Stereochemical Characterization of Polyketide Stereotriads

Sep 29, 2017 - School of Chemical Sciences, The University of Auckland, 23 Symonds Street, Auckland 1010, New Zealand. J. Org. Chem. , 2017, 82 (20), ...
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Cite This: J. Org. Chem. 2017, 82, 11225-11229

Stereochemical Characterization of Polyketide Stereotriads Synthesized via Hydrogen-Mediated Asymmetric syn-Crotylation Mathilde Pantin, Jonathan G. Hubert,† Tilo Söhnel, Margaret A. Brimble,* and Daniel P. Furkert* School of Chemical Sciences, The University of Auckland, 23 Symonds Street, Auckland 1010, New Zealand S Supporting Information *

ABSTRACT: The stereoselective access to stereotriads as important polyketide building blocks is reported on the basis of the Krische-type hydrogen-mediated syn-crotylation. The products were obtained with an extremely high diastereoselectivity (dr >99:1), and the newly formed syn stereocenters were controlled solely by the chiral catalyst. The stereochemistry was assigned by crystallography and HPLC for both product manifolds. This extension of the burgeoning transfer hydrogen methodology gives divergent asymmetric access to anti,syn and syn,syn polyketide stereotriads from the same α-chiral starting material and avoids potentially epimerizable aldehyde intermediates.

A

asymmetric anti-crotylation of alcohols using allylic acetates (10) as surrogates for crotylmetal reagents (Scheme 2)8 and syn-crotylation of alcohols using 2-phenyldimethylsilyl butadiene (13) have been developed.9 In the presence of an iridium or ruthenium catalyst and a chiral ligand based on SEGPHOS, the anti (11) or syn products (14) are obtained in high yields with excellent enantio- and diastereoselectivity, respectively. Although this chemistry and other new methods have been applied to the preparation of more complex extended polyketide arrays, including C2 symmetric stereopentads,10,11 to our knowledge, the stereochemical outcome of the application of these crotylation methods to the synthesis of polyketide stereotriads (e.g., 6−9)12 has not yet been systematically investigated.13a,b In the course of the synthetic studies toward natural products containing polyketide stereotriads, we were interested in examining the practical utility of syn-crotylation of α-chiral alcohols (15−17) in contrast to established methods requiring α-chiral aldehydes. At the outset of these studies, the stereochemical outcome in the presence of a pre-existing α-chiral center was uncertain; in earlier studies of direct alcohol crotylation using butadiene, the diastereoselectivity was found to be subject to unexpected controlling effects.14 Our investigations commenced with the application of the syn-crotylation conditions previously reported by Krische to the

symmetric crotylation is an important transformation for the assembly of polyketides and polyketide stereotriads in particular and has historically been the focus of many synthetic investigations.1 Seminal contributions from Brown2 and Roush3 (1 and 2, Scheme 1) and the work of many others4 have led to the development of reliable enantioselective methods that have been proven over decades of application in complex natural product synthesis and industrial settings. Despite this strong record of success, these classical methods demonstrate a number of practical drawbacks, including the requirement for preformed organometallic reagents, cryogenic temperatures, limitations from mismatched substrate/reagent combinations, and occasionally difficult work up and chromatographic purification. As a result, ongoing studies have continued toward methods using more convenient reagents and conditions and possessing improved process characteristics. From 2011, the Leighton group has reported a series of enantioselective crotylation reagents (3 and 4) based on a substituted 1,2diaminocyclohexyl auxiliary (Scheme 1).5,6 These crotylsilane reagents require operationally simple conditions and deliver crotylation products, including polyketide stereotriads 6−9, in excellent dr with generally high yields. In many cases the chiral auxiliary may be recovered during work up without chromatography, making these reagents advantageous for scale-up and process applications. Recently, the Krische group has pursued a new synthetic paradigm in hydrogen-mediated carbon−carbon bond formation, avoiding preformed organometallic reagents or carbonyl compounds.7 In particular, methods for the direct © 2017 American Chemical Society

Received: July 20, 2017 Published: September 29, 2017 11225

DOI: 10.1021/acs.joc.7b01820 J. Org. Chem. 2017, 82, 11225−11229

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The Journal of Organic Chemistry

