English

• 1.   Introduction

  gem-Diboronates as novel dimetalated compounds are highly valuable building blocks in organic synthesis due to their selective mono- or di-functionalization.^[1] Among them, the internal gem-diboronates are particular attractive for the construction of quaternary carbon centres.^{[1a, 1b, 2]} The non-catalytic cross-coupling of internal gem-diborona- tes with electrophiles (eg. halides and N-heteroaromatic N-oxides) and the addition reaction of internal gem-di- boronates with vinyl, carbonyl and carboxylic derivatives have been proven to be an ideal methodology for C—C bond formation. Most of these reactions proceed through the α-monoboryl carbanion which was generated by base promoted monodeborylation of gem-diboronates.^{[1e, 2b, 3]} Furthermore, the transition metal catalyzed cross coupling of one boron group of internal gem-diboro- nates with halides was an efficient method to construct mono boronic ester compounds, which could be further functionalized under appropriate reaction conditions.^{[1c, 4]} Meanwhile, the C—B bond of internal gem-diboronates could be transformed to C—F bond to achieve gem- difluorides through the deboronofluorination.^[5] In addition to the C—B bond transformation, the typical 1, 2-metalate rearrangement of boron was the other reaction mode of the internal gem-diboronates.^[6] Although internal gem-diboronates have been deemed as attractive bifunctional reagents, the methods to access this kind of compounds are still limited. Early synthetic methods of deprotonation-alkylation of 1, 1-dibornates^{[1c, 1p, 1q, 1ag, 3b, 7]} and alkylation of 1, 1, 1-tri- (boronates)^[8] could lead to internal gem-diboronates. However, the preparation of such start materials are complicated. Moreover, the alkylarenes, ^[8] gem-dihaloal- kanes, ^[6] alkynes, ^[9] vinylboronates^[10] and fully substituted benzylic lithiated carbamates^[3a] have been also successfully applied to afford internal gem-diboronates. Furthermore, the strategies of direct diborylation of N-tosylhydro- drazones^[11] (Scheme 1a) or diazoalkanes^[12] (Scheme 1b) which pre-prepared form their corresponding ketones were also used to achieve the gem-diboronates (Scheme 1b). Compared to these reported methods, direct deoxygenative gem-diborylation of widely available ketones to access internal gem-diboronates would be more attractive. In 2017, our group reported an ICyCuCl (ICy＝1, 3-dicyclohexylimidazol-2-ylidene) catalyzed deoxygenative diborylation of ketones to prepare these internal gem-diboronates (Scheme 1c).^[13] Although various internal gem-diboronates could be well synthesized, the use of expensive NHC ligand ICy and the pre-preparation of ICyCuCl catalyst promoted us to further optimize this catalytic system with more practical and economical catalyst for this transformation.

  Scheme 1

  

  Scheme 1.  Methods for the synthesis of internal gem-diboro- nates from ketones

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  2.   Result and discussion

  Recently, our group have developed an iron catalyzed deoxygenative diborylation of aldehydes to synthesize corresponding gem-diboronates with B₂pin₂ as boron source, in which the addition of Fe-Bpin species to carbonyl group of aldehyde was assumed to be the crucial step.^[14] Inspired by our previous studies, the deoxygenative diborylation reaction of ketones with the iron catalytic system was examined. 4-Phenylbutan-2-one (1a) was first selected as the model substrate and toluene was used as solvent. After considerable efforts, the reaction was achieved by using the following optimal conditions: B₂pin₂ (2.8 equiv.), FeBr₂ (10 mol%), NaO^tBu (1.3 equiv.) in toluene at 100 ℃ (Table 1, Entry 1). As shown in Table 1, the pre-catalyst has the crucial effects on the formation of gem-diboronates. Among all the catalysts tested, FeBr₂ showed the best reactivity (Entries 2~4). And it should be emphasized that the necessity for iron has been confirmed by the result that no desired internal gem-diborylation product has been achieved in the absence of FeBr₂ (Entry 5). In these reaction conditions, the amount of NaO^tBu also played a key role. Catalytic amounts of NaO^tBu (40 mol%) could only resulted in trace amount of 2a formation (Entry 6). However, the α-OH Boronate species which was generated by the borylation of ketone was observed. And the excess of NaO^tBu (2.0 and 3.0 equiv.) would supress the formation of the desired compound 2a (Entries 7 and 8).

