An expedient total synthesis of mupirocin H

Abstract

An efficient stereoselective total synthesis of (+)-mupirocin H is described. The chiron and asymmetric strategies were appropriately utilized for the rapid construction of the novel five-membered lactone with six stereogenic centres. The C3–C5 triol segment was derived directly from readily-available D-ribose, and the chirality at the C6 position was introduced by means of substrate-controlled conjugate addition. The remaining chiral centers (C10 and C11) were obtained by Oppolzer's protocol, and the olefin was generated through a Julia–Kocienski olefination.

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Introduction

Mupirocin is a mixture of pseudomonic acids containing 95% of pseudomonic acid A along with pseudomonic acids B–D (Fig. 1). Mupirocin is a polyketide antibiotic used in the treatment of skin infections and is a strong inhibitor of Gram-positive bacteria and mycoplasmal pathogens, including methicillin-resistant S. aureus (MRSA).¹ Mupirocin W² (1) and H³ (2), which are often confused with mupirocin, are the pseudomonic acid analogues isolated from Pseudomonas fluorescens. While mupirocin W has been found to display reduced activity compared to P. Fluorescens against Bacillus subtilis,² the biological activity of mupirocin H, the first truncated analogue of pseudomonic acid, has yet to be investigated. The pseudomonic acid class of molecules all bear a similar C1–C14 carbon framework (Fig. 1) with a central tetrahydropyran ring, whereas mupirocin H and W lack the characteristic tetrahydropyran nucleus and instead contain a 5-membered tetrahydrofuranone/tetrahydrofuran moiety.

Fig. 1 Structures of pseudomonic acids and mupirocins H & W.

The unusual structures of the pseudomonic acid class of compounds along with their striking biological properties have provoked many attempts to target them for individual synthesis.⁴ Chakraborty et al.^5a accomplished the first total synthesis of mupirocin H in 19 steps using D-glucose as the chiral source and Julia–Kociensky olefination as the key step. Later, Willis et al.^5b demonstrated a convergent synthesis of mupirocin H while developing a strategy for the synthesis of functionalized γ-lactones. While our work was in progress, She et al.^5c disclosed a scalable approach involving seven steps (longest linear sequence) for the synthesis of mupirocin H employing Suzuki–Miyaura coupling and Mukaiyama aldol reaction as the key steps. In continuation of our work on the total synthesis of natural products,⁶ we have recently accomplished the total synthesis of pseudomonic acid methyl monate C.⁷ Herein, we describe an efficient strategy for the total synthesis of mupirocin H following a chiron approach.

Results and discussion

Retrosynthetically, it was envisioned that the target compound mupirocin H could be synthesized from the advanced precursor 3 by the selective oxidation of the terminal olefin followed by functional group interconversion (Scheme 1). The intermediate 3 was planned to be obtained by the coupling of two counterparts, aldehyde 4 and sulfone 5, via a Julia–Kocienski olefination reaction. The aldehyde 4 can be synthesized from α,β-unsaturated ester 6 (in a three-step sequence), and 6 be easily prepared from D-(−)-ribose following established synthetic techniques. Sulfone 5 can be accessed from propionate 7 by following Oppolzer's aldol protocol.

Scheme 1 Retrosynthetic analysis of mupirocin H.

With the devised synthetic strategy, we achieved the rapid construction of the Michael acceptor 6 from the known diol 8 (ref. 8) (Scheme 2) obtained from D-(−)-ribose in two steps. The twofold silylation of 8 with tert-butyldimethylsilyl chloride (TBSCl) in the presence of imidazole provided 9, which on mono-desilylation with HF-pyridine afforded the known alcohol 10.⁹ The Swern oxidation¹⁰ of the alcohol 10 followed by Horner Wittig Emmons olefination under the defined conditions for α-oxygenated aldehydes¹¹ gave the ester 6.

Scheme 2 Reagents and conditions: (a) TBSCl, Im, CH₂Cl₂, rt, 12 h, 95%; (b) 70% HF in pyridine, THF, 0 °C – rt, 12 h, 90%; (c) (i) (COCl)₂, DMSO, Et₃N, CH₂Cl₂, 2 h, (ii) triethyl phosphano acetate, n-BuLi, DME then aldehyde, 0 °C, 5 min, overall 85%; (d) Me₂LiCu, TMSCl, THF, −78–0 °C, 5 min, 95%, dr = 13 : 1 (12 : 12a); (e) LiAlH₄, THF, 0 °C, 5 min. 95% (12 (88%), 12a (7%)); (f) Dess–Martin periodinane, CH₂Cl₂, rt, 90%.

The key C6 methyl substituent was installed by taking advantage of the neighbouring chirality in γ-alkoxy-α,β-enoate 6 (Scheme 2), where in the methyl nucleophile was introduced onto the Michael acceptor 6 by the substrate-controlled conjugate addition¹² of dimethyl lithium cuprate in the presence of the electrophilic additive TMSCl in a stereo-controlled manner to provide the unseparable diastereomeric mixture of 11 (dr ratio 13 : 1). The stereoselectivity in this process can be explained by Kornieko's reductive elimination analogy¹³ and by following the possible transition states (Fig. 2). The diastereomers formed in this stage were separated after reduction of the ester functionality with LiAlH₄ to yield the corresponding alcohols 12 and 12a. Based on the theoretical predictions, we proceeded further with the major isomer 12 towards oxidation under Dess–Martin conditions¹⁴ to afford the desired aldehyde 4. The stereochemistry of 12 at the C6 carbon was later validated by its utility in synthesizing the target mupirocin H 2 (vide infra).

Fig. 2 Proposed reductive elimination model-based transition states for the diastereoselective conjugate addition process.

For the synthesis of the sulfone 5, we started with the aldol addition of Oppolzer's propionate 7 on acetaldehyde.¹⁵ When the silyl ketene-N,O-acetal of 7 (generated in situ by the treatment of 7 with Et₃N and TBSOTf) was added to a solution of acetaldehyde and TiCl₄ in CH₂Cl₂ at −78 °C, the reaction proceeded smoothly to afford the enantiopure aldol adduct 13. Protection of the secondary alcohol as the corresponding silyl ether 14 (TBS ether) followed by cleavage of sultam with LiAlH₄ provided the alcohol 15. Alcohol 15 was transformed to a sulfide with phenyl tetrazole thiol under Mitsunobu conditions¹⁶ and further oxidized to sulfone 5 using an ammonium molybdate–H₂O₂ combination without affecting the TBS functionality (Scheme 3).