Scheme 1. Established Crotylation Reagents (Left) and Application to Asymmetric Synthesis of Polyketide Stereotriads 6−9 (Right)5

Scheme 2. anti-Crotylation (Top) and syn-Crotylation (Bottom) of Alcohols Developed by Krische7,8

Table 1. Hydrogen-Mediated syn-Crotylation α-Chiral Alcohols 15−17a

entry 1 2 3 4 5 6 7 8 9

α-chiral PMB ether 15 derived from the Roche ester,15 and vinyl silane 13,16 with the chiral ligand (R)-DM-SEGPHOS, giving a single observable product diastereoisomer (18) in 35% yield (62% brsm) (Table 1, entry 1). Attempts to optimize this reaction by increasing the catalyst and/or ligand loading (Table 1, Entry 2), by adjusting the stoichiometry of vinyl silane 13 (Table 1, entries 3 and 4) or by removing the sodium sulfate additive (Table 1, entry 5), proved unsuccessful. Suspecting that the suboptimal result might be due the protecting group, the reaction was repeated using the corresponding TBS ether 16.17 A single product diastereoisomer (19) was again obtained in 22% yield (Table 1, entry 6), which increased to 80% yield upon removal of the sodium sulfate additive (Table 1, entry 7). The steric demand of the protecting group proved unimportant as TBDPS ether 1718 under identical conditions also afforded a single alcohol diastereomer 20a in 74% yield (82% brsm) (Table 1, entry 8). In order to examine the potential for matched/mismatched effects, the reaction was finally repeated employing (S)-DM-SEGPHOS (Table 1, entry 9), affording alcohol 20b as a single diastereoisomer in 64% yield (80% brsm).

alcohol 15 15 15 15 15 16 16 17 17

product 18 18 18 18 18 19 19 20a 20bi

yield (%)b

dr

c d

35 (63 ) 27e,f 26d,g 29d,h 23 22d 80 74 (82c) 64 (80c)

99.5:0.5 99.5:0.5 99.5:0.5

a Conditions: 13 (3 equiv), (R)-DM-SEGPHOS (5 mol %), RuHCl(CO)(PPh3)3 (5 mol %), toluene, 95 °C, 48 h, sealed tube. b Isolated yield after chromatography on neutral alumina. cBased on recovered starting material. dAnhydrous Na2SO4 (10 mol %) added. e Anhydrous Na2SO4 (20 mol %). f(R)-DM-SEGPHOS (10 mol %), RuHCl(CO)(PPh3)3 (10 mol %). g13 (1 equiv). h13 (6 equiv). i(S)DM-SEGPHOS (5 mol %).

To carefully establish the diastereoselectivity of the reaction, a racemic mixture of the racemic anti,syn and syn,syn isomers (20a−d) was prepared as an HPLC standard (Scheme 3). This reaction showed similar small diminution in yield for the all-syn compounds also suggested in Table 1 (entry 9). The anti,syn diastereoisomers (20a and 20c) were separable from syn,syn (20b and 20d) by chromatography. Comparison of the chiral HPLC traces obtained for single diastereoisomers 20a and 20b to the racemic standards established excellent dr values of 11226

DOI: 10.1021/acs.joc.7b01820 J. Org. Chem. 2017, 82, 11225−11229

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The Journal of Organic Chemistry Scheme 3. Syn-Crotylation of Racemic α-Chiral 17 with racDM-SEGPHOS19

In summary, the application of the hydrogen-mediated syncrotylation methodology developed by Krische to α-substituted alcohols is reported. Polyketide stereotriads possessing anti,syn and syn,syn relative stereochemistry were obtained in good yields, with nearly complete diastereoselectivity, as unambiguously confirmed by chiral HPLC and X-ray crystallography. Enantioselective synthesis of any of the four anti,syn and syn,syn stereotriads is therefore readily achievable by the appropriate choice of chiral pool starting material and chiral ligand. It might be expected that the investigation of the analogous anticrotylation would reveal a similar catalyst control, giving access to the remaining four possible diastereoisomers.11b The stereochemical determination presented here is expected to facilitate a further application of hydrogen-mediated crotylation methods to asymmetric polyketide synthesis, as a complement to other well-established preparative methods.