  Table 1

  

  Table 1.  Reaction parameters of the deoxygenative gem- diborylation of ketones^a

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  Entry	Variation from "standard conditions"	Yieldb/%
  1	None	73
  2	FeF2 instead of FeBr2	14
  3	FeCl2 instead of FeBr2	39
  4	Fe(OAc)2 instead of FeBr2	59
  5	No FeBr2	n.d.
  6	NaOtBu (0.4 equiv.)	Trace
  7	NaOtBu (2.0 equiv.)	59
  8	NaOtBu (3.0 equiv.)	32
  a Conditions: 1a (0.5 mmol), B2pin2 (2.8 equiv. 1.4 mmol), NaOtBu (1.3 equiv., 0.65 mmol), catalyst (10 mol%, 0.05 mmol), toluene (3.0 mL), 100 ℃, 5 h; b Determined by gas chromatography (GC) analysis using naphthalene as the internal standard.

  With the optimized conditions in hand, the substrates scope of this protocol have been explored (Table 2). Various of simple aliphatic ketones such as 4-phenylbutan-2- one, 2-pentanone and 3-pentanone proceeded smoothly to afford the corresponding internal gem-diboronates in moderate to good yields under this condition (2a, 2u and 2v). Notably, substrates bearing ketal (2r, 2s) and alkene (2t) group proceeded well to give the desired products with sufficient yields. Substrates such as piperonyl acetone, 2-tetralone, 7-methoxy-2-tetralone and indan-2-one were well gem-diborylated to afford their desired products (2b, 2o, 2p and 2q). Cyclic ketones such as five-membered ring, six-membered ring and seven-membered ring were all compatible in this reaction (2h~2n). Sterically demanding substrates containing an ortho substituent, proceeded smoothly to give the corresponding deoxygenative gem- diboronates 2i in yield of 40%. Aryl C-Cl group was also suitable with this protocol (2d), and provided a potential for further transformation. Aryl C-CF₃, and aromatic methoxyl group were also tolerant to afford the target com-pounds (2e~2g). Acetone-d₆ was also used to prepare corresponding deuteration internal gem-diboronates (2w) in 47% yield.

  Table 2

  

  Table 2.  Substrates scope of the iron catalyzed deoxygenative diborylation of ketones^a

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  a Conditions: 1 (1.0 mmol), B2pin2 (2.8 equiv. 2.8 mmol), NaOtBu (1.3 equiv. 1.3 mmol), FeBr2 (10 mol%, 0.1 mmol), toluene (5.0 mL), 100 ℃ for 5 h in N2 atmosphere, yields are based on isolated products; b 0.5 mmol scale, toluene (3.0 mL); c B2pin2 (2.0 mmol), NaOtBu (1.5 mmol).

  To demonstrate the practical applicability of this transformation, the 10.0 mmol scale reactions of 1s were carried out under standard conditions. As a result, 2.60 g (60% yield) of 2s were isolated, indicating the possibility to scale up this procedure (Scheme 2).

  Scheme 2

  

  Scheme 2.  Gram scale synthesis of internal gem-diboronates

  Conditions and regents: 1s (10.0 mmol), B₂pin₂ (2.8 equiv. 28.0 mmol), NaO^tBu (1.3 equiv. 13.0 mmol), FeBr₂ (10 mol%, 1.0 mmol), toluene (50.0 mL), 100 ℃ for 5 h in N₂ atmosphere. Yields are based on isolated products

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  As above mentioned, internal gem-diboronates could be used as a building block to construct quaternary carbon centres through the transformation of C—B bond to C—C bond. Herein, the C—C bond formation reactions were explored by using this compounds. Initially, acetone, the common organic solvent, was gem-diborylated to afford internal gem-diboronate 2wa under the standard conditions (Scheme 3). Then, some modes of transformation of 2wa has been applied. Tertiary boronic ester 3a has been prepared in yield of 83% in the presence of internal gem-diboronates 2wa and 1-bromooctane via deborylative borylalkylation process.^[11] Compound 4a, which containing a quandary carbon centres could also be achieved by the coupling reaction of 3a with 2-bromothiophene.^[15] Furthermore, 1, 4-dione 3b has also been synthesized by dual-functionalization of 2wa through the deoxygenative enolization with carboxylic acid and methyl bromoacetate.^[1e]

  Scheme 3

  

  Scheme 3.  Further application of internal gem-diboronates

  Reaction conditions: (a) 2wa (0.39 mmol), 1-bromoocatane (0.3 mmol), NaO^tBu (0.9 mmol), THF, r.t., 12 h; (b) 2wa (0.375 mmol), MeLi (0.625 mmol, 1.6 mol/L in diethyl ether), benzoic acid (0.25 mmol), methyl bromoacetate (0.5 mmol), THF; (c) 2-bromothiophene (0.36 mmol), ⁿBuLi (0.36 mmol, 1.6 mol/L in hexanes), 3a (0.3 mmol), NBS (0.36 mmol), THF.

