.31 (s, 6 H), 1.90 (d, J = 6.5 Hz, 2 H), 6.16–6.26 (m, 2 H), 7.12–7.17 (m, 1 H), 7.24–7.26 (m, 4 H), 7.35–7.38 (m, 3 H), 7.49–7.55 (m, 2 H).

13C NMR (125 MHz, CDCl3): δ = –3.3, 23.0, 125.6, 126.3, 127.1, 127.8, 128.4, 128.9, 129.1, 133.6, 138.4, 138.5.

29Si DEPT NMR (99 MHz, CDCl3): δ = –4.1.

HRMS (EI): m/z [M]+ calcd for C17H20Si: 252.1334; found: 252.1332.

The spectroscopic data are in accordance with those reported.[4c]


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(E)-Geranyldimethyl(phenyl)silane [α-(E)-8a]

Prepared from (E)-geranyl acetate [(E)-4a; 98 mg, 0.50 mmol] according to GP 2 with Me2PhSiMgX 1a at 0 °C. Purification by flash column chromatography on silica gel using n-pentane afforded α-(E)-8a as a colorless oil; yield: 119 mg (87%); Rf = 0.65 (n-pentane).

1H NMR (500 MHz, CDCl3): δ = 0.26 (s, 6 H), 1.50 (s, 3 H), 1.61 (s, 3 H), 1.64 (d, J = 8.6 Hz, 2 H), 1.69 (s, 3 H), 1.97–2.02 (m, 2 H), 2.03–2.10 (m, 2 H), 5.09 (tt, J = 6.7, 1.4 Hz, 1 H), 5.17 (tq, J = 8.6, 1.4 Hz, 1 H), 7.31–7.38 (m, 3 H), 7.49–7.55 (m, 2 H).

13C NMR (125 MHz, CDCl3): δ = –3.3, 15.8, 17.67, 17.69, 25.7, 26.9, 40.0, 119.6, 124.6, 127.7, 128.8, 131.2, 133.1, 133.6, 139.3.

29Si DEPT NMR (99 MHz, CDCl3): δ = –3.8.

HRMS (EI): m/z [M]+ calcd for C18H28Si: 272.1955; found: 272.1952.

The spectroscopic data are in accordance with those reported.[4a]


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(Z)-Neryldimethyl(phenyl)silane [α-(Z)-8a]

Prepared from (Z)-neryl acetate [(Z)-4a; 98 mg, 0.50 mmol] according to GP 2 with Me2PhSiMgX 1a at 0 °C. Purification by flash column chromatography on silica gel using n-pentane afforded α-(Z)-8a as a colorless oil; yield: 124 mg (91%); Rf = 0.65 (n-pentane).

1H NMR (500 MHz, CDCl3): δ = 0.26 (s, 6 H), 1.60 (s, 3 H), 1.65 (d, J = 8.6 Hz, 2 H), 1.69 (s, 6 H), 1.94–2.02 (m, 4 H), 5.07–5.13 (m, 1 H), 5.17 (t, J = 8.6 Hz, 1 H), 7.33–7.38 (m, 3 H), 7.49–7.54 (m, 2 H).

13C NMR (125 MHz, CDCl3): δ = –3.2, 17.3, 17.6, 23.4, 25.7, 26.4, 31.7, 119.7, 124.6, 127.7, 128.8, 131.4, 133.6, 133.9, 139.3.

29Si DEPT NMR (99 MHz, CDCl3): δ = –4.2.

HRMS (EI): m/z [M]+ calcd for C18H28Si: 272.1955; found: 272.1952.

The spectroscopic data are in accordance with those reported.[4a]


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(3-Cyclohexylallyl)dimethyl(phenyl)silane (9a)

Prepared from (E)-(3-bromoprop-1-en-1-yl)cyclohexane [(E)-5h; 102 mg, 0.50 mmol] according to GP 2 with Me2PhSiMgX 1a at 0 °C. Purification by flash column chromatography on silica gel using n-pentane afforded 9a as a colorless oil; yield: 116 mg (90%, mixture of all isomers). The ratio of different isomers was confirmed by 1H NMR analysis.

α-(E)-9a

Rf = 0.70 (n-pentane).