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EXPERIMENTAL SECTION

General. All reactions were performed under a nitrogen or argon atmosphere in oven-dried glassware. Toluene was purified on alumina oxide activated basic Brockmann grade 1, 58Å, then dried over 4Å molecular sieves. Chromatography was carried out using 0.063−0.1 mm silica gel (Davisil LC60A 40−63 Micron) or alumina oxide activated neutral Brockmann grade 1, 58 Å. Optical rotations were measured on a Rudolph Research Analytical-Autopol IV polarimeter. HRMS were recorded using a Bruker micrOTOF-QII mass spectrometer. NMR spectra were recorded at 21 °C in CDCl3 on a Bruker DRX400 spectrometer operating at 400 MHz for 1H nuclei and 100 MHz for 13C nuclei or on a Bruker Ascend 500 spectrometer operating at 500 MHz for 1H nuclei and 125 MHz for 13C nuclei. Chemical shifts were reported in parts per million (ppm) from tetramethylsilane (δ = 0 ppm) and measured relatively to the solvent in which the sample was analyzed (CDCl3 δ = 7.26 ppm for 1H NMR and δ = 77.16 ppm for 13C NMR). Coupling constants (J) were reported in hertz (Hz). 1H NMR data were reported as chemical shifts in ppm, followed by multiplicity (“s” singlet, “d” doublet, “dd” doublet of doublet, “ddd” doublet of doublet of doublet, “t” triplet, “m” multiplet, “b” broad), coupling constants where applicable, and relative integrals. 13C NMR spectra were reported as chemical shifts in ppm followed by the degree of hybridization. Compounds 15,15 16,17 and 1718 were prepared using literature methods. Vinyl Silane 13. Dimethylphenylsilane (3.2 mL, 20.9 mmol, 1.0 equiv), 1,4-dichloro-2-butyne (2.0 mL, 20.9 mmol, 1.0 equiv), and chloroplatinic acid hexahydrate (2.2 mg, 4.20 μmol, 0.02 mol %) were stirred at rt for 18 h. Chromatography (hexane/EtOAc, 49:1) afforded (E)-(1,4-dichlorobut-2-en-2-yl)dimethyl(phenyl)silane (3.48 g, 64%) as a colorless liquid: 1H NMR (CDCl3, 400 MHz) δ 7.57−7.52 (m, 2H), 7.41−7.37 (m, 3H), 6.15 (t, J = 7.2 Hz, 1H), 4.21 (d, J = 7.1 Hz, 2H), 4.13 (s, 2H), 0.48 (s, 6H); 13C NMR (CDCl3, 100 MHz) δ 141.6, 140.9, 136.4, 134.2(2), 129.7, 128.1(2), 39.7, 39.1, −2.9(2); HRMS (ESI) m/z calcd for C12H16Cl2NaSi [M + Na+] 281.0291, found 281.0298; IR νmax (neat) 2958, 1428, 1250, 700 cm−1. To a solution of (E)-(1,4-dichlorobut-2-en-2-yl)dimethyl(phenyl)silane (3.40 g, 13.1 mmol, 1.0 equiv) in EtOH (14 mL) at rt was added zinc dust (1.71 g, 26.2 mmol, 2.0 equiv). The reaction mixture was stirred at 85 °C for 4 h then filtered through a pad of Celite. The filtrate was washed with a saturated aqueous NaHCO3 solution (10 mL), and the organic layer was dried over anhydrous Na2SO4 and concentrated in vacuo to afford 13 (2.25 g, 91%) as a colorless liquid: 1 H NMR (CDCl3, 400 MHz) δ 7.55−7.51 (m, 2H), 7.37−7.33 (m, 3H), 6.48 (dd, J = 10.7, 17.7 Hz, 1H), 5.89 (d, J = 3.1 Hz, 1H), 5.52 (d, J = 3.0 Hz, 1H), 5.11 (d, J = 18.0 Hz, 1H), 5.02 (d, J = 10.5 Hz, 1H), 0.44 (s, 6H); 13C NMR (CDCl3, 100 MHz) δ 147.8, 141.3, 138.4, 134.1(2), 130.6, 129.2, 127.9(2), 116.8, −2.1(2). Data were in agreement with literature values.23 General Procedure for syn-Crotylation. A solution of protected alcohol (1.0 equiv) and vinyl silane 13 (3.0 equiv) in degassed toluene (2 M) was added to a Schlenk flask containing RuHCl(CO)(PPh3)3