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  Based on the previous reports^[16] and our works, ^{[13, 14]} the reaction pathway was proposed (Scheme 4). Initially, 'ate' complex 5, which was generated by interaction of NaO^tBu with B₂pin₂, reacted with FeBr₂ to generate iron boryl species 6. Then the ketones inserted into the Fe—B bond of 6 to afford complex 7. Subsequently, σ-bond metathesis with B₂pin₂ occurred to afford the α-OBpin boronates 9 and regenerated 6. The α-OBpin boronates 9 could interact with NaO^tBu to generate 10, followed by the reaction with B₂pin₂ to afford adduct 11. Then the intramolecular transfer of the boryl group occurred to produce tetracoordinate boryl species 12, which underwent 1, 2-migration to afford the final internal gem-diboronates 2.

  Scheme 4

  

  Scheme 4.  Proposed reaction mechanism

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  3.   Conclusions

  In summary, a Fe-catalyzed/ base-promoted deoxygenative diborylation of ketones was demonstrated. Various aliphatic ketones were gem-diborylated under current reaction conditions. More importantly this novel strategy shows great potential in synthetic chemistry through the gram scale experiments and the elaboration of the final internal gem-diboronate products.

  4.   Experimental Section

  4.1   General information

  All reactions were isolated from moisture and oxygen by a nitrogen atmosphere with a sealed tube. All glassware was oven dried at 110 ℃ for hours and cooled down under vacuum. Toluene was purified using Pure Solv 7-SDS solvent drying system. Unless otherwise noted, materials were obtained from commercial suppliers and used without further purification. Thin layer chromatography (TLC) employed glass 0.25 mm silica gel plates. Flash chromatography columns were packed with 100~200 mesh silica gel or through SepaBeamTM Machine SPB-3006012. Gas chromatographic analyses were performed on a GC-2010 Plus gas chromatography instrument with an FID detector. GC-MS spectra were recorded on a GCMS-QP2010 SE. The High Resolution MS analyses were performed on an Agilent 6530 Accurate-Mass Q-TOF LC/MS with ESI mode. NMR spectra were recorded on a 400 MHz for ¹H NMR and 101 MHz for ¹³C NMR, using tetramethylsilane as an internal reference and CDCl₃ as the solvent. Chemical shift values for protons were reported downfield from tetramethylsilane and were referenced to residual proton of TMS. Carbon nuclear magnetic resonance spectra (¹³C NMR) were recorded at 101 MHz. Chemical shifts for carbons were reported downfield from tetramethylsilane and were referenced to the carbon resonance of CDCl₃ (δ 77.0). The boron-bound carbon was not detected due to quadrupolar relaxation.

  4.2   General procedure for the synthesis of internal gem-diboroates compounds

  In glove box, a 25 mL resealable reaction tube of solvent flask equipped with a stirrer bar was charged with NaO^tBu (124.9 mg, 1.3 mmol), B₂pin₂ (711.2 mg, 2.8 mmol), FeBr₂ (21.6 mg, 0.1 mmol), and 5 mL of toluene. The tube was sealed with a Teflon screw cap and taken out of the glove box. The mixture was stirred at room temperature for 5 min. Subsequently, ketone (1.0 mmol) was added under nitrogen atmosphere. Then, the tube was sealed and the mixture was heated at 100 ℃ with stirring for 5 h. Upon completion, ethyl acetate was added to the mixture to quench the reaction. The pure product was obtained by flash column chromatography on silica gel.

  2, 2'-(4-Phenylbutane-2, 2-diyl)bis(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane) (2a):^[12b] White solid, 265.4 mg, 69% yield. m.p. 104~105 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.26~7.18 (m, 4H), 7.15~7.11 (m, 1H), 2.60~2.56 (m, 2H), 1.85~1.80 (m, 2H), 1.23 (s, 24H), 1.16 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 143.8, 128.5, 128.1, 125.3, 82.9, 36.7, 34.2, 24.7, 24.6, 16.0.

  2, 2'-(4-(Benzo[d][1, 3]dioxol-5-yl)butane-2, 2-diyl)bis-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane) (2b): White solid, 267.9 mg, 62% yield. m.p. 129~130 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 6.72~6.63 (m, 3H), 5.89 (s, 2H), 2.51~2.47 (m, 2H), 1.80~1.76 (m, 2H), 1.23 (s, 24H), 1.13 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 147.3, 145.3, 137.8, 121.1, 109.1, 107.9, 100.6, 83.0, 37.0, 34.0, 24.8, 24.6, 16.0; HRMS (ESI) calcd for C₂₃H₃₆B₂O₆Na [M+ Na]⁺ 453.2596, found 453.2600.