1H NMR (500 MHz, CDCl3): δ = 0.26 (s, 6 H), 1.03–1.25 (m, 5 H), 1.61–1.71 (m, 8 H), 5.19–5.25 (m, 1 H), 5.29–5.38 (m, 1 H), 7.33–7.37 (m, 3 H), 7.49–7.54 (m, 2 H).

13C NMR (125 MHz, CDCl3): δ = –3.4, 21.6, 26.1, 26.2, 33.5, 41.0, 122.7, 127.6, 128.8, 133.7, 136.0, 139.1.

29Si DEPT NMR (99 MHz, CDCl3): δ = –4.7.

HRMS (EI): m/z [M]+ calcd for C17H26Si: 258.1798; found: 258.1786.


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Prenyldimethy(phenyl)silane (α-10a)

Prepared from prenyl acetate (6a; 64 mg, 0.50 mmol) according to GP 2 with Me2PhSiMgX 1a at 0 °C. Purification by flash column chromatography on silica gel using n-pentane afforded α-10a as a colorless oil; yield: 97 mg (95%); Rf = 0.70 (n-pentane).

1H NMR (500 MHz, CDCl3): δ = 0.26 (s, 6 H), 1.50 (s, 3 H), 1.63 (d, J = 8.6 Hz, 2 H), 1.69 (s, 3 H), 5.16 (tt, J = 8.6, 1.4 Hz, 1 H), 7.31–7.38 (m, 3 H), 7.49–7.55 (m, 2 H).

13C NMR (125 MHz, CDCl3): δ = –3.2, 17.6, 17.7, 25.7, 119.3, 127.6, 128.8, 129.5, 133.6, 139.3.

29Si DEPT NMR (99 MHz, CDCl3): δ = –3.8.

HRMS (EI): m/z [M]+ calcd for C13H20Si: 204.1329; found: 204.1329.

The spectroscopic data are in accordance with those reported.[9]


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Dimethyl(2-methylallyl)(phenyl)silane (α-11a)

Prepared from 3-bromo-2-methylpropene (7h; 68 mg, 0.50 mmol) according to GP 2 with Me2PhSiMgX 1a at 0 °C. Purification by flash column chromatography on silica gel using n-pentane afforded α-11a as a colorless oil; yield: 82 mg (86%); Rf = 0.70 (n-pentane).

1H NMR (500 MHz, CDCl3): δ = 0.32 (s, 6 H), 1.62 (s, 3 H), 1.78 (s, 2 H), 4.47–4.50 (m, 1 H), 4.59–4.62 (m, 1 H), 7.32–7.39 (m, 3 H), 7.50–7.57 (m, 2 H).

13C NMR (125 MHz, CDCl3): δ = –2.9, 25.2, 25.7, 108.8, 127.7, 128.9, 133.6, 139.1, 143.3.

29Si DEPT NMR (99 MHz, CDCl3): δ = –5.0.

HRMS (EI): m/z [M]+ calcd for C12H18Si: 190.1172; found: 190.1164.

The spectroscopic data are in accordance with those reported.[18]


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Dimethyl(cyclohex-2-en-1-yl)(phenyl)silane (13a)

Prepared from 3-bromocyclohexene (12h; 81 mg, 0.50 mmol) according to GP 2 with Me2PhSiMgX 1a at 0 °C. Purification by flash column chromatography on silica gel using n-pentane afforded 13a as a colorless oil; yield: 91 mg (84%); Rf = 0.75 (n-pentane).

1H NMR (500 MHz, CDCl3): δ = 0.28 (s, 3 H), 0.29 (s, 3 H), 1.43–1.53 (m, 2 H), 1.63–1.70 (m, 1 H), 1.74–1.82 (m, 2 H), 1.88–2.03 (m, 2 H), 5.60–5.69 (m, 2 H), 7.31–7.39 (m, 3 H), 7.50–7.56 (m, 2 H).

13C NMR (125 MHz, CDCl3): δ = –4.8 (SiCH3), –4.6 (SiCH3), 22.5, 23.8, 25.0, 25.6, 125.9, 127.5, 127.7, 128.9, 133.9, 138.3.

29Si DEPT NMR (99 MHz, CDCl3): δ = –2.5.

HRMS (EI): m/z [M]+ calcd for C14H20Si: 216.1334; found: 216.1327.