99.5:0.5 for each compound.20 The absolute stereochemistry of both 20a and 20b was unambiguously determined by X-ray crystallography (see Supporting Information), following conversion to crystalline diols 21 and 22, respectively (Scheme 4). To further exemplify the synthetic utility of these vinyl Scheme 4. Synthesis of Crystalline Diols 21 and 22

silanes, 21 was readily converted to oxetane 23 in an essentially quantitative yield (Scheme 5). The vinyl silane functionality could then be transformed to either the corresponding vinyl bromide 24, by a bromination−debromosilylation sequence in 91% yield,8,21 or the use of cobalt-mediated conditions reported by Herzon22 afforded methyl ketone 25, again in a nearly quantitative yield. Scheme 5. Further Synthetic Elaboration of Diol 21

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DOI: 10.1021/acs.joc.7b01820 J. Org. Chem. 2017, 82, 11225−11229

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The Journal of Organic Chemistry

9.0 Hz, 1H), 3.06 (d, J = 6.9 Hz, 1H), 2.69−2.59 (m, 1H), 1.94 (bs, 1H), 1.69−1.59 (m, 1H), 0.98 (d, J = 7.0 Hz, 3H), 0.65 (d, J = 7.0 Hz, 3H), 0.42 (s, 3H), 0.41 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 153.9, 137.8, 134.0(2), 129.5, 128.1(2), 127.6, 77.3, 68.9, 39.8, 37.1, 13.4, 11.1, −2.4, −2.7; HRMS (ESI) m/z calcd for C16H26NaO2Si [M + Na]+ 301.1594, found 301.1588; IR νmax (neat) 3365, 2959, 1737, 1248 cm−1; [α]22 D −9.2 (c 0.42, CHCl3); mp 20−22 °C. (2S)-syn,syn Diol 22. Using the same procedure as for 21 above, deprotection of 20b (98 mg, 190 μmol) gave diol 22 (48 mg, 91%) as colorless crystals: 1H NMR (CDCl3, 400 MHz) δ 7.55−7.49 (m, 2H), 7.39−7.31 (m, 3H), 5.77 (dd, J = 0.9, 1.9 Hz, 1H), 5.54 (d, J = 2.4 Hz, 1H), 3.63 (dd, J = 2.9, 8.3 Hz, 1H), 3.52−3.44 (m, 2H), 2.52−2.40 (m, 1H), 1.96 (bs, 1H), 1.73−1.59 (m, 1H), 1.04 (d, J = 6.8 Hz, 3H), 0.76 (d, J = 7.1 Hz, 3H), 0.42 (s, 3H), 0.41 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 154.1, 138.2, 134.1(2), 129.3, 128.0(2), 127.3, 76.3, 67.8, 43.2, 36.5, 17.7, 9.8, −2.0, −2.2; HRMS (ESI) m/z calcd for C16H26NaO2Si [M + Na]+ 301.1594, found 301.1589; IR νmax (neat) 3365, 2959, 1737, 1248 cm−1; [α]25 D +19.8 (c 1.00, CHCl3); mp 80−82 °C. Oxetane 23. To a solution of diol 21 (57 mg, 0.21 mmol, 1.0 equiv) in CH2Cl2 (6 mL) at rt were added triethylamine (55 μL, 0.41 mmol, 2.0 equiv) and MsCl (16 μL, 0.21 mmol, 1.0 equiv). After stirring the solution at rt for 16 h, KOtBu (173 mg, 1.72 mmol, 4.0 equiv) was added. The reaction mixture was stirred for an additional 10 min, and then water was added. The organic layer was dried over anhydrous Na2SO4 and then concentrated in vacuo. Chromatography (petroleum ether/EtOAc, 95:5 to 9:1) afforded oxetane 23 (53 mg, 