  2, 2'-(4-(4-Methoxyphenyl)butane-2, 2-diyl)bis(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane) (2c): White solid, 257.7 mg, 62% yield. m.p. 108~109 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.11 (d, J＝8.4 Hz, 2H), 6.79 (d, J＝8.4 Hz, 2H), 3.75 (s, 3H), 2.52 (t, J＝8.8 Hz, 2 H), 1.80 (t, J＝8.8 Hz, 2H), 1.22 (s, 24H), 1.15 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 157.4, 135.7, 129.2, 113.4, 82.8, 55.0, 36.8, 33.1, 24.6, 24.5, 15.9; HRMS (ESI) calcd for C₂₃H₃₈B₂- O₅Na [M+Na]⁺ 439.2803, found 439.2808.

  2, 2'-(1-(4-Chlorophenyl)propane-2, 2-diyl)bis(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane) (2d): White solid, 288.6 mg, 71% yield. m.p. 79~80 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.20~7.15 (m, 4H), 2.84 (s, 2H), 1.23 (s, 12H), 1.20 (s, 12H), 0.98 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 140.2, 131.2(3), 131.1(7), 127.6, 83.1, 38.5, 24.8, 24.6, 15.8; HRMS (ESI) calcd for C₂₁H₃₃B₂ClO₄Na [M+Na]⁺ 429.2151, found 429.2158.

  2, 2'-(1-(3, 4-Dimethoxyphenyl)propane-2, 2-diyl)bis-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane) (2e): Colorless oil, 174.9 mg, 40% yield. ¹H NMR (400 MHz, CDCl₃) δ: 6.82~6.72 (m, 3H), 3.85 (s, 3H), 3.83 (s, 3H), 2.83 (s, 2H), 1.24 (s, 12H), 1.20 (s, 12H), 1.03 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 148.0, 146.9, 134.3, 121.8, 113.6, 110.5, 83.0, 55.7, 55.6, 38.7, 24.8, 24.5, 15.9; HRMS (ESI) calcd for C₂₃H₃₈B₂O₆Na [M+Na]⁺ 455.2752, found 455.2757.

  2, 2'-(1-(3-(Trifluoromethyl)phenyl)propane-2, 2-diyl)bis-(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane) (2f): Colorless oil, 262.2 mg, 60% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.61~7.60 (m, 1H), 7.41~7.38 (m, 2H), 7.33~7.29 (m, 1H), 2.93 (s, 2H), 1.24 (s, 12H), 1.20 (s, 12H), 1.00 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 142.7, 133.5, 130.0 (q, J＝31.6 Hz), 127.8, 126.5 (q, J＝3.8 Hz), 124.5 (q, J＝273.7 Hz), 122.4 (q, J＝3.9 Hz), 83.3, 39.1, 24.8, 24.5, 15.8; HRMS (ESI) calcd for C₂₂H₃₃B₂F₃O₄Na [M+Na]⁺ 463.2415, found 463.2417.

  2, 2'-(1-(4-Methoxyphenyl)propane-2, 2-diyl)bis(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane) (2g):^[13] White solid, 220.5 mg, 55% yield. m.p. 69~70 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.16 (d, J＝8.0 Hz, 2H), 6.75 (d, J＝8.0 Hz, 2H), 3.75 (s, 3H), 2.82 (s, 2 H), 1.23 (s, 12H), 1.20 (s, 12H), 0.98 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 157.5, 133.8, 130.7, 112.9, 83.0, 55.0, 38.2, 24.7, 24.6, 15.8.

  2, 2'-(Cyclopentane-1, 1-diyl)bis(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane) (2h):^[11a] White solid, 130.2 mg, yield 40%. m.p. 50~51 ℃(lit.^[11a] m.p. 52~53 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 1.81 (t, J＝6.8 Hz, 4H), 1.53~1.49 (m, 4H), 1.22 (s, 24H); ¹³C NMR (101 MHz, CDCl₃) δ: 82.8, 30.5, 27.2, 24.5.