The spectroscopic data are in accordance with those reported.[9]


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Dimethyl(but-2-en-1-yl)(phenyl)silane (15a)

Prepared from but-3-en-2-yl benzoate (14b; 88 mg, 0.50 mmol) according to GP 2 with Me2PhSiMgX 1a at 0 °C. Purification by flash column chromatography on silica gel using n-pentane afforded 15a as a colorless oil; yield: 87 mg (91%, mixture of all isomers). The ratio of different isomers was confirmed by 1H NMR analysis; Rf = 0.70 (n-pentane).


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γ-(Z)-15a

1H NMR (500 MHz, CDCl3): δ = 0.26 (s, 6 H), 1.51 (d, J = 6.0 Hz, 3 H), 1.73 (d, J = 8.6 Hz, 2 H), 5.34–5.43 (m, 2 H), 7.33–7.38 (m, 3 H), 7.46–7.57 (m, 2 H).

29Si DEPT NMR (99 MHz, CDCl3): δ = –3.8.


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γ-(E)-15a

1H NMR (500 MHz, CDCl3): δ = 0.29 (s, 6 H), 1.61–1.68 (m, 5 H), 5.25–5.46 (m, 2 H), 7.33–7.38 (m, 3 H), 7.46–7.57 (m, 2 H).

29Si DEPT NMR (99 MHz, CDCl3): δ = –4.6.

The spectroscopic data are in accordance with those reported.[9]


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anti-Dimethyl(5-methylcyclohex-2-en-1-yl)(phenyl)silane (anti-17a)

Prepared from syn-5-methylcyclohex-2-en-1-yl acetate (syn-16a; 77 mg, 0.50 mmol) according to GP 2 with Me2PhSiMgX 1a at 0 °C. Purification by flash column chromatography on silica gel using n-pentane afforded anti-17a as a colorless oil; yield: 109 mg (95%, mixture of all isomers). The ratio of different isomers was confirmed by 1H NMR analysis; Rf = 0.50 (n-pentane).

1H NMR (500 MHz, CDCl3): δ = 0.29 (s, 3 H), 0.30 (s, 3 H), 0.88 (d, J = 6.4 Hz, 3 H), 1.41–1.48 (m, 1 H), 1.58–1.72 (m, 3 H), 1.82–1.87 (m, 1 H), 2.01–2.07 (m, 1 H), 5.55–5.59 (m, 1 H), 5.61–5.65 (m, 1 H), 7.33–7.37 (m, 3 H), 7.49–7.54 (m, 2 H).

13C NMR (125 MHz, CDCl3): δ = –4.13 (SiCH3), –4.08 (SiCH3), 21.2, 24.9, 26.2, 31.2, 33.0, 124.3, 127.2, 127.7, 128.9, 133.9, 138.5.

29Si DEPT NMR (99 MHz, CDCl3): δ = –2.6.

HRMS (EI): m/z [M]+ calcd for C15H22Si: 230.1491; found: 230.1492.

The spectroscopic data are in accordance with those reported.[3f]


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Allyldimethyl(phenyl)silane (19a)

Prepared from allyl methyl carbonate (18c; 58 mg, 0.50 mmol) according to GP 2 with Me2PhSiMgX 1a at 0 °C. Purification by flash column chromatography on silica gel using n-pentane afforded 19a as a colorless oil; yield: 84 mg (95%); Rf = 0.65 (n-pentane).

1H NMR (500 MHz, CDCl3): δ = 0.29 (s, 6 H), 1.76 (d, J = 8.6 Hz, 2 H), 4.82–4.92 (m, 2 H), 5.73–5.83 (m, 1 H), 7.33–7.39 (m, 3 H), 7.49–7.55 (m, 2 H).

13C NMR (125 MHz, CDCl3): δ = –3.5, 23.7, 113.4, 127.7, 129.0, 133.6, 134.6, 138.7.

29Si DEPT NMR (99 MHz, CDCl3): δ = –4.7.

HRMS (EI): m/z [M]+ calcd for C11H16Si: 176.1021; found: 176.1018.

The spectroscopic data are in accordance with those reported.[18]


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Allyl(methyl)diphenylsilane (19b)

Prepared from allyl methyl carbonate (18c; 58 mg, 0.50 mmol) according to GP 2 with MePh2SiMgX 1b at 0 °C. Purification by flash column chromatography on silica gel using n-pentane afforded 19b as a colorless oil; yield: 108 mg (91%); Rf = 0.55 (n-pentane).