99%) as a yellow oil: 1H NMR (CDCl3, 400 MHz) δ 7.56−7.49 (m, 2H), 7.40−7.30 (m, 3H), 5.74−5.68 (m, 1H), 5.56−5.49 (m, 1H), 4.38 (dd, J = 5.7, 8.1 Hz, 1H), 4.26 (dd, J = 6.4, 8.8 Hz, 1H), 4.09 (dd, J = 5.8, 7.0 Hz, 1H), 2.63−2.52 (m, 1H), 2.40−2.28 (m, 1H), 1.05 (d, J = 6.8 Hz, 3H), 0.99 (d, J = 6.7 Hz, 3H), 0.42 (s, 3H), 0.41 (s, 3H); 13 C NMR (CDCl3, 100 MHz) δ 151.6, 137.9, 134.2(2), 129.2, 127.9(2), 127.1, 92.9, 74.5, 44.6, 34.6, 18.4, 17.5, −2.7, −2.9; HRMS (ESI) m/z calcd for C16H24NaOSi [M + Na]+ 283.1489, found 283.1481; IR νmax (neat) 2959, 1249, 1110 cm−1; [α]21 D −1.6 (c 0.50, CHCl3). Vinyl Bromide 24. To a solution of oxetane 23 (421 mg, 1.62 mmol, 1.0 equiv) in CH2Cl2 (4.7 mL) at 0 °C were added trimethylamine (262 μL, 1.94 mmol, 1.2 equiv) and pyridinium tribromide (620 mg, 1.94 mmol, 1.2 equiv), and the reaction was stirred at rt for 30 min. The above procedure was repeated three times until completion, monitored by TLC, and then the reaction mixture was quenched with a 4% aq sodium sulfite solution. The organic layer was dried over anhydrous Na2SO4 and then concentrated in vacuo. The crude product was dissolved in methanol (4.7 mL), and sodium methoxide (306 mg, 5.67 mmol, 3.5 equiv) was added. After 20 min of stirring the solution at rt, water was added, and the organic layer was dried over anhydrous Na 2 SO 4 and concentrated in vacuo. Chromatography (petroleum ether/Et2O, 95:5 to 9:1) afforded the vinyl bromide 24 (302 mg, 91%) as a colorless oil: 1H NMR (CDCl3, 400 MHz) δ 5.71 (d, J = 1.5 Hz, 1H), 5.49 (d, J = 1.5 Hz, 1H), 4.55 (dd, J = 5.9, 8.3 Hz, 1H), 4.29 (dd, J = 6.2, 8.5 Hz, 1H), 4.22 (dd, J = 5.9, 6.8 Hz, 1H), 2.81−2.63 (m, 2H), 1.22 (d, J = 6.8 Hz, 3H), 1.16 (d, J = 6.4 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 135.0 (C), 117.9 (CH2), 91.2 (CH), 74.9 (CH2), 50.8 (CH), 34.5 (CH), 18.2 (CH3), 15.4 (CH3); HRMS (ESI) m/z calcd for C8H13BrNaO [M + Na]+ 227.0043, found 227.0049; IR νmax (neat) 1739, 1217, 970, 758 cm−1; [α]23 D +18.6 (c 1.00, CHCl3). Ketone 25. A flask charged with oxetane 23 (200 mg, 0.75 mmol, 1.0 equiv), Co(acac)2 (193 mg, 0.75 mmol, 1.0 equiv), TBHP (94 μL, 0.75 mmol, 1.0 equiv), and triethylsilane (17 mg, 0.17 mmol, 0.1 equiv) in methanol (2 mL) was purged three times with oxygen. After stirring at room temperature for 16 h, the reaction mixture was purged with nitrogen and then concentrated in vacuo. Chromatography (petroleum ether/Et2O, 7:3) afforded ketone 25 (106 mg, 99%) as a colorless oil: 1H NMR (CDCl3, 400 MHz) δ 4.52 (dd, J = 8.2, 7.8 Hz, 1H), 4.46 (t, J = 6.8 Hz, 1H), 4.21 (dd, J = 6.7, 6.0 Hz, 1H), 2.97−2.88 (m, 1H), 2.84−2.72 (m, 1H), 2.19 (s, 3H), 1.22 (d, J = 6.8 Hz, 3H), 1.12 (d, J = 7.0 Hz, 3H); 13C NMR (CDCl3, 100 MHz) δ 210.7, 90.2,