  2, 2'-(2-Methylcyclopentane-1, 1-diyl)bis(4, 4, 5, 5-tetra-methyl-1, 3, 2-dioxaborolane) (2i): Colorless oil, 135.6 mg, 40% yield. ¹H NMR (400 MHz, CDCl₃) δ: 2.44~2.36 (m, 1H), 1.95~1.81 (m, 2H), 1.74~1.60 (m, 2H), 1.53~1.42 (m, 1H), 1.23~1.20 (m, 25H), 0.98 (d, J＝6.8 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 82.7(2), 82.7(0), 38.2, 35.5, 28.8, 24.8, 24.6, 24.4, 19.6; HRMS (ESI) calcd for C₁₈H₃₄B₂O₄Na [M+Na]⁺ 359.2541, found 359.2545.

  2, 2'-(Cyclohexane-1, 1-diyl)bis(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane) (2j): White solid, 111.3 mg, 66% yield. m.p. 59~60 ℃ (lit.^[11a] 59~60 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 1.66~1.63 (m, 4H), 1.45~1.37 (m, 6H), 1.22 (s, 24H); ¹³C NMR (101 MHz, CDCl₃) δ: 82.7, 29.5, 26.7, 26.4, 24.

  2, 2'-(4-Methylcyclohexane-1, 1-diyl)bis(4, 4, 5, 5-tetra-methyl-1, 3, 2-dioxaborolane) (2k): White solid, 191.6 mg, 55% yield. m.p. 45~46 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 2.02~1.96 (m, 2H), 1.63~1.58 (m, 2H), 1.38~1.18 (m, 27H), 0.98~0.87 (m, 2H), 0.82 (d, J＝6.4 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 82.9, 82.7, 35.1, 32.5, 29.2, 24.7, 24.6, 23.0; HRMS (ESI) calcd for C₁₉H₃₆B₂O₄Na [M+Na]⁺ 373.2697, found 373.2702.

  2, 2'-(3-Methylcyclohexane-1, 1-diyl)bis(4, 4, 5, 5-tetra-methyl-1, 3, 2-dioxaborolane) (2l): White solid, 217.8 mg, 62% yield. m.p. 57~58 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 1.96~1.93 (m, 2H), 1.62~1.56 (m, 2H), 1.37~1.26 (m, 3H), 1.21 (s, 12H), 1.18 (s, 12H), 0.95~0.89 (m, 1H), 0.82 (d, J＝6.4 Hz, 3H), 0.78~0.71 (m, 1H); ¹³C NMR (101 MHz, CDCl₃) δ: 82.7, 82.5, 37.8, 35.3, 32.1, 28.8, 26.3, 24.5(4), 24.4(9), 24.4(5), 23.2; HRMS (ESI) calcd for C₁₉H₄₀B₂NO₄ [M+NH₄]⁺ 368.3143, found 368.3146.

  2, 2'-(Cycloheptane-1, 1-diyl)bis(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane) (2m): White solid, 185.4 mg, 53% yield. m.p. 36~37 ℃ (lit.^[11a] 36~37 ℃); ¹H NMR (400 MHz, CDCl₃) δ: 1.82~1.79 (m, 4H), 1.60~1.57 (m, 4H), 1.51~1.49 (m, 4H), 1.23 (s, 24H); ¹³C NMR (101 MHz, CDCl₃) δ: 82.7, 31.6, 28.9, 27.8, 24.6.

  2, 2'-(4-Phenylcyclohexane-1, 1-diyl)bis(4, 4, 5, 5-tetra-methyl-1, 3, 2-dioxaborolane) (2n): White solid, 265.7 mg, 64% yield. m.p. 90~91 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.28~7.13 (m, 5H), 2.46~2.40 (m, 1H), 2.17~2.15 (m, 2H), 1.84~1.83 (m, 2H), 1.54~1.46 (m, 4H), 1.28 (s, 12H), 1.22 (s, 12H); ¹³C NMR (101 MHz, CDCl₃) δ: 148.4, 128.2, 126.8, 125.7, 83.1, 82.9, 44.5, 34.1, 29.7, 24.8, 24.7; HRMS (ESI) calcd for C₂₄H₃₈B₂O₄Na [M+ Na]⁺ 435.2854, found 435.2859.

  2, 2'-(1, 2, 3, 4-Tetrahydronaphthalene-2, 2-diyl)bis(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane) (2o):^[13] White solid, 274.9 mg, 72% yield. m.p. 106~107 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.14~7.05 (m, 4H), 2.99 (s, 2H), 2.89 (t, J＝6.6 Hz, 2H), 2.05 (t, J＝6.6 Hz, 2H), 1.22 (s, 12H), 1.19 (s, 12H); ¹³C NMR (101 MHz, CDCl₃) δ: 138.2, 136.7, 128.9, 128.8, 125.0, 124.8, 83.0, 32.6, 28.0, 26.0, 24.5, 24.4.