1H NMR (500 MHz, CDCl3): δ = 0.56 (s, 3 H), 2.08 (d, J = 8.6 Hz, 2 H), 4.85–4.95 (m, 2 H), 5.75–5.85 (m, 1 H), 7.33–7.40 (m, 6 H), 7.51–7.56 (m, 4 H).

13C NMR (125 MHz, CDCl3): δ = –4.8, 22.1, 114.2, 127.8, 129.2, 134.1, 134.5, 136.6.

29Si DEPT NMR (99 MHz, CDCl3): δ = –9.6.

HRMS (EI): m/z [M]+ calcd for C16H18Si: 238.1178; found: 238.1172.

The spectroscopic data are in accordance with those reported.[19]


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Allyltriphenylsilane (19c)

Prepared from allyl methyl carbonate (18c; 58 mg, 0.50 mmol) according to GP 2 with Ph3SiMgX 1c at 0 °C. Purification by flash column chromatography on silica gel using n-pentane afforded 19c as a white solid; yield: 134 mg (89%); mp 90.0–90.8 °C; Rf = 0.35 (n-pentane).

1H NMR (500 MHz, CDCl3): δ = 2.40 (d, J = 7.8 Hz, 2 H), 4.87–4.98 (m, 2 H), 5.81–5.92 (m, 1 H), 7.33–7.44 (m, 9 H), 7.50–7.55 (m, 6 H).

13C NMR (125 MHz, CDCl3): δ = 21.8, 115.1, 127.8, 129.5, 133.8, 134.6, 135.7.

29Si DEPT NMR (99 MHz, CDCl3): δ = –13.8.

HRMS (EI): m/z [M]+ calcd for C21H20Si: 300.1334; found: 300.1330.

The spectroscopic data are in accordance with those reported.[19]


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Allyl(tert-butyl)diphenylsilane (19d)

Prepared from allyl methyl carbonate (18c; 58 mg, 0.50 mmol) according to GP 2 with t-BuPh2SiMgX 1d at 0 °C. Purification by flash column chromatography on silica gel using n-pentane afforded 19d as a colorless oil; yield: 115 mg (82%); Rf = 0.65 (n-pentane).

1H NMR (500 MHz, CDCl3): δ = 1.07 (s, 9 H), 2.08 (dt, J = 8.6, 1.4 Hz, 2 H), 4.78–4.82 (m, 1 H), 4.88–4.93 (m, 1 H), 5.71–5.82 (m, 1 H), 7.33–7.41 (m, 6 H), 7.59–7.64 (m, 4 H).

13C NMR (125 MHz, CDCl3): δ = 18.5, 18.8, 27.9, 114.5, 127.5, 129.1, 134.4, 134.7, 136.0.

29Si DEPT NMR (99 MHz, CDCl3): δ = –5.2.

HRMS (EI): m/z [M]+ calcd for C19H24Si: 280.1642; found: 280.1636.

The spectroscopic data are in accordance with those reported.[20]


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Allyl(tert-butyl)(methyl)(phenyl)silane (19e)

Prepared from allyl methyl carbonate (18c; 58 mg, 0.50 mmol) according to GP 2 with t-Bu(Me)PhSiMgX 1e at 0 °C. Purification by flash column chromatography on silica gel using n-pentane afforded 19e as a colorless oil; yield: 99 mg (91%); Rf = 0.65 (n-pentane).

HPLC-analysis: OJ-RH (Dacial), MeCN/H2O = 65:35, 0.2 mL/min, λ = 210 nm, t R = 47.9, 51.1 min.

1H NMR (500 MHz, CDCl3): δ = 0.28 (s, 3 H), 0.90 (s, 9 H), 1.81–1.87 (m, 1 H), 1.93–1.99 (m, 1 H), 4.78–4.82 (m, 1 H), 4.86–4.92 (m, 1 H), 5.71–5.82 (m, 1 H), 7.31–7.44 (m, 3 H), 7.48–7.55 (m, 2 H).

13C NMR (125 MHz, CDCl3): δ = –8.6, 17.4, 18.7, 26.8, 113.6, 127.5, 128.9, 134.7, 135.0, 136.0.

29Si DEPT NMR (99 MHz, CDCl3): δ = 1.5.

HRMS (EI): m/z [M]+ calcd for C14H22Si: 218.1485; found: 218.1482.