Scheme 3 Reagents and conditions: (a) (i) Et₃N, TBSOTf, CH₂Cl₂, rt, 24 h, (ii) acetaldehyde, TiCl₄, CH₂Cl₂, −78 °C, 5 min, 59%, 98% (brsm); (b) lutidine, TBSOTf, CH₂Cl₂, 0 °C, 5 min, 90%; (c) LiAlH₄, THF, 0 °C, 5 min, 90%; (d) (i) PPh₃, DIAD, 1-phenyl-1H-tetrazole-5-thiol, THF, 0 °C, 30 min, (ii) (NH₄)₆Mo₇O₂₄·4H₂O, H₂O₂, EtOH, rt, 6 h, 85% overall.

Coupling of the two fragments aldehyde 4 and sulfone 5 by Julia–Kocienski olefination¹⁷ proceeded smoothly under previously optimized conditions⁷ to provide diene 3 in 80% yield. The selective oxidation of the terminal olefin of diene 3 was again a challenge. In order to get the desired transformation, we first utilized an acetonide-directed regioselective Wacker oxidation¹⁸ reaction that quantitatively transformed allylic diol acetonides and carbonates to aldehydes rather than methyl ketones. Our attempts were not successful, however, as the substrate 3 remained inert under the respective conditions. Alternatively, we proceeded with the selective hydroboration of the terminal olefin by boranes. After screening several reagents for this transformation,¹⁹ treatment of diene 3 with Cy₂BH (ref. 20) followed by oxidation with H₂O₂ resulted in the successful formation of alcohol 16. Alcohol 16 was further oxidized with a TEMPO–BAIB (ref. 21) combination to deliver the acid precursor 17. We needed to remove the protecting groups and lactonize the acid functionality with C4 alcohol to achieve the target. Towards this, we chose a one-pot cascade process wherein acid 17 was treated with 6 M HCl to facilitate di-TBS deprotection, acetonide deprotection and simultaneous lactonization to give mupirocin H 2 (Scheme 4). The ¹H and ¹³C NMR spectra of this synthetic compound were identical with those of the natural compound³ as well as the previously synthesized mupirocin H.⁵

Scheme 4 Reagents and conditions: (a) KHMDS, then aldehyde 4, −78 °C – rt, 3 h, 80%; (b) Cy₂BH, THF, then H₂O₂, NaOH, 3 h, 70%; (c) TEMPO, BAIB, MeCN–H₂O (1 : 1), rt, 88%; (d) 6 M HCl, THF, 80 °C, 1 h, 85%.

Conclusions

In conclusion, we have established a modular and straightforward approach for the synthesis of mupirocin H with an overall yield of 26.8% for the longest linear sequence in eight steps from the known intermediate 10. Further investigation on this synthetic strategy for the synthesis of mupirocin W 1 is currently underway in our laboratory.

Experimental section

General methods

¹H NMR and ¹³C NMR spectra were recorded in CDCl₃ on a 300- or 500 MHz spectrometer at ambient temperature. The coupling constant J is given in Hz. The chemical shifts are reported as ppm downfield from the TMS internal standard, and signal patterns are indicated as follows: s = singlet, d = doublet, t = triplet, q = quartet, sext = sextet, m = multiplet and br = broad. FTIR spectra were recorded on KBr pellets and are reported in wave number (cm⁻¹). Optical rotations were measured on a digital polarimeter using a 1 mL cell with a path length of 1 dm. For low (MS) and high (HRMS) resolution, m/z ratios are reported as values in atomic mass units. Mass analysis was done in ESI mode. All reagents were reagent grade and used without further purification unless specified otherwise. Solvents for reactions were distilled prior to use; THF and diethyl ether were distilled from Na and benzophenone ketyl, and CH₂Cl₂ was distilled from CaH₂. All air- or moisture-sensitive reactions were conducted under a nitrogen or argon atmosphere in flame- or oven-dried glassware with magnetic stirring. Column chromatography was carried out using silica gel (100–200 mesh) packed in glass columns. Technical grade ethyl acetate and petroleum ether used for column chromatography were distilled prior to use.

(R)-5-((4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-2,2,3,3,8,8,9,9-octamethyl-4,7-dioxa-3,8-disiladecane (9)

To a magnetically stirring solution of 8 (2.0 g, 10.6 mmol) in CH₂Cl₂ (20 mL), imidazole (4.34 g, 63.84 mmol), TBSCl (4.8 g, 31.92 mmol), and DMAP (0.64 g, 5.2 mmol) were added at 0 °C under nitrogen atmosphere, and stirring was continued until the starting material was completely consumed (ca. 12 h). The reaction mixture was quenched with sat. aq. NH₄Cl (10 mL), diluted with water (10 mL), and extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layer was washed with brine (10 mL) and dried over anhydrous Na₂SO₄. Evaporation of CH₂Cl₂ in vacuo gave the crude product, which was subjected to silica gel column chromatography to give the desired product 9 as a colorless liquid (4.2 g, 95%); R_f = 0.5 (hexane–EtOAc, 19 : 1); [α]²⁴_D = −22.8 (c 0.35, CHCl₃); IR (KBr): 2955, 2890, 1642, 1467, 1254, 1093, 835 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 5.9 (ddd, J = 17.4, 10.4, 7.2 Hz, 1H), 5.33 (d, J = 17.0 Hz, 1H), 5.21 (d, J = 10.4 Hz, 1H), 4.60–4.56 (m, 1H), 4.25–4.21 (m, 1H), 3.81–3.77 (m, 1H), 3.74 (dd, J = 10.8, 3.4 Hz, 1H), 3.67 (dd, J = 10.8, 4.4 Hz, 1H), 1.46 (s, 3H), 1.35 (s, 3H), 0.90 (s, 9H), 0.88 (s, 9H), 0.09 (s, 3H), 0.06 (s, 3H), 0.05 (s, 6H) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 135.1, 117.5, 108.1, 78.8, 77.6, 72.6, 64.8, 27.8, 25.9, 25.4, 18.4, 18.2, −3.8, −4.6, −5.4, −5.5 ppm; MS m/z 439 [M + Na]⁺; HRMS calcd for C₂₁H₄₄O₄NaSi₂ [M + Na]⁺ 439.2670, found 439.2672.

