Exploring Acetylene Chemistry: A Transition Metal-Free Route to

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Exploring acetylene chemistry: A Transition Metal-Free Route to Dienyl 6,8-DOBCOs from Ketones and Acetylenes Elena Yu Schmidt, Inna V. Tatarinova, Nadezhda V. Semenova, Nadezhda I. Protsuk, Igor A. Ushakov, and Boris A. Trofimov J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01449 • Publication Date (Web): 20 Jul 2018 Downloaded from http://pubs.acs.org on July 20, 2018

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The Journal of Organic Chemistry

Exploring Acetylene Chemistry: A Transition Metal-Free Route to Dienyl 6,8-DOBCOs from Ketones and Acetylenes Elena Yu. Schmidt, Inna V. Tatarinova, Nadezhda V. Semenova, Nadezhda I. Protsuk, Igor’ A. Ushakov and Boris A. Trofimov*

A. E. Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 1 Favorsky Str., 664033 Irkutsk, Russia

E-mail: [email protected] Graphical abstract

ABSTRACT Dienyl derivatives of 6,8-dioxabicyclo[3.2.1]octanes, closely related to naturally abundant molecules, have been synthesized from 2-acetyl-3,4-dihydropyrans (readily available from ketones and acetylene in two steps), which further add to aryl(hetaryl)acetylenes in the KOBut/DMSO superbase system (105 oC, 1.5 h) to stereoselectively give the corresponding Estyryl adducts. The latter undergo ring closure (NH4Cl/H2O, acetonitrile, reflux, 8 h) to form 6,8dioxabicyclo[3.2.1]octane core decorated with (1Z, 3E)-diene substituent. INTRODUCTION

The bridgehead bicyclic acetal architectures, 6,8-dioxabicyclo[3.2.1]octanes (commonly abbreviated as 6,8-DOBCOs), represent a naturally abundant scaffold met in the molecules of insect pheromones (frontalin,1 brevicomin,1a,2 multistriatin1a,2b,3), mammal hormones4 and marine toxins.5 Some 6,8-DOBCOs are found to possess anticancer6 and antiviral7 activity. Therefore, the interest in this class of compounds keeps steadily growing and novel approaches to their synthesis warranting structural diversity are in-demand. However, the existing protocols are mostly multistep, transition-metal-catalyzed and require hardly accessible polyfunctional starting materials, e.g. δ-keto diols, δ-keto epoxides, diazo ketones, etc (see, for example, the recent review).8 Thus, the search for simpler, more expedient, and transition-metal-free strategies for the design of 6,8-DOBCOs remains a challenge. 1 ACS Paragon Plus Environment

The Journal of Organic Chemistry 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60

Recently, we have discovered the superbase-catalyzed one-pot diastereoselective selforganization of two molecules of ketones with two molecules of acetylene to 7-methylene-6,8DOBCOs 1 (Scheme 1, eq 1)9 thereby opening up fresh opportunities for further development of these bicyclic acetals chemistry. Compounds 1 appear to be quantitatively isomerized under the action of an acid catalyst to 2-acetyl-3,4-dihydropyrans 2 (Scheme 1, eq 2).10 Also, the dehydrative rearrangement of 6,8-DOBCOs 1 to acylcyclopentadienes (Scheme 1, eq 2)11 and the click thiol addition12 to their double bond have been realized. In turn, 2-acetyl-3,4dihydropyrans 2 are transformed into 1,6-dioximes13 and their deacetylation to another series of dihydropyrans14 is implemented (Scheme 1, eq 3).

Scheme 1. Previous and Present Works

Here we report acetylene-based two-step stereoselective synthesis of dienyl derivatives of 6,8-DOBCOs 5 that includes the superbase-promoted C-vinylation of 2-acetyl-3,4-dihydropyrans 2 with aryl(hetaryl)acetylenes 3 and acid-catalyzed ring closure of adducts 4 to form the bicyclic acetals 5 (Scheme 1, eq 4).

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RESULTS AND DISCUSSION

The C-vinylation of dihydropyrans 2 with aryl(hetaryl)acetylenes 3 proceeds upon their heating in the KOBut/DMSO superbase system to afford the E-styryl derivatives 4 in 72-83% yields (Table 1). The narrow range of the yields shows a weak dependence of the reaction efficiency on the reactant structure, both dihydropyrans 2 and acetylenes 3. Table 1. Substrate Scope of C-Vinylation of 3,4-Dihydropyrans 2 with Acetylenes 3a

dihydropyran

acetylene

product, yield (%)b

2a

3a

4a, 76%

2a

3b

4b, 73%

2a

3c

4c, 72%

2a

3d

4d, 79%

2a

3e

4e, 82%

2a

3f

4f, 74%

2b

3a

4g, 82%



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2b

3c

4h, 79%

2b

3d

4i, 83%

2b

3f

4j, 77%

2c

3a

4k, 76%

2d

3c

4l, 73%

2e

3a

6a, 79% (dr ~ 1:1)c Me

O

2f a b

3a

6b, 81% (dr ~ 2:1)c

Reaction conditions: 2 (2 mmol), 3 (2 mmol), KOBut (2 mmol, 224 mg), DMSO (10 mL). Yields after column chromatography (Al2O3, hexane) are given. cdr = diastereomeric ratio. The reaction conditions can be considered as provisionally optimum since they have been

selected from a series of experiments carried out at varied temperatures, reactant/catalyst ratios and the process duration. Typical features of the optimization process conducted for the reaction 2a+3a to give dihydropyran 4a are shown in Table 2. Astonishingly, that in contrast to KOBut, KOH appears to be absolutely inactive as a catalyst in this reaction (entry 1).