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Allyl(ethoxy)diphenylsilane (19f)

Prepared from allyl methyl carbonate (18c; 58 mg, 0.50 mmol) according to GP 2 with (Et2N)Ph2SiMgX 1f at 0 °C. Afterwards, anhyd EtOH (1 mL) and NH4Cl (55 mg, 2.0 mmol) was added, and the reaction mixture was stirred overnight. Purification by flash column chromatography on silica gel using n-pentane afforded 19f as a colorless oil; yield: 115 mg (86%); Rf = 0.30 (n-pentane).

1H NMR (500 MHz, CDCl3): δ = 1.22 (t, J = 7.1 Hz, 3 H), 2.18 (dt, J = 7.8, 1.4 Hz, 2 H), 3.81 (q, J = 7.1 Hz, 2 H), 4.88–4.98 (m, 2 H), 5.80–5.90 (m, 1 H), 7.35–7.44 (m, 6 H), 7.59–7.64 (m, 4 H).

13C NMR (125 MHz, CDCl3): δ = 18.4, 21.9, 59.5, 115.0, 127.8, 129.9, 133.1, 134.70, 134.73.

29Si DEPT NMR (99 MHz, CDCl3): δ = –8.6.

HRMS (EI): m/z [M – C3H5]+ calcd for C14H15OSi: 227.0887; found: 227.0889.

The spectroscopic data are in accordance with those reported.[21]


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Supporting Information

  • References


    • For recent reviews, see:
    • 1a Denmark SE. Ambrosi A. Org. Process Res. Dev. 2015; 19: 982
    • 1b Yus M. González-Gόmez JC. Foubelo F. Chem. Rev. 2013; 113: 5595
    • 1c Chabaud L. James P. Landais Y. Eur. J. Org. Chem. 2004; 15: 3173

      For selected examples with Si–Si compounds, see:
    • 2a Hayashi T. Ohno A. Lu S.-j. Matsumoto Y. Fukuyo E. Yanagi K. J. Am. Chem. Soc. 1994; 116: 4221
    • 2b Moser R. Nishikata T. Lipshutz BH. Org. Lett. 2010; 12: 28
    • 2c Selander N. Paasch JR. Szabό KJ. J. Am. Chem. Soc. 2011; 133: 409
    • 2d Larsson JM. Szabό KJ. J. Am. Chem. Soc. 2013; 135: 443

      For selected examples with Si–B compounds, see:
    • 3a Vyas DJ. Oestreich M. Angew. Chem. Int. Ed. 2010; 49: 8513
    • 3b Delvos LB. Vyas DJ. Oestreich M. Angew. Chem. Int. Ed. 2013; 52: 4650
    • 3c Takeda M. Shintani R. Hayashi T. J. Org. Chem. 2013; 78: 5007
    • 3d Hazra CK. Irran E. Oestreich M. Eur. J. Org. Chem. 2013; 4903
    • 3e Delvos LB. Hensel A. Oestreich M. Synthesis 2014; 46: 2957
    • 3f Delvos LB. Oestreich M. Synthesis 2015; 47: 924

      For selected examples with silicon zinc reagents, see:
    • 4a Oestreich M. Auer G. Adv. Synth. Catal. 2005; 347: 637
    • 4b Schmidtmann ES. Oestreich M. Chem. Commun. 2006; 3643
    • 4c Vyas DJ. Oestreich M. Chem. Commun. 2010; 46: 568
    • 4d Hensel A. Oestreich M. Chem. Eur. J. 2015; 21: 9062

      For nucleophilic substitution of silicon electrophiles with allylic metal reagents, see:
    • 5a Lennon PJ. Mack DP. Thompson QE. Organometallics 1989; 8: 1121
    • 5b Murakami K. Yorimitsu H. Oshima K. J. Org. Chem. 2009; 74: 1415