(R)-2-((tert-Butyldimethylsilyl)oxy)-2-((4S,5S)-2,2-dimethyl-5-vinyl-1,3-dioxolan-4-yl)ethanol (10)

To the magnetically stirring solution of 9 (7 g, 16.8 mmol) in THF (90 mL) in a Teflon vial, HF–pyridine (7 : 3 complex, 4.4 mL) was added at 0 °C, and stirring was continued at the same temperature while the reaction progress was monitored by TLC analysis. After complete consumption of starting material (ca. 12 h), the reaction mixture was neutralized with solid NaHCO₃ and filtered. The filtrate was concentrated to give the crude mass, which, upon column purification (EtOAc–hexane 1 : 9), gave the mono TBS ether 10 as a colorless oil (4.6 g, 90%); R_f = 0.5 (hexane–EtOAc, 8 : 2); [α]²⁴_D = −32.8 (c 0.4, CHCl₃); IR (KBr): 3339, 2932, 2896, 1466, 1373, 1252, 1079, 836 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 5.93 (ddd, J = 17.4, 10.3, 7.3 Hz, 1H), 4.91 (d, J = 17.1 Hz, 1H), 5.26 (ddd, J = 10.3, 1.6, 0.9 Hz, 1H), 4.66–4.59 (m, 1H), 4.19 (dd, J = 7.6, 6.2 Hz, 1H), 3.85–3.78 (m, 1H), 3.76–3.68 (m, 2H), 1.48 (s, 3H), 1.38 (s, 3H), 0.88 (s, 9H), 0.10 (s, 3H), 0.07 (s, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 134.1, 118.4, 108.5, 79.5, 78.8, 70.8, 65.0, 27.8, 25.9, 25.4, 18.0, −3.7, −4.4 ppm; MS m/z 325 [M + Na]⁺; HRMS calcd for C₁₅H₃₀O₄NaSi [M + Na]⁺ 325.1805, found 325.1803.

(R,E)-Ethyl-4-((tert-butyldimethylsilyl)oxy)-4-((4S,5S)-2,2-dimethyl-5-vinyl-1,3-dioxolan-4-yl)but-2-enoate (6)

Freshly distilled DMSO (3.02 mL, 42.4 mmol) was added dropwise to a cooled (−78 °C) solution of oxalyl chloride (1.83 mL, 21.2 mmol) in anhydrous CH₂Cl₂ (60 mL). Five minutes later, a solution of alcohol 10 (3.2 g, 10.6 mmoL) in CH₂Cl₂ (30 mL) was added, and the mixture was stirred at −78 °C for 30 minutes. Subsequently, Et₃N (8.9 mL, 63.6 mmol) was added, and stirring continued for 15 minutes at the same temperature and for 30 minutes while slowly warming to room temperature. The reaction was then quenched with 40 mL of phosphate buffer solution and extracted with CH₂Cl₂ (3 × 20 mL). The combined extracts were washed with water (20 mL) and brine (20 mL), dried over Na₂SO₄ and concentrated under reduced pressure. The resulting 3.2 g (42.3 mmol, 100%) of pure aldehyde was dissolved in anhydrous DME (20 mL) and added to a mixture of triethyl phosphonoacetate (3.7 g, 15.9 mmol) and n-BuLi (1.6 M in hexane, 9.94 mL) in anhydrous DME (10 mL) that had been pre-stirred for 20 minutes before the addition. Within five minutes, all the starting material was consumed (the reaction was monitored by TLC), and the reaction was quenched with sat. aq. NaHCO₃ (10 mL) at 0 °C and extracted with CH₂Cl₂ (3 × 20 mL). The combined extracts were washed with brine (30 mL), dried over Na₂SO₄ and concentrated to give the crude product, which, upon silica gel column purification (EtOAc–hexane, 1 : 19), gave ester 6 (3.31 g, 85% for two steps) as a pale yellow oil; R_f = 0.5 (hexane–EtOAc, 9 : 1); [α]²⁴_D = +8.0 (c 0.25, CHCl₃); IR (KBr): 2935, 2860, 1734, 1466, 1374, 1259, 1077, 840 cm⁻¹; ¹H NMR (300 MHz, CDCl₃): δ 6.89 (dd, J = 15.7, 6.3 Hz, 1H), 5.97 (dd, J = 15.9, 1.3 Hz, 1H), 6.04–5.93 (m, 1H), 5.38 (d, J = 17.1 Hz, 1H), 5.25 (d, J = 10.3 Hz, 1H), 4.68–4.61 (m, 1H), 4.37–4.30 (m, 1H), 4.20 (q, J = 7.1 Hz, 2H), 4.12–4.06 (m, 1H), 1.46 (s, 3H), 1.34 (s, 3H), 1.29 (t, J = 7.1 Hz, 3H), 0.89 (s, 9H), 0.05 (s, 3H) 0.02 (s, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 166.1, 147.5, 133.8, 122.6, 118.2, 108.7, 80.6, 78.6, 71.2, 60.4, 27.4, 25.8, 25.2, 18.1, 14.2,−3.7, −4.7 ppm; MS m/z 393 [M + Na]⁺; HRMS calcd for C₁₉H₃₄O₅NaSi [M + Na]⁺ 393.2067, found 393.2067.

(3R,4R)-Ethyl-4-((tert-butyldimethylsilyl)oxy)-4-((4S,5S)-2,2-dimethyl-5-vinyl-1,3-dioxolan-4-yl)-3-methylbutanoate (11)

MeLi (1.6 M in hexane, 60.8 mL, 97.3 mmol) was added to a stirring suspension of CuI (9.3 g, 48.65 mmol) in THF (50 mL) at −20 °C. The resulting solution was stirred at this temperature for 20 minutes and then cooled to −78 °C. To this solution, TMSCl (18.6 mL, 145.95 mmol) was added dropwise followed by canulation with a solution of α,β-unsaturated ester 6 (3.0 g, 8.11 mmol) in THF (30 mL) at −78 °C. Within five minutes, all starting material was consumed (reaction monitored by TLC), and the reaction was quenched with NH₄OH–NH₄Cl (1 : 1) solution (100 mL) at −78 °C and allowed to warm to room temperature. The reaction mixture was extracted with EtOAc (3 × 20 mL). The combined extracts were washed with NH₄OH–NH₄Cl (1 : 1) solution (100 mL) and brine (20 mL) solution, dried over anhydrous Na₂SO₄ and concentrated. The concentrated residue was purified by silica gel column chromatography (EtOAc–hexane 1 : 19) to afford a diastereomeric mixture of 11 (2.96 g, 95%; 13 : 1 ratio as observed in ¹H NMR) as a colorless oil; R_f = 0.55 (hexane–EtOAc, 9 : 1); IR (KBr): 2957, 2900, 1736, 1466, 1375, 1253, 1084, 839 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 5.90 (ddd, J = 17.9, 10.2, 7.6 Hz, 1H), 5.31 (ddd, J = 17.2, 1.7, 1.1 Hz, 1H), 5.23 (d, J = 10.2 Hz, 1H), 4.55–4.50 (m, 1H), 4.18–4.07 (m, 3H), 3.76 (dd, J = 7.9, 2.7 Hz 1H), 2.61 (dd, J = 15.3, 5.2 Hz, 1H), 2.34–2.26 (m, 1H), 2.25 (dd, J = 15.3, 8.7 Hz, 1H), 1.45 (s, 3H), 1.34 (s, 3H), 1.25 (t, J = 7.2 Hz, 3H), 1.02 (d, J = 6.7 Hz, 3H), 0.87 (s, 9H), 0.09 (s, 3H), 0.04 (s, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 173.6, 134.9, 118.4, 108.3, 79.4, 78.8, 72.6, 60.1, 37.7, 35.2, 28.0, 26.0, 25.5, 18.2, 14.4, 14.3, −3.7, −4.3 ppm; MS m/z 409 [M + Na]⁺; HRMS calcd for C₂₀H₃₈O₅NaSi [M + Na]⁺ 403.2380, found 409.2380.