  2, 2'-(7-Methoxy-1, 2, 3, 4-tetrahydronaphthalene-2, 2-diyl)bis(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane) (2p): White solid, 243.8 mg, 59% yield. m.p. 98~99 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 6.90 (d, J＝8.0 Hz, 1H), 6.64~6.60 (m, 2H), 3.74 (s, 3H), 2.90 (s, 2H), 2.75 (t, J＝6.6 Hz, 2H), 1.97 (t, J＝6.4 Hz, 2H), 1.17 (s, 12H), 1.14 (s, 12H); ¹³C NMR (101 MHz, CDCl₃) δ: 156.8, 139.1, 129.6, 128.8, 113.3, 111.5, 82.9, 55.0, 32.9, 27.2, 26.2, 24.4(2), 24.4(0); HRMS (ESI) calcd for C₂₃H₄₀B₂NO₅ [M+NH₄]⁺ 432.3093, found 432.3097.

  2, 2'-(2, 3-Dihydro-1H-indene-2, 2-diyl)bis(4, 4, 5, 5-tetra-methyl-1, 3, 2-dioxaborolane) (2q):^[13] Pale yellow solid, 59.3 mg, 32% yield. m.p. 109~110 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 7.18~7.16 (m, 2H), 7.08~7.06 (m, 2H), 3.23 (s, 4H), 1.18 (s, 24H); ¹³C NMR (101 MHz, CDCl₃) δ: 144.2, 125.6, 124.0, 83.3, 37.2, 24.6.

  2, 2'-(1, 4-Dioxaspiro[4.5]decane-8, 8-diyl)bis(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane) (2r):^[2a] White solid, 247.0 mg, 63% yield. m.p. 139~140 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 3.92 (s, 4H), 1.82 (t, J＝6.0 Hz, 4H), 1.61 (t, J＝6.2 Hz, 4H), 1.21 (s, 24H); ¹³C NMR (101 MHz, CDCl₃) δ: 109.2, 83.0, 64.0, 34.9, 26.8, 24.6.

  2, 2'-(9, 9-Dimethyl-1, 5-dioxaspiro[5.5]undecane-3, 3-diyl)bis(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane) (2s): White solid, 271.7 mg, 62% yield. m.p. 129~130 ℃; ¹H NMR (400 MHz, CDCl₃) δ: 3.47 (s, 4H), 1.74 (s, 6H), 1.22 (s, 26H), 0.94 (s, 6H); ¹³C NMR (101 MHz, CDCl₃) δ: 97.7, 82.9, 69.6, 32.3, 30.1, 25.2, 24.6, 22.6; HRMS (ESI) calcd for C₂₃H₄₃B₂O₆ [M+H]⁺ 437.3246, found 437.3251.

  2, 2'-(6-Methylhept-5-ene-2, 2-diyl)bis(4, 4, 5, 5-tetra-methyl-1, 3, 2-dioxaborolane) (2t): Colorless oil, 217.2 mg, 60% yield. ¹H NMR (400 MHz, CDCl₃) δ: 5.16 (t, J＝7.4Hz, 1H), 1.99~1.93 (m, 2H), 1.67 (s, 3H), 1.61 (s, 3H), 1.58~1.53 (m, 2H), 1.23 (s, 24H), 1.09 (s, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 130.5, 125.4, 82.7, 34.0, 26.1, 25.6, 24.6, 24.5, 17.4, 15.8; HRMS (ESI) calcd for C₂₀H₃₉B₂O₄ [M+H]⁺ 365.3034, found 365.3041.

  2, 2'-(Pentane-3, 3-diyl)bis(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane) (2u):^[13] Colorless oil, 68.3 mg, 42% yield. ¹H NMR (400 MHz, CDCl₃) δ: 1.66 (q, J＝7.6 Hz, 4H), 1.22 (s, 24H), 0.83 (t, J＝7.2 Hz, 6H); ¹³C NMR (101 MHz, CDCl₃) δ: 82.8, 24.7, 21.1, 11.2.

  2, 2'-(Pentane-2, 2-diyl)bis(4, 4, 5, 5-tetramethyl-1, 3, 2-dioxaborolane) (2v):^[13] Colorless oil, 85.0 mg, 52% yield. ¹H NMR (400 MHz, CDCl₃) δ: 1.53~1.49 (m, 2H), 1.35~1.17 (m, 26H), 1.05 (s, 3H), 0.88 (t, J＝7.2 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 82.8, 36.3, 24.6, 20.6, 15.9, 14.9.