      Other methods hinge on the silylation of 1,3-dienes or allenes or, more recently, involve formal C–H bond silylation:
    • 6a Suginome M. Ohmura T. Miyake Y. Mitani S. Ito Y. Murakami M. J. Am. Chem. Soc. 2003; 125: 11174
    • 6b Larsson JM. Zhao TS. Szabό KJ. Org. Lett. 2011; 13: 1888
    • 6c Miller ZD. Li W. Belderrain TR. Montgomery J. J. Am. Chem. Soc. 2013; 135: 15282
    • 6d MeAtee JR. Yap GP. A. Watson DA. J. Am. Chem. Soc. 2014; 136: 10166
    • 6e Nakai S. Matsui M. Shimizu Y. Adachi Y. Obora Y. J. Org. Chem. 2015; 80: 7317
  • 7 Xue W. Shishido R. Oestreich M. Angew. Chem. Int. Ed. 2018; 57: 12141
  • 8 George MV. Peterson DJ. Gilman H. J. Am. Chem. Soc. 1960; 82: 403
  • 9 Fleming I. Higgins D. Lawrence NJ. Thomas AP. J. Chem. Soc., Perkin Trans. 1 1992; 3331
  • 10 For the preparation of syn-16a, see: Watson ID. G. Yudin AK. J. Am. Chem. Soc. 2005; 127: 17516
  • 11 Fleming I. Thomas AP. J. Chem. Soc., Chem. Commun. 1986; 1456
  • 12 Tamao K. Kawachi A. Ito K. J. Am. Chem. Soc. 1992; 82: 3989

    • For recent reviews on the synthesis of silicon-stereogenic silanes, see:
    • 13a Xu L.-W. Angew. Chem. Int. Ed. 2012; 51: 12932
    • 13b Cui Y.-M. Lin Y. Xu L.-W. Coord. Chem. Rev. 2017; 330: 37
    • 13c Shintani R. Synlett 2018; 29: 388
  • 14 Yasui K. Fugami K. Tanaka S. Tamaru Y. J. Org. Chem. 1995; 60: 1365
  • 15 Harris RK. Becker ED. Cabral de Menezes R. Goodfellow SM. Granger P. Pure Appl. Chem. 2001; 73: 1795
  • 16 Kofron WG. Baclawski LM. J. Org. Chem. 1976; 41: 1879
  • 17 Krasovskiy A. Knochel P. Synthesis 2006; 890
  • 18 Fleming I. Rowley M. Cuadrado P. González-Nogal AM. Pulido FJ. Tetrahedron 1989; 45: 413
  • 19 Li Z. Yang C. Zheng H. Qiu H. Lai G. J. Organomet. Chem. 2008; 693: 3771
  • 20 Barbero A. Cuadrado P. Gonzalez AM. Pulido FJ. Fleming I. J. Chem. Soc., Perkin Trans. 1 1991; 2811
  • 21 Jorapur YR. Shimada T. Synlett 2012; 23: 1633

  • References


    • For recent reviews, see:
    • 1a Denmark SE. Ambrosi A. Org. Process Res. Dev. 2015; 19: 982
    • 1b Yus M. González-Gόmez JC. Foubelo F. Chem. Rev. 2013; 113: 5595
    • 1c Chabaud L. James P. Landais Y. Eur. J. Org. Chem. 2004; 15: 3173

      For selected examples with Si–Si compounds, see:
    • 2a Hayashi T. Ohno A. Lu S.-j. Matsumoto Y. Fukuyo E. Yanagi K. J. Am. Chem. Soc. 1994; 116: 4221
    • 2b Moser R. Nishikata T. Lipshutz BH. Org. Lett. 2010; 12: 28
    • 2c Selander N. Paasch JR. Szabό KJ. J. Am. Chem. Soc. 2011; 133: 409
    • 2d Larsson JM. Szabό KJ. J. Am. Chem. Soc. 2013; 135: 443

      For selected examples with Si–B compounds, see:
    • 3a Vyas DJ. Oestreich M. Angew. Chem. Int. Ed. 2010; 49: 8513
    • 3b Delvos LB. Vyas DJ. Oestreich M. Angew. Chem. Int. Ed. 2013; 52: 4650
    • 3c Takeda M. Shintani R. Hayashi T. J. Org. Chem. 2013; 78: 5007
    • 3d Hazra CK. Irran E. Oestreich M. Eur. J. Org. Chem. 2013; 4903
    • 3e Delvos LB. Hensel A. Oestreich M. Synthesis 2014; 46: 2957
    • 3f Delvos LB. Oestreich M. Synthesis 2015; 47: 924

      For selected examples with silicon zinc reagents, see:
    • 4a Oestreich M. Auer G. Adv. Synth. Catal. 2005; 347: 637
    • 4b Schmidtmann ES. Oestreich M. Chem. Commun. 2006; 3643
    • 4c Vyas DJ. Oestreich M. Chem. Commun. 2010; 46: 568
    • 4d Hensel A. Oestreich M. Chem. Eur. J. 2015; 21: 9062