(3R,4R)-4-((tert-Butyldimethylsilyl)oxy)-4-((4S,5S)-2,2-dimethyl-5-vinyl-1,3-dioxolan-4-yl)-3-methylbutan-1-ol (12)

Ester 11 (3.00 g, 7.76 mmol) was added to a magnetically stirring suspension of LiAlH₄ (0.3 g, 7.76 mmol) in THF (20 mL) at 0 °C. Within five minutes, all the starting material was consumed, and the reaction mixture was then quenched with sat. aq. Na₂SO₄ (5 mL). Silica gel (5.00 g) was added, and the resulting white suspension was stirred at rt for 30 minutes and filtered. The filtrate was dried over anhydrous Na₂SO₄ and concentrated under reduced pressure to give the crude product. Upon column purification through a short pad of silica gel (hexane–EtOAc 4 : 1), alcohol 12 (2.34 g, 88%) was obtained as a colorless oil along with 12a as colorless oil (0.186 g, 7%); R_f = 0.50 (hexane–EtOAc 3 : 2); [α]²⁴_D = −48.3 (c 0.25, CHCl₃); IR (KBr): 3344, 2935, 2860, 1469, 1374, 1253, 1083, 840 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 5.99–5.87 (m, 1H), 5.36–5.30 (m, 1H), 5.28–5.24 (m, 1H), 4.56–4.51 (m, 1H), 4.14 (dd, J = 7.9, 5.5 Hz, 1H), 3.82 (dd, J = 7.9, 2.5 Hz, 1H), 3.77–3.69 (m, 1H), 3.65–3.59 (m, 1H), 2.01–1.90 (m, 1H), 1.85–1.66 (m, 2H), 1.61–1.52 (m, 1H), 1.45 (s, 3H), 1.35 (s, 3H),1.01 (d, J = 7.0 Hz, 3H), 0.87 (s, 9H), 0.07 (s, 3H) 0.04 (s, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 134.8, 118.5, 108.1, 79.3, 78.9, 73.3, 61.3, 35.1, 34.8, 28.2, 26.0, 25.5, 18.2, 15.3, −3.7, −4.2 ppm; MS m/z 367 [M + Na]⁺; HRMS calcd for C₁₈H₃₆O₄NaSi [M + Na]⁺ 367.2275, found 367.2279.

(3R,4R)-4-(tert-Butyldimethylsilyloxy)-4-((4S,5S)-2,2-dimethyl-5-vinyl-1,3-dioxolan-4-yl)-3-methylbutanal (4)

To a magnetically stirring solution of alcohol 12 (1.5 g, 4.35 mmol) in CH₂Cl₂ (20 mL), Dess–Martin periodinane (2.19 g, 5.22 mmol) was added at 0 °C. Stirring was continued until the starting material was completely consumed (ca. 2 h). The reaction mixture was filtered through a small pad of celite, and the filtrate was washed with sat. aq. NaHCO₃ (20 mL), dried over anhydrous Na₂SO₄, filtered, and concentrated under reduced pressure to give the crude product. Upon column purification (hexane–EtOAc, 9 : 1), the aldehyde 4 (1.35 g, 90%) was obtained as a colorless oil. The aldehyde was immediately utilized for the next Julia–Kocienski olefination reaction. R_f = 0.50 (hexane–EtOAc, 4 : 1); [α]²⁴_D = −33.5 (c 0.38, CHCl₃); IR (KBr): 3448, 2931, 2858, 1726, 1465, 1374, 1253, 1082, 838 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 9.77 (s, 1H), 5.89 (ddd, 17.4, 9.9, 7.8 Hz, 1H), 5.33 (d, J = 17.2 Hz, 1H), 5.26 (d, J = 10.2 Hz, 1H), 4.54 (t, J = 6.7 Hz, 1H), 4.10 (t, J = 7.2 Hz, 1H), 3.75 (dd, J = 7.2, 1.8 Hz, 1H), 2.80–2.72 (m, 1H), 2.45–2.40 (m, 1H), 2.38 (dd, J = 8.1, 1.5 Hz, 1H), 1.45 (s, 3H), 1.34 (s, 3H), 1.04 (d, J = 6.6 Hz, 3H), 0.89 (s, 9H), 0.10 (s, 3H), 0.06 (s, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 202.6, 134.7, 118.6, 108.3, 79.2, 79.1, 73.0, 47.2, 32.3, 28.0, 26.0, 25.4, 18.2, 15.3, −3.7, −4.2 ppm; MS m/z 365, [M + Na]⁺; HRMS calcd for C₁₈H₃₄O₄NaSi [M + Na]⁺ 365.2119, found 365.2117.