  2, 2'-(Propane-2, 2-diyl-1, 1, 1, 3, 3, 3-d₆)bis(4, 4, 5, 5-tetra-methyl-1, 3, 2-dioxaborolane) (2w): Colorless oil, 71.1 mg, 47% yield. ¹H NMR (400 MHz, CDCl₃) δ: 1.21 (s, 24H); ¹³C NMR (101 MHz, CDCl₃) δ: 82.8, 24.6; HRMS (ESI) calcd for C₁₅H₂₄D₆B₂O₄Na [M+Na]⁺ 325.2605, found 325.2606.

  4.3   Scale-up Experiment

  In glove box, a 250 mL resealabel reaction tube of solvent flask equipped with a stirrer bar was charged with NaO^tBu (1.25 g, 13.0 mmol), B₂pin₂ (7.11 g, 28.0 mmol), FeBr₂ (215.7 mg, 1 mmol), and 50 mL of toluene. The tube was sealed with a Teflon screw cap and taken out of the glove box. The mixture was stirred at room temperature for 5 min. Subsequently, 3, 3-dimethyl-1, 5-dioxaspiro[5.5]- undecan-9-one (1.98 g, 10.0 mmol) was added under nitrogen atmosphere. Then, the tube was sealed and the mixture was heated at 100 ℃ with stirring for 5 h. Upon completion, ethyl acetate was added to the mixture to quench the reaction. The pure product 2s was obtained by flash column chromatography on silica gel.

  4.4   Procedure for the C—B functionalization of internal gem-diboroates

  4.4.1   Procedure for the synthesis of tertiary boronic ester 3a

  Compound 3a was prepared according literature.^[11] In glove box, a 25 mL resealable reaction tube of solvent flask equipped with a stirrer bar was charged with NaO^tBu (86.5 mg, 0.9 mmol), 2wa (115.4 mg, 0.39 mmol), and 3 mL of tetrahydrofuran (THF). The tube was sealed with a Teflon screw cap and taken out of the glove box. After that, 1-bromooctane (0.3 mmol, 57.9 mg) was added under N₂ atmosphere. Then the mixture was stirred at room temperature for 12 h. Upon completion, ethyl acetate was added to the mixture to quench the reaction. The pure product was obtained by flash column chromatography on silica gel. 4, 4, 5, 5-Tetra-methyl-2-(2-methyldecan-2-yl)- 1, 3, 2-dioxaborolane (3a): colorless oil, 70.3 mg, 83% yield. ¹H NMR (400 MHz, CDCl₃) δ: 1.26~1.22 (m, 26H), 0.91 (s, 6H), 0.88 (t, J＝6.4 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 82.8, 41.3, 31.9, 30.5, 29.6, 29.3, 26.5, 24.9, 24.7, 22.7, 14.1.

  4.4.2   Procedure for the synthesis of 1, 4-dione 3b

  Compound 3b was prepared according literature.^[1e] In glove box, a 25 mL resealable reaction tube of solvent flask equipped with a stirrer bar was charged with benzoic acid (30.5 mg, 0.25 mmol), 2wa (111.0 mg, 0.375 mmol), and 2 mL of THF. The tube was sealed with a Teflon screw cap and taken out of the glove box. Then the mixture was cooled to －30 ℃ and the MeLi (0.625 mmol, 1.6 mol/L in Et₂O) was added and stirred for 5 min. Then the cooling bath was removed and the reaction mixture was heated at 100 ℃ for 8 h. After that, the mixture was cooled to room temperature and Methyl bromoacetate (0.5 mmol, 76.5 mg) was added and stirred at 100 ℃ for 6 h. Upon completion, ethyl acetate was added to the mixture to quench the reaction. The pure product was obtained by flash column chromatography on silica gel. Methyl 3, 3-dimethyl-4-oxo-4-phenylbutanoate (3b): colorless oil, 43.3 mg, 78% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.62 (d, J＝8.0 Hz, 2H), 7.47~7.37 (m, 3H), 3.63 (s, 3H), 2.79 (s, 2H), 1.42 (s, 6H); ¹³C NMR (101 MHz, CDCl₃) δ: 208.6, 171.9, 139.1, 130.5, 128.0, 127.3, 51.5, 45.9, 45.0, 26.4; HRMS (ESI) calcd for C₁₃H₁₆O₃Na [M+Na]⁺ 243.0997, found 243.0994.