(0.05 equiv) and (R)-(DM)-Segphos (0.05 equiv). The reaction mixture was stirred at 95 °C for 48 h then concentrated in vacuo. Chromatography on neutral alumina (hexane/EtOAc, 9:1) afforded the crotylation product and, in some cases, a small amount of the unreacted alcohol starting material. (2S)-anti,syn-PMB Vinyl Silane 18. Compound 18 was obtained as a colorless oil (396 mg, 35%) along with recovered alcohol 15 (22 mg, 8%): 1H NMR (CDCl3, 400 MHz) δ 7.54−7.46 (m, 2H), 7.37− 7.29 (m, 3H), 7.23−7.17 (m, 2H), 6.89−6.83 (m, 2H), 5.75 (d, J = 2.6 Hz, 1H), 5.51 (d, J = 2.5 Hz, 1H), 4.39 (d, J = 11.9 Hz, 1H), 4.34 (d, J = 11.6 Hz, 1H), 3.81 (s, 3H), 3.66−3.60 (m, 1H), 3.30 (dd, J = 4.5, 9.0 Hz, 1H), 3.26 (dd, J = 4.3, 9.0 Hz, 1H), 2.50−2.40 (m, 1H), 2.38 (d, J = 2.7 Hz, 1H), 1.81−1.71 (m, 1H), 1.03 (d, J = 6.8 Hz, 3H), 0.77 (d, J = 7.0 Hz, 3H), 0.39 (s, 6H); 13C NMR (CDCl3, 100 MHz) δ 159.3, 154.3, 138.4, 134.1(2), 130.5, 129.2(2), 127.9(3), 127.2, 113.9(2), 76.3, 75.3, 73.1, 55.4, 42.9, 35.1, 17.9, 10.6, −2.0, −2.1; HRMS (ESI) m/z calcd for C24H34NaO3Si [M + Na]+ 421.2169, found 421.2154; IR νmax (neat) 2962, 1719, 1249, 1109 cm−1; [α]21 D −2.2 (c 1.05, CHCl3). (2S)-anti,syn-TBS Vinyl Silane 19. Compound 19 was obtained as a colorless oil (86 mg, 80%): 1H NMR (CDCl3, 400 MHz) δ 7.54− 7.50 (m, 2H), 7.36−7.32 (m, 3H), 5.85 (dd, J = 1.4, 2.5 Hz, 1H), 5.61 (d, J = 1.2 Hz, 1H), 3.60 (dd, J = 4.3, 9.9 Hz, 1H), 3.44 (dd, J = 5.3, 9.8 Hz, 1H), 3.36−3.32 (m, 1H), 2.93 (d, J = 3.6 Hz, 1H), 2.54−2.48 (m, 1H), 1.69−1.59 (m, 1H), 1.02 (d, J = 7.0 Hz, 3H), 0.88 (s, 9H), 0.75 (d, J = 7.0 Hz, 3H), 0.41 (2 s, 6H), 0.03 (2 s, 6H); 13C NMR (CDCl3, 100 MHz) δ 154.1, 138.4, 134.1(2), 129.1, 127.9(2), 127.1, 76.2, 67.2, 41.0, 37.1, 26.0(3), 18.3, 14.1, 13.4, −2.1, −2.2, −5.4, −5.5; HRMS (ESI) m/z calcd for C22H40NaO2Si2 [M + Na]+ 415.2459, found 415.2443; IR νmax (neat) 2959, 1738, 1236, 1044 cm−1; [α]23 D −3.2 (c 1.00, CHCl3) (2S)-anti,syn-TBDPS Vinyl Silane 20a. Compound 20a was obtained as a colorless oil (174 mg, 74%) along with recovered alcohol 17 (15 mg, 10%): 1H NMR (CDCl3, 400 MHz) δ 7.68−7.64 (m, 4H), 7.51−7.35 (m, 8H), 7.32−7.27 (m, 3H), 5.83 (dd, J = 1.0, 2.3 Hz, 1H), 5.60 (d, J = 2.6 Hz, 1H), 3.69 (dd, J = 4.4, 10.1 Hz, 1H), 3.51 (dd, J = 4.5, 10.0 Hz, 1H), 3.46−3.39 (m, 