(2R,3R)-1-((6S,7aS)-8,8-Dimethyl-2,2-dioxidohexahydro-1H-3a,6-methanobenzo[c]isothiazol-1-yl)-3-hydroxy-2-methylbutan-1-one (13)

To a magnetically stirring solution of propionate 7 (5.00 g, 18.45 mmol) in CH₂Cl₂ (40 mL), triethylamine (2.82 mL, 20.30 mmol) followed by tert-butyldimethylsilyl-O-triflate (4.66 mL, 20.30 mL) were added at rt. Stirring was continued for 24 h, and the resulting solution was then added to a solution of acetaldehyde (1.14 mL, 20.30 mmol) and TiCl₄ (2.23 mL, 20.30 mmol) in CH₂Cl₂ (30 mL) at −78 °C. After 5 min, the reaction was quenched with sat. aq. NH₄Cl (20 mL), diluted with water (50 mL), and stirred at rt for 15 min. The organic layer was separated, and the aqueous layer was extracted with CH₂Cl₂ (2 × 20 mL). The combined organic layers were then washed with brine (20 mL), dried over anhydrous Na₂SO₄, filtered and concentrated under reduced pressure to give the crude product. Upon column purification (hexane–EtOAc, 5 : 1), the crude product gave unreacted propionate 7 (2.00 g) and finally alcohol 13 (3.42 g, 98% brsm) as a white solid (mp = 119–120 °C); R_f = 0.45 (hexane–EtOAc, 7 : 3); [α]²⁴_D = −46.17 (c 1.2, CHCl₃); IR (KBr): 3526, 2959, 1698, 1683, 1307, 1216, 1062 cm⁻¹; ¹H NMR (CDCl₃, 300 MHz): δ 3.90 (dd, J = 7.6, 5.1 Hz, 1H), 3.88–3.79 (m, 1H), 3.54 (d, J = 13.9 Hz, 1H), 3.45 (d, J = 13.9 Hz, 1H), 3.16–3.07 (m, 1H), 2.40–2.24 (m, 1H), 2.22–2.03 (m, 2H), 1.98–1.81 (m, 2H), 1.47–1.32 (m, 2H), 1.25 (d, J = 6.2 Hz, 3H), 1.21 (d, J = 6.6 Hz, 3H), 1.18 (s, 3H), 0.97 (s, 3H) ppm; ¹³C NMR (CDCl₃, 75 MHz): δ 175.1, 71.5, 65.3, 53.1, 48.2, 47.6, 46.9, 44.6, 38.4, 32.8, 26.3, 21.8, 20.7, 19.8, 14.0 ppm; MS m/z 316 [M + H]⁺; HRMS (ESI) for C₁₅H₂₆O₄NS [M + H]⁺ found 316.15682, calcd 316.15771.

(2R,3R)-3-((tert-Butyldimethylsilyl)oxy)-1-((6S,7aS)-8,8-dimethyl-2,2-dioxidohexahydro-1H-3a,6-methanobenzo[c]isothiazol-1-yl)-2-methylbutan-1-one (14)

To the stirring solution of alcohol 13 (4.00 g, 12.70 mmol) in CH₂Cl₂ (40 mL), lutidine (1.6 mL, 14.0 mmol) followed by TBSOTf (3.2 mL, 14.0 mmol) were added at 0 °C. Within 5 min, all the starting material was consumed. Sat. aq. NH₄Cl (10 mL) was added, and the reaction was diluted with water (30 mL). The organic layer was separated, and the aqueous layer was extracted with CH₂Cl₂ (2 × 20 mL). The combined organic layer was washed with brine (20 mL), dried over anhydrous Na₂SO₄, filtered and concentrated under reduced pressure to give the crude product. Upon column purification (hexane–EtOAc, 9 : 1), TBS ether 14 (4.9 g, 90%) was obtained as a white solid (mp = 129 °C); R_f = 0.5 (hexane–EtOAc 7 : 3); [α]²⁴_D = −8.0 (c 0.15, CHCl₃); IR (KBr): 2958, 2884, 1693, 1458, 1327, 1220, 1111, 837, 775 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 4.1–4.13 (m, 1H), 3.89–3.85 (m, 1H), 3.49 (d, J = 13.7 Hz, 1H), 3.41 (d, J = 13.7 Hz, 1H), 3.18–3.13 (m, 1H), 2.08–2.03 (m, 2H), 1.94–1.82 (m, 3H), 1.43–1.30 (m, 2H), 1.16 (s, 3H), 1.11 (d, J = 6.9 Hz, 3H), 1.10 (d, J = 6.3 Hz, 3H), 0.96 (s, 3H), 0.85 (s, 9H), 0.05 (s, 3H), 0.03 (s, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 174.4, 69.9, 65.4, 53.1, 48.0, 47.7, 44.7, 38.6, 32.8, 26.4, 25.7, 20.9, 20.0, 19.8, 17.9, 11.8, −4.6, −4.9 ppm; MS m/z 430 [M + H]⁺; HRMS calcd for C₂₁H₄₀O₄NSSi [M + H]⁺ 430.2441, found 430.2433.

(2S,3R)-3-((tert-Butyldimethylsilyl)oxy)-2-methylbutan-1-ol (15)

To the magnetically stirring suspension of LiAlH₄ (0.177 g, 4.66) in THF (20 mL), amide 14 (2.0 g, 4.66 mmol) was added at 0 °C. Within 5 min, all the starting material was consumed, and the reaction was quenched with sat. aq. Na₂SO₄ (5 mL). Silica gel (5.00 g) was added, and the resulting white suspension was further stirred at rt for 30 min and filtered. The filtrate was concentrated under reduced pressure to give the crude product. Upon column purification through a short pad of silica gel (hexane–EtOAc 9 : 1 to 5 : 1), the crude product gave free sultum auxiliary (0.97 g, 98%) and alcohol 15 (0.92 g, 90%) as a colorless oil; R_f = 0.4 (hexane–EtOAc, 7 : 3); [α]²⁴_D = +19.3 (c 0.2, CHCl₃); IR (KBr): 3420, 2957, 2858, 1468, 1377, 1254, 1033, 836, 775 cm^_1; ¹H NMR (500 MHz, CDCl₃): δ 3.85–3.73 (m, 2H), 3.54 (dd, J = 11.0, 5.9 Hz, 1H), 2.95 (br s, 1H), 1.66–1.52 (m, 1H), 1.21 (d, J = 6.2 Hz, 3H), 0.97 (d, J = 7.0 Hz, 3H), 0.89 (s, 9H), 0.10–0.08 (m, 6H) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 73.9, 65.7, 41.6, 25.7, 22.0, 17.8, 14.5, −4.3, −5.1 ppm; MS m/z 219 [M + H]⁺; HRMS calcd for C₁₁H₂₇O₂Si [M + H]⁺ 219.1774, found 219.1775.