  4.4.3   Procedure for the synthesis of 4a

  Compound 4a was prepared according literature.^[15] At N₂ atmosphere, a 25 mL resealable reaction tube of solvent flask equipped with a stirrer bar was charged with 2-bromothiophene (58.7 mg, 0.36 mmol) and 2 mL of THF. The mixture was cooled to －78 ℃, then ⁿBuLi (0.36 mmol, 1.6 mol/L in hexane) was added. Removing the cooling bath and the mixture was stirred at room temperature for 1 h. After that, the mixture was cooled at －78 ℃ again, and 3a (0.3 mmol, 84.7 mg) was added as a solution in THF (1 mL) and stirred at this temperature for 1 h. Then the N-bromosuccinamide (NBS) (0.36 mmol, 64.1 mg) as a solution of THF (2 mL) was added and stirred for another 1 h. Saturated solution of Na₂S₂O₃ (2 mL) was added and the mixture was allowed to warm to room temperature. Upon completion, ethyl acetate was used to extract the aqueous layer. The pure product 4a was obtained by flash column chromatography on silica gel. 2-(2-Methyldecan-2-yl)thiophene (4a):^[15] colorless oil, 46.8 mg, 66% yield. ¹H NMR (400 MHz, CDCl₃) δ: 7.12~7.11 (m, 1H), 6.91~6.89 (m, 1H), 6.78~6.77 (m, 1H), 1.61~1.57 (m, 2H), 1.34 (s, 6H), 1.29~1.16 (m, 12H), 0.86 (t, J＝6.8 Hz, 3H); ¹³C NMR (101 MHz, CDCl₃) δ: 156.4, 126.2, 122.3, 121.9, 45.8, 37.5, 31.9, 30.2(2), 30.1(7), 29.5, 29.3, 24.7, 22.7, 14.1.

  Supporting Information  ¹H NMR and ¹³C NMR spectra of all prodoucts. The Supporting Information is available free of charge via the Internet at http://sioc-journal.cn.

  
  
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• 

  Scheme 1  Methods for the synthesis of internal gem-diboro- nates from ketones

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  Scheme 2  Gram scale synthesis of internal gem-diboronates

  Conditions and regents: 1s (10.0 mmol), B₂pin₂ (2.8 equiv. 28.0 mmol), NaO^tBu (1.3 equiv. 13.0 mmol), FeBr₂ (10 mol%, 1.0 mmol), toluene (50.0 mL), 100 ℃ for 5 h in N₂ atmosphere. Yields are based on isolated products

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  Scheme 3  Further application of internal gem-diboronates

  Reaction conditions: (a) 2wa (0.39 mmol), 1-bromoocatane (0.3 mmol), NaO^tBu (0.9 mmol), THF, r.t., 12 h; (b) 2wa (0.375 mmol), MeLi (0.625 mmol, 1.6 mol/L in diethyl ether), benzoic acid (0.25 mmol), methyl bromoacetate (0.5 mmol), THF; (c) 2-bromothiophene (0.36 mmol), ⁿBuLi (0.36 mmol, 1.6 mol/L in hexanes), 3a (0.3 mmol), NBS (0.36 mmol), THF.

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  Scheme 4  Proposed reaction mechanism

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  Table 1.  Reaction parameters of the deoxygenative gem- diborylation of ketones^a

  Entry	Variation from "standard conditions"	Yieldb/%
  1	None	73
  2	FeF2 instead of FeBr2	14
  3	FeCl2 instead of FeBr2	39
  4	Fe(OAc)2 instead of FeBr2	59
  5	No FeBr2	n.d.
  6	NaOtBu (0.4 equiv.)	Trace
  7	NaOtBu (2.0 equiv.)	59
  8	NaOtBu (3.0 equiv.)	32
  a Conditions: 1a (0.5 mmol), B2pin2 (2.8 equiv. 1.4 mmol), NaOtBu (1.3 equiv., 0.65 mmol), catalyst (10 mol%, 0.05 mmol), toluene (3.0 mL), 100 ℃, 5 h; b Determined by gas chromatography (GC) analysis using naphthalene as the internal standard.

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  Table 2.  Substrates scope of the iron catalyzed deoxygenative diborylation of ketones^a

  a Conditions: 1 (1.0 mmol), B2pin2 (2.8 equiv. 2.8 mmol), NaOtBu (1.3 equiv. 1.3 mmol), FeBr2 (10 mol%, 0.1 mmol), toluene (5.0 mL), 100 ℃ for 5 h in N2 atmosphere, yields are based on isolated products; b 0.5 mmol scale, toluene (3.0 mL); c B2pin2 (2.0 mmol), NaOtBu (1.5 mmol).

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•