1H), 2.70 (d, J = 3.5 Hz, 1H), 2.60−2.49 (m, 1H), 1.73−1.61 (m, 1H), 1.04 (s, 9H), 1.02 (d, J = 6.9 Hz, 3H), 0.79 (d, J = 7.0 Hz, 3H), 0.40 (s, 3H), 0.39 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 154.0, 138.3, 135.8(2), 134.1(2), 133.5, 133.4, 129.8(2), 129.1(3), 127.9(2), 127.8(4), 127.2, 75.3, 67.6, 40.8, 37.4, 27.0(3), 19.3, 14.1, 12.8, −2.1, −2.2; HRMS (ESI) m/z calcd for C32H44NaO2Si2 [M + Na]+ 539.2772, found 539.2762; IR νmax (neat) 2970, 1739, 1217, 1111 cm−1; [α]26 D −3.7 (c 1.05, CHCl3); HPLC Daicel Chiralpak AD-H column, n-hexane/iPrOH 99:1, 0.5 mL/min, 254 nm, tmajor = 8.0 min, tminor = 12.1 min, dr 99.5:0.5. (2S)-syn,syn-TBDPS Vinyl Silane 20b. Compound 20b was obtained as a colorless oil (100 mg, 64%) along with recovered alcohol 17 (15 mg, 20%): 1H NMR (CDCl3, 400 MHz) δ 7.69−7.60 (m, 4H), 7.53−7.35 (m, 8H), 7.32−7.27 (m, 3H), 5.74 (dd, J = 2.3, 2.4 Hz, 1H), 5.49 (d, J = 2.9 Hz, 1H), 3.76−3.68 (m, 1H), 3.49 (dd, J = 4.6, 9.9 Hz, 1H), 3.46 (dd, J = 4.2, 10.1 Hz, 1H), 2.56 (d, J = 2.4 Hz, 1H), 2.49−2.39 (m, 1H), 1.73−1.62 (m, 1H), 1.06 (d, J = 6.8 Hz, 3H), 1.05 (s, 9H), 0.73 (d, J = 7.3 Hz, 3H), 0.40 (s, 3H), 0.39 (s, 3H); 13C NMR (CDCl3, 100 MHz) δ 154.2, 138.3, 135.9(2), 135.7(2), 134.1(2), 133.4, 133.2, 129.9(2), 129.2, 127.9(2), 127.9(4), 127.2, 76.7, 69.4, 43.1, 36.6, 27.1(3), 13.9, 19.3, 18.5, −2.0, −2.2; HRMS (ESI) m/z calcd for C32H44NaO2Si2 [M + Na]+ 539.2772, found 539.2772; IR νmax (neat) 2970, 1739, 1217, 1111 cm−1; [α]28 D −5.8 (c 0.80, CHCl3); HPLC Daicel Chiralpak AD-H column, n-hexane/iPrOH 99:1, 0.5 mL/min, 254 nm, tmajor = 11.1 min, tminor = 12.4 min, dr 99.5:0.5. (2S)-anti,syn Diol 21. To a solution of vinyl silane 20a (40 mg, 77 μmol, 1.0 equiv) in THF (0.5 mL) at rt was added TBAF (1 M in THF, 77 μL, 77 μmol, 1.0 equiv). After stirring at rt for 20 min, the reaction mixture was quenched with a saturated aq NH4Cl solution and diluted with Et2O. The organic layer was dried over anhydrous Na2SO4 then concentrated in vacuo. Chromatography (petroleum ether/EtOAc, 9:1 to 2:1) afforded 20a (21 mg, 98%) as colorless crystals: 1H NMR (CDCl3, 400 MHz) δ 7.51−7.46 (m, 2H), 7.38− 7.34 (m, 3H), 5.84 (dd, J = 1.9, 1.6 Hz, 1H), 5.71 (d, J = 2.3 Hz, 1H), 3.57−3.48 (m, 1H), 3.43 (dd, J = 7.8, 10.8 Hz, 1H), 3.17 (dd, J = 2.4, 11228