5-(((2S,3S)-3-((tert-Butyldimethylsilyl)oxy)-2-methylbutyl)sulfonyl)-1-phenyl-1H-tetrazole (5)

PPh₃ (0.90 g, 3.44 mmol) and 1-phenyl-1H-tetrazole-5-thiol (0.61 g, 3.44 mmol) were added to a magnetically stirring solution of alcohol 15 (0.50 g, 2.29 mmol) in THF (20 mL) at 0 °C. Finally, diisopropylazodicarboxylate (0.70 mL, 3.44 mmol) was added at the same temperature. Within 30 min, all the starting material was consumed. THF was evaporated under reduced pressure, and the crude solid was purified by column chromatography (hexane–EtOAc 19 : 1) to give the sulfide 5a (0.82 g, 95%) as a colorless oil; R_f = 0.5 (hexane–EtOAc, 5 : 1); [α]²⁴_D = +19.9 (c 0.425, CHCl₃); IR (KBr): 2957, 2857, 1500, 1408, 1384, 1252, 1082, 835, 773 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.62–7.51 (m, 5H), 3.82–3.76 (m, 1H), 3.65 (dd, J = 12.7, 4.6 Hz, 1H), 3.26 (dd, J = 12.8, 8.1 Hz, 1H), 2.02–1.93 (m, 1H), 1.18 (d, J = 6.3 Hz, 3H), 1.04 (d, J = 6.9 Hz, 3H), 0.88 (s, 9H), 0.05 (s, 3H), 0.03 (s, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 154.9, 133.7, 129.9, 129.7, 123.8, 71.2, 40.1, 36.1, 25.7, 20.8, 17.9, 15.7, −4.3, −5.0 ppm; MS m/z 379 [M + H]⁺; HRMS calcd for C₁₈H₃₁ON₄SSi [M + H]⁺ 379.1982, found 379.1985.

To the magnetically stirring solution of sulfide 5a (1.0 g, 2.6 mmol) in EtOH (10 mL), a pre-cooled (0 °C) solution of ammonium molybdate tetrahydrate (1.6 g, 1.4 mmol) in 30% H₂O₂ (4 mL) was added at 0 °C. Stirring was continued until the starting material was completely consumed (ca. 12 h). Sat. aq. NaCl (10 mL) was added, and the organic layer was extracted with CH₂Cl₂ (4 × 10 mL). The combined organic layers were dried over anhydrous Na₂SO₄, filtered and concentrated under reduced pressure to give the crude product. Upon column purification (hexane–EtOAc, 9 : 1), sulfone 5 (0.89 g, 90%) was obtained as a colorless oil; R_f = 0.45 (hexane–EtOAc, 5 : 1); [α]²⁴_D = +10.1 (c 0.5, CHCl₃); IR (KBr): 2929, 2857, 1638, 1497, 1343, 1384, 1254, 1154, 837, 770 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 7.71–7.66 (m, 2H), 7.65–7.58 (m, 3H), 4.08 (dd, J = 14.8, 2.9 Hz, 1H), 3.83–3.77 (m, 1H), 3.45 (dd, J = 14.6, 9.5 Hz, 1H), 2.33–2.24 (m, 1H), 1.18 (d, J = 6.9 Hz, 3H), 1.18 (d, J = 6.3 Hz, 3H), 0.89 (s, 9H), 0.07 (s, 3H), 0.06 (s, 3H) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 154.0, 133.1, 131.4, 129.6, 125.1, 71.4, 57.9, 35.3, 25.8, 21.0, 17.9, 17.1, −4.3, −5.0 ppm; MS m/z 412 [M + H]⁺; HRMS calcd for C₁₈H₃₁O₃N₄SSi [M + H]⁺ 412.1904, found 412.1906.

(5S,6R,10R,11R,E)-11-((4S,5S)-2,2-Dimethyl-5-vinyl-1,3-dioxolan-4-yl)-2,2,3,3,5,6,10,13,13,14,14-undecamethyl-4,12-dioxa-3,13-disilapentadec-7-ene (3)

KHMDS (9.73 mL, 0.5 M in toluene, 4.87 mmol) was added dropwise to a stirring solution of sulfone 5 (1.0 g, 2.43 mmol) in dry THF (10 mL) at −78 °C. The resulting bright yellow solution was stirred at −78 °C for 1 h, and a solution of aldehyde 4 (0.84 g, 2.43 mmol) in dry THF (5 mL) was then added slowly from a syringe over 10 min. The reaction mixture was stirred at −78 °C for 1 h and then allowed to warm to rt over 1 h; all starting materials were consumed (monitored by TLC analysis) during this process. The reaction mixture was stirred in open air for 30 min, and all volatiles were then removed under reduced pressure. The obtained residue was purified by column chromatography (2% EtOAc–hexane) to give 3 as a colorless viscous oil (1.03 g, 80%); R_f = 0.3 (5% EtOAc–hexane); [α]²⁴_D = −23.18 (c 1.4, CHCl₃); IR (KBr): 2958, 2931, 2858, 1466, 1373, 1253, 1081, 837 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 5.99–5.89 (m, 1H), 5.41–5.31 (m, 2H), 5.31–5.257 (m, 1H), 5.21–5.19 (m, 1H), 4.53–4.47 (m, 1H), 4.12 (dd, J = 7.8, 5.6 Hz, 1H), 3.82 (dd, J = 7.9, 3.1 Hz, 1H), 3.71–3.66 (m, 1H), 2.33–2.26 (m, 1H), 2.16–2.09 (m, 1H), 1.95–1.87 (m, 1H), 1.80–1.72 (m, 1H), 1.46 (s, 3H), 1.34 (s, 3H), 1.03 (d, J = 6.1 Hz, 3H), 0.97 (d, J = 1.6 Hz, 3H), 0.96 (d, J = 1.6 Hz, 3H), 0.88 (s, 9H), 0.87 (s, 9H), 0.06–0.01 (m, 12H) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 135.4, 135.3, 129.3, 117.9, 108.0, 79.5, 78.8, 72.5, 72.0, 44.4, 39.0, 36.1, 28.2, 26.1, 25.9, 20.5, 18.3, 18.1, 16.1, 14.5, −3.7, −4.0, −4.4, −4.8 ppm; MS m/z 550 [M + Na]⁺; HRMS calcd for C₂₉H₅₈O₄NaSi₂ [M + Na]⁺ 549.3766, found 549.3758.