      For nucleophilic substitution of silicon electrophiles with allylic metal reagents, see:
    • 5a Lennon PJ. Mack DP. Thompson QE. Organometallics 1989; 8: 1121
    • 5b Murakami K. Yorimitsu H. Oshima K. J. Org. Chem. 2009; 74: 1415

      Other methods hinge on the silylation of 1,3-dienes or allenes or, more recently, involve formal C–H bond silylation:
    • 6a Suginome M. Ohmura T. Miyake Y. Mitani S. Ito Y. Murakami M. J. Am. Chem. Soc. 2003; 125: 11174
    • 6b Larsson JM. Zhao TS. Szabό KJ. Org. Lett. 2011; 13: 1888
    • 6c Miller ZD. Li W. Belderrain TR. Montgomery J. J. Am. Chem. Soc. 2013; 135: 15282
    • 6d MeAtee JR. Yap GP. A. Watson DA. J. Am. Chem. Soc. 2014; 136: 10166
    • 6e Nakai S. Matsui M. Shimizu Y. Adachi Y. Obora Y. J. Org. Chem. 2015; 80: 7317
  • 7 Xue W. Shishido R. Oestreich M. Angew. Chem. Int. Ed. 2018; 57: 12141
  • 8 George MV. Peterson DJ. Gilman H. J. Am. Chem. Soc. 1960; 82: 403
  • 9 Fleming I. Higgins D. Lawrence NJ. Thomas AP. J. Chem. Soc., Perkin Trans. 1 1992; 3331
  • 10 For the preparation of syn-16a, see: Watson ID. G. Yudin AK. J. Am. Chem. Soc. 2005; 127: 17516
  • 11 Fleming I. Thomas AP. J. Chem. Soc., Chem. Commun. 1986; 1456
  • 12 Tamao K. Kawachi A. Ito K. J. Am. Chem. Soc. 1992; 82: 3989

    • For recent reviews on the synthesis of silicon-stereogenic silanes, see:
    • 13a Xu L.-W. Angew. Chem. Int. Ed. 2012; 51: 12932
    • 13b Cui Y.-M. Lin Y. Xu L.-W. Coord. Chem. Rev. 2017; 330: 37
    • 13c Shintani R. Synlett 2018; 29: 388
  • 14 Yasui K. Fugami K. Tanaka S. Tamaru Y. J. Org. Chem. 1995; 60: 1365
  • 15 Harris RK. Becker ED. Cabral de Menezes R. Goodfellow SM. Granger P. Pure Appl. Chem. 2001; 73: 1795
  • 16 Kofron WG. Baclawski LM. J. Org. Chem. 1976; 41: 1879
  • 17 Krasovskiy A. Knochel P. Synthesis 2006; 890
  • 18 Fleming I. Rowley M. Cuadrado P. González-Nogal AM. Pulido FJ. Tetrahedron 1989; 45: 413
  • 19 Li Z. Yang C. Zheng H. Qiu H. Lai G. J. Organomet. Chem. 2008; 693: 3771
  • 20 Barbero A. Cuadrado P. Gonzalez AM. Pulido FJ. Fleming I. J. Chem. Soc., Perkin Trans. 1 1991; 2811
  • 21 Jorapur YR. Shimada T. Synlett 2012; 23: 1633

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Scheme 1 Copper-catalyzed allylic substitution with silicon (pro)nucleophiles (top; LG: leaving group) and preparation of silicon Grignard reagents (bottom)
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Scheme 2 Copper-catalyzed allylic substitution of primary allylic precursors with silicon Grignard reagents. Yields are for the mixture of isomers, and regiochemical and diasteromeric ratios were confirmed by 1H NMR analysis.
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Scheme 3 Copper-catalyzed allylic substitution of secondary allylic precursors with silicon Grignard reagents. Yields are for the mixture of isomers, and regiochemical and diasteromeric ratios were confirmed by 1H NMR analysis.
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Scheme 4 Copper-catalyzed allylic substitution of allylic precursor 18c with silicon Grignard reagents. Yields are for the mixture of isomers, and ratios were determined by 1H NMR analysis. a EtOH/NH4Cl added after reaction.
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Scheme 5 Attempted enantioselective allylic substitution of allylic carbonate 18c with t-Bu(Me)PhSiMgX (1e)