DOI: 10.1021/acs.joc.7b01820 J. Org. Chem. 2017, 82, 11225−11229

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The Journal of Organic Chemistry 75.4, 52.7, 34.0, 30.2, 18.3, 11.8; HRMS (ESI) m/z calcd for C8H14NaO2 [M + Na]+ 165.1886, found 165.1883; Rf 0.34 (petroleum ether/Et2O, 7:3); IR νmax (neat) 2933, 2161, 1710, 1455 cm−1; [α]21 D −29.5 (c 1.60, CHCl3).

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(9) Zbieg, J. R.; Moran, J.; Krische, M. J. J. Am. Chem. Soc. 2011, 133, 10582−10586. (10) Gao, X.; Han, H.; Krische, M. J. Am. Chem. Soc. 2011, 133, 12795−12800. (11) (a) Kotani, S.; Kai, K.; Sugiura, M.; Nakajima, M. Org. Lett. 2017, 19, 3672−3675. (b) Chemler, S. R.; Roush, W. R. J. Org. Chem. 1998, 63, 3800−3801. (12) (a) Rauniyar, V.; Hall, D. G. Angew. Chem., Int. Ed. 2006, 45, 2426−2428. (b) Chen, M.; Roush, W. R. J. Am. Chem. Soc. 2012, 134, 3925−3931. (13) (a) An example of an anti,anti stereotriad synthesis via the Krische anti-crotylation has been reported, but the authors made no comment on the reaction stereochemistry: Oshita, J.; Noguchi, Y.; Watanabe, A.; Sennari, G.; Sato, S.; Hirose, T.; Oikawa, D.; Inahashi, Y.; Iwatsuki, M.; Ishiyama, A.; Omura, S. Tetrahedron Lett. 2016, 57, 357−360. (b) The compound in question had previously been prepared by the Roush group in their total synthesis of bafilomycin A1: Scheidt, K. A.; Bannister, T. D.; Tasaka, A.; Wendt, M. D.; Savall, B. M.; Fegley, G. J.; Roush, W. R. J. Am. Chem. Soc. 2002, 124, 6981− 6990. (14) McInturff, E. L.; Yamaguchi, E.; Krische, M. J. J. Am. Chem. Soc. 2012, 134, 20628−20631. (15) Lentsch, C.; Furst, R.; Mulzer, J.; Rinner, U. Eur. J. Org. Chem. 2014, 2014, 919−923. (16) For the preparation by adaption of a reported method, see the Experimental Section for details. Franck-Neumann, M.; Sedrati, M.; Mokhi, M. J. Organomet. Chem. 1987, 326, 389−404. (17) Han, J.-C.; Liu, L.-J.; Chang, Y.-Y.; Yue, G.-Z.; Guo, J.; Zhou, L.Y.; Li, C.-C.; Yang, Z. J. Org. Chem. 2013, 78, 5492−5504. (18) Pasqua, A. E.; Ferrari, F. D.; Hamman, C.; Liu, Y.; Crawford, J. J.; Marquez, R. J. Org. Chem. 2012, 77, 6989−6997. (19) An equimolar mixture of (R)-DM-SEGPHOS and (S)-DMSEGPHOS was used. (20) See the Supporting Information for HPLC data. (21) Miller, R. B.; McGarvey, G. J. Org. Chem. 1979, 44, 4623−4633. (22) Ma, X.; Herzon, S. B. J. Org. Chem. 2016, 81, 8673−8695. (23) Pidaparthi, R.; Junker, C. S.; Welker, M. E.; Day, C. S.; Wright, M. W. J. Org. Chem. 2009, 74, 8290−8297.

ASSOCIATED CONTENT

S Supporting Information *

The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc.7b01820. Copies of spectra for all compounds, chiral HPLC traces, and ORTEP diagrams for 21 and 22 (PDF) Crystal data for 21 (CIF) Crystal data for 22 (CIF)

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AUTHOR INFORMATION

Corresponding Authors

*E-mail: [email protected]. *E-mail: [email protected]. ORCID

Margaret A. Brimble: 0000-0002-7086-4096 Daniel P. Furkert: 0000-0001-6286-9105 Present Address †

ETH Zürich, Rämistrasse 101, 8092 Zürich, Suisse.

Notes

The authors declare no competing financial interest.

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ACKNOWLEDGMENTS The authors thank Dr. Tilo Söhnel and Tatiana Groutso (UoA) for assistance with X-ray crystallography and The University of Auckland for the award of a UoA doctoral scholarship to J.G.H.

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REFERENCES

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DOI: 10.1021/acs.joc.7b01820 J. Org. Chem. 2017, 82, 11225−11229