2-((4S,5S)-2,2-Dimethyl-5-((5R,6R,10R,11S,E)-2,2,3,3,6,10,11,13,13,14,14-undecamethyl-4,12-dioxa-3,13-disilapentadec-8-en-5-yl)-1,3-dioxolan-4-yl)ethanol (16)

Me₂S–BH₃ complex (0.03 mL, 0.29 mmol) was added dropwise to a stirring solution of cyclohexene (0.06 mL, 0.57 mmol) in THF (0.2 mL) at 0 °C. The resulting solution was stirred for 15 min, and a solution of compound 3 (100 mg, 0.19 mmol) in THF (2 mL) was then added at the same temperature. The solution was allowed to warm to rt, and all starting material was consumed within 1 h (reaction monitored by TLC). The reaction mixture was then treated with NaOH (3 N, 2 mL) followed by H₂O₂ (30%, 2 mL) at 0 °C and stirred for 2 h. The reaction mixture was extracted with EtOAc (3 × 5 mL), and the combined extracts were washed with brine (10 mL) solution, dried over anhydrous Na₂SO₄ and concentrated. the resultant residue was purified by silica gel column chromatography (EtOAc–hexane, 1 : 9) to afford 16 (72.6 mg, 70%) as a colorless oil; R_f = 0.5 (hexane–EtOAc, 8 : 2); [α]²⁴_D = −21.15 (c 1.4, CHCl₃); IR (KBr): 3448, 2939, 1463, 1375, 1220, 1079, 838 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 5.41–5.31 (m, 2H), 4.29 (ddd, J = 11.4, 5.2, 2.1 1H), 4.08 (dd, J = 8.1, 5.3 Hz, 1H), 3.88–3.79 (m, 3H), 3.72–3.66 (m, 1H), 2.56 (br s, 1H), 2.32–2.24 (m, 1H), 2.16–2.09 (m, 1H), 1.97–1.89 (m, 1H), 1.84–1.73 (m, 2H), 1.71–1.58 (m, 1H), 1.46 (s, 3H), 1.33 (s, 3H), 1.03 (d, J = 6.1 Hz, 3H), 0.99–0.95 (m, 6H), 0.88 (s, 9H), 0.86 (s, 9H), 0.08 (s, 3H), 0.05 (s, 3H), 0.04–0.02 (m, 6H) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 134.5, 129.1, 108.2, 78.4, 77.8, 72.4, 72.0, 61.7, 44.4, 39.0, 36.0, 32.1, 28.4, 25.9 (2C), 20.5, 18.2, 18.1, 16.2, 14.5, −3.6, −4.3, −4.4, −4.8 ppm; MS m/z 567 [M + Na]⁺; HRMS calcd for C₂₉H₆₀O₅NaSi₂ [M + Na]⁺ 567.3874, found 567.3874.

2-((4S,5S)-2,2-Dimethyl-5-((5R,6R,10R,11S,E)-2,2,3,3,6,10,11,13,13,14,14-undecamethyl-4,12-dioxa-3,13-disilapentadec-8-en-5-yl)-1,3-dioxolan-4-yl)acetic acid (17)

A mixture of 16 (100 mg, 0.18 mmol), [bis(acetoxy)-iodo]benzenze (BAIB; 236 mg, 0.73 mmol) and 2,2,6,6-tetramethyl-1-piperidinyloxyl (TEMPO; 14.33 mg, 0.09 mmol) were stirred in CH₃CN (1.5 mL) and H₂O (0.5 mL) at rt for 2 h. The solution was quenched with 2 mL hypo solution and extracted with AcOEt (3 × 5 mL). After concentration under reduced pressure, the obtained residue was purified by column chromatography on silica gel (3 : 2 hexane–AcOEt) to afford compound 17 as a colorless viscous oil (90.1 mg, 88%); R_f = 0.5 (EtOAc–hexane, 1 : 1); [α]²⁴_D = −38.8 (c 0.2, CHCl₃); IR (KBr): 3448, 2956, 2929, 1712, 1465, 1377, 1253, 1080, 836 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 5.42–5.31 (m, 2H), 4.55 (ddd, J = 10.7, 4.9, 3.1 Hz, 1H), 4.14 (dd, J = 7.3, 5.2 Hz, 1H), 3.79 (dd, J = 7.5, 3.5 Hz, 1H), 3.72–3.66 (m, 1H), 2.64–2.50 (m, 2H), 2.29–2.24 (m, 1H), 2.17–2.10 (m, 1H), 1.94–1.89 (m, 1H), 1.80–1.70 (m, 1H), 1.47 (s, 3H), 1.34 (s, 3H), 1.04 (d, J = 6.1 3H), 0.97 (d, J = 5.5 Hz, 3H), 0.96 (d, J = 5.3 Hz, 3H), 0.88 (s, 9H), 0.87 (s, 9H), 0.08 (s, 3H), 0.07 (s, 3H), 0.04–0.02 (m, 6H) ppm; ¹³C NMR (75 MHz, CDCl₃): δ 176.4, 134.7, 128.7, 108.6, 77.1, 74.7, 72.6, 71.9, 44.4, 38.9, 36.7, 36.2, 28.5, 25.9 (2C), 20.6, 18.2, 18.1, 16.3, 14.5, −3.7, −4.3, −4.4, −4.8 ppm; MS m/z 567 [M + Na]⁺; HRMS calcd for C₂₉H₅₈O₆NaSi₂ [M + Na]⁺ 581.3664, found 581.3669.

Mupirocin H (2)

Concentrated HCl (0.2 mL) was added to a stirring solution of acid 17 (40 mg, 0.07 mmol) in THF (5 mL), and the resulting solution was stirred at 65 °C for 6 h. The reaction mixture was diluted with CH₂Cl₂ (10 mL) and sat. aq. NaCl solution (10 mL). The organic layer was separated, and the aqueous layer was extracted with 10% MeOH–CH₂Cl₂ (4 × 10 mL). The combined organic layer was dried over anhydrous Na₂SO₄ and concentrated in vacuo. Purification by silica gel column chromatography (MeOH–CH₂Cl₂, 1 : 19) afforded mupirocin H 2 (16.55 mg, 85%) as a colorless oil; R_f = 0.3 (MeOH–CH₂Cl₂ 1 : 9); [α]²⁴_D = +23.3 (c 0.4, CHCl₃); IR (KBr): 3419, 2926, 2855, 1771, 1456, 1377, 1067, 771 cm⁻¹; ¹H NMR (500 MHz, CDCl₃): δ 5.61 (ddd, J = 15.0, 8.2, 6.3 Hz, 1H), 5.39 (dd, J = 15.4, 8.7 Hz, 1H), 4.62–4.56 (m, 1H), 4.42 (dd, J = 5.6, 3.2 Hz, 1H), 3.60–3.56 (m, 1H), 3.54–3.48 (m, 1H), 2.93 (dd, J = 18.2, 7.5 Hz, 1H), 2.52 (dd, J = 18.2, 4.4 Hz, 1H), 2.30–2.20 (m, 2H), 2.10–2.02 (m, 1H), 1.94–1.84 (m, 1H), 1.18 (d, J = 6.1 Hz, 3H), 1.05 (d, J = 7.0 Hz, 3H), 0.98 (d, J = 6.9 Hz 3H); ¹³C NMR (75 MHz, CDCl₃): δ 175.8, 134.7, 129.5, 87.6, 75.1, 71.5, 68.4, 45.2, 38.2, 35.2, 34.5, 20.5, 16.8, 15.9 ppm; MS m/z 295 [M + Na]⁺; HRMS calcd for C₁₄H₂₄O₅Na [M + Na]⁺ 295.1495, found 295.1516.

Acknowledgements

YS thanks CSIR, New Delhi for financial assistance in the form of a fellowship. NHK thanks NIPER, Hyderabad for financial assistance in the form of a fellowship. PSH acknowledges funding from CSIR, New Delhi as part of the XII Five year plan program under title ORIGIN (CSC-108) and research grant (P-81-113) from the Human Resources Research Group-New Delhi through the Council of Scientific & Industrial Research (CSIR) Young Scientist Award Scheme. This paper is dedicated to Dr. J. S. Yadav on the occasion of his 64th birthday.

Notes and references

1. M. H. Wilcox, J. Hall, H. Pike, P. A. Templeton, W. N. Fawley, P. Parnell and P. Verity, J. Hosp. Infect., 2003, 54, 196–201.
2. S. M. Cooper, R. J. Cox, J. Crosby, M. P. Crump, J. Hothersall, W. Laosripaiboon, T. J. Simpson and C. M. Thomas, Chem. Commun., 2005, 1179–1181.
3. J. Wu, S. M. Cooper, R. J. Cox, J. Crosby, M. P. Crump, J. Hothersall, T. J. Simpson, C. M. Thomas and C. L. Willis, Chem. Commun., 2007, 2040–2042.
4. (a) Y. J. Class and P. DeShong, Chem. Rev., 1995, 95, 1843 and references cited therein; (b) C. McKay, T. J. Simpson, C. L. Willis, A. K. Forrest and P. J. O’Hanlon, Chem. Commun., 2000, 1109; (c) T. Honda and N. Kimura, Org. Lett., 2002, 4, 4567; (d) X. Gao and D. G. Hall, J. Am. Chem. Soc., 2005, 127, 1628; (e) L. van Innis, J. M. Plancher and I. E. Marko, Org. Lett., 2006, 8, 6111; (f) R. F. de la Pradilla and N. Lwoff, Tetrahedron Lett., 2008, 49, 4167; (g) R. F. de la Pradilla, N. Lwoff and A. Viso, Eur. J. Org. Chem., 2009, 2312; (h) S. P. Udawant and T. K. Chakraborty, J. Org. Chem., 2011, 76, 6331; (i) R. W. Scott, C. Mazzetti, T. J. Simpson and C. L. Willis, Chem. Commun., 2012, 48, 2639.
5. (a) S. Udawant and T. K. Chakraborty, J. Org. Chem., 2011, 76, 6331–6337; (b) R. W. Scott, C. Mazzetti, T. J. Simpson and C. L. Willis, Chem. Commun., 2012, 48, 2639–2641; (c) C. Zhao, Z. Yuan, Y. Zhang, B. Ma, H. Li, S. Tang, X. Xie and X. She, Org. Chem. Front., 2014, 1, 105–108.
6. (a) Y. Sridhar and P. Srihari, Org. Biomol. Chem., 2013, 11, 4640–4645; (b) Y. Sridhar and P. Srihari, Eur. J. Org. Chem., 2013, 578–587; (c) P. Srihari, A. Sathish Reddy, J. S. Yadav, D. Yedlapudi and V. S. Kalivendi, Tetrahedron Lett., 2013, 54, 5616–5618; (d) P. Srihari and Y. Sridhar, Eur. J. Org. Chem., 2011, 6690–6697; (e) P. Srihari, K. Satyanarayana, B. Ganganna and J. S. Yadav, J. Org. Chem., 2011, 76, 1922–1925.
7. Y. Sridhar and P. Srihari, Org. Biomol. Chem., 2014, 12, 2950–2959.
8. P. Srihari, B. Kumaraswamy and J. S. Yadav, Tetrahedron, 2009, 65, 6304–6309.
9. The same product was synthesized in 5 steps starting from d-ribose. See L.-S. Li and D.-R. Hou, RSC Adv., 2014, 4, 91–97.
10. (a) K. Omura and D. Swern, Tetrahedron, 1978, 34, 1651–1660; (b) K. Vamshikrishna and P. Srihari, Tetrahedron, 2012, 68, 1540–1546.
11. T. Andreou, A. M. Costa, L. Esteban, L. Gonzalez, G. Mas and J. Vilarrasa, Org. Lett., 2005, 7, 4083–4086.
12. S. R. Harutyunyan, T. d. Hartog, K. Geurts, A. J. Minnaard and B. L. Feringa, Chem. Rev., 2008, 108, 2824–2852 and references cited there in.
13. A. S. Kireev, M. Manpadi and A. Kornienko, J. Org. Chem., 2006, 71, 2630–2640.
14. (a) D. B. Dess and J. C. Martin, J. Am. Chem. Soc., 1991, 113, 7277–7287; (b) J. S. Yadav and P. Srihari, Tetrahedron: Asymmetry, 2004, 15, 81–89.
15. (a) W. Oppolzer, J. Blagg, I. Rodriguez and E. Walther, J. Am. Chem. Soc., 1990, 112, 2767–2772; (b) W. Oppolzer, C. Starkemann, I. Rodriguez and G. Bernardinelli, Tetrahedron Lett., 1991, 32, 61–64 . Procedure was followed from ref. 7.
16. O. Mitsunobu, Synthesis, 1981, 1–28.
17. (a) J. B. Baudin, G. Hareau, S. A. Julia and O. Ruel, Tetrahedron Lett., 1991, 32, 1175–1178; (b) C. Aïssa, Eur. J. Org. Chem., 2009, 1831–1844.
18. S. K. Kang, K. Y. Jung, J. U. Chung, E. Y. Namkoong and T. H. Kim, J. Org. Chem., 1995, 60, 4678–4679.
19. Initial attempts with BH₃·DMS and 9-BBN ended with recovery of the starting material.
20. (a) H. C. Brown, A. K. Mandal and S. U. Kulkarni, J. Org. Chem., 1977, 42, 1392–1398; (b) M. M. Midland and Y. C. Kwon, J. Am. Chem. Soc., 1983, 105, 3725–3727.
21. J. B. Epp and T. S. Widlanski, J. Org. Chem., 1999, 64, 293–295.

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Footnote

† Electronic supplementary information (ESI) available: ¹H NMR and ¹³C NMR copies of new compounds. See DOI: 10.1039/c4ra06373b

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