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Table 2. Optimization of the Reaction Conditions for the Synthesis of Dihydropyran 4aa

entry base temp (oC) time (h) 2a:4ab yield of 4a (%)c 1 KOH 100 1.5 1:0 0 2 KOBut 100 1.0 1:4 51 3 KOBut 100 1.5 1:10 65 t 4 KOBu 105 1.5 0:1 76 a Reaction conditions: 2a (2 mmol, 585 mg), 3a (2 mmol, 204 mg), base (2 mmol), DMSO (10 mL). bMolar ratio according to 1H NMR spectra of the crude product. cAfter column chromatography (Al2O3, hexane). The best acetylenic substrates for the vinylation of acetyldihydropyrans 2 are alkynylarenes 3 (Table 1), while aliphatic acetylenes appeared to be unsuitable for this reaction because under strongly basic conditions they readily undergo acetylene-allene prototropic isomerization or are not electrophilic enough (e.g. tert-butylacetylene) towards carbanions of ketones 2. At the same time, the reactant scope is obviously not extendable over some strongly electrophilic acetylenes such as propiolates and the like due to the side transformations of the functional groups or their anionic oligomerization. The structure variation of acetyldihydropyrans 2 are represented by aromatic and tertalkyl groups, which cover a large range of organic substituents though there are no obvious fundamental obstacles for primary and secondary alkyls to be involved in this reaction. The C-vinylation represents a nucleophilic addition of the carbon-centered nucleophiles to acetylenic moiety: the carbanions A generated by deprotonation of the acetyl group under the action of superbase (KOBut/DMSO) regio- and stereoselectively attack the triple bond (Scheme 2).15 Scheme 2. C-Vinylation of 2-Acetyl-3,4-Dihydropyrans 2

Commonly, such nucleophilic addition to acetylenes stereoselectively leads to the Zadducts (trans-addition rule).16 The inversion of the stereoselectivity in this case is evidently due to a steric repulsion between the densely substituted 3,4-dihydropyran moiety and aryl group of acetylene. 5 ACS Paragon Plus Environment


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The E configuration of adducts 4 has been unambiguously established by 3JH-H values (15.8-16.1 Hz) between protons at the double bond in the 1H NMR spectra (see Experimental Section). In the case of bulky substituents (e.g. 4-PhC6H4, 2-naphthyl) adjacent to the acetyl group, the vinylation does not occur (Table 1, substrates 2e,f) obviously due to the steric shielding of the reacting carbanion. Here, instead of C-vinylation, the loss of the acetyl group with releasing of dihydropyrans 6a,b is observed. This side reaction and its tentative mechanism were considered previously.14 When dihydropyrans 4 are refluxed in the presence of 1.5 equiv of NH4Cl in aqueous acetonitrile, the ring closure takes place to form dienyl derivatives 5 (Scheme 3). This rearrangement occurs also in anhydrous acidic conditions, but not as clean as with the system NH4Cl/H2O/MeCN (small amounts of side products are detectable in 1H NMR spectra). Scheme 3. Cyclization of Dihydropyrans 4 to DOBCOs 5a,b

5a, 71%

5b, 68%

5c, 66%

5d, 66%

5e, 56%

5f, 53%

5g, 75%

5h, 71%

5i, 63%

5j, 69%

5k, 60%

5l, 57%

Me

O Ph

Me

O

Me


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a

Reaction conditions: 4 (1 mmol), NH4Cl (1.5 mmol, 80 mg), H2O (1.5 mL), MeCN (7.5 mL). bYields after column chromatography (Al2O3, hexane) are given. A general impression about the influence of the reaction conditions on dihydropyran 4a cyclization can be drawn from Table 3. As mentioned above, although some acids catalyze the cyclization, the most selective and efficient catalyst proved to be aqueous NH4Cl that is rationalized below.

Table 3. Influence of the Reaction Conditions on Cyclization of Dihydropyran 4a to DOBCO 5aa

4a:acid molar 4a:5a molar time (h) ratio ratiob 1 HClc 1:1 8 1.5:1 2 MeCOOH 1:1 6 1:0 3 CF3COOH 2:1 8 5:1 4 CF3COOH 1:1 2 3:1 5 CF3COOH 1:1 8 3:1d 6 NH4Cl/H2Oe 1:1.5 8 0:1 (71%)f a Reaction conditions: 4a (1 mmol, 395 mg), acid, MeCN (7.5 mL). b According to 1H NMR spectra of crude product. c0.36 mL of 10% aqueous HCl was used. dResinification of the reaction mixture was observed. eNH4Cl (1.5 mmol, 80 mg), H2O (1.5 mL). fYield of 5a after column chromatography (Al2O3, hexane). entry

acid

Structures of compounds 5 have been unambiguously established by NMR spectra using COSY, NOESY, 1H-13C HSQC and 1H-13C HMBC experiments (Figure 1, see Supporting Information (SI) for details).

Figure 1. Main NOESY correlations for compound 5k



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The isomerization of dihydropyrans 4 into isomers 5 apparently starts with their enolization (Scheme 4). The enol B undergoes intramolecular addition to the dihydropyran double bond through carbocation C, which, after the ring closure (involving the OH group) and release of the proton, delivers the final product 5. The diastereoselectivity of closing bicycle 5 is predetermined by the cyclic structure of the starting dihydropyran 4, in which the hydroxyl group can attack the position 6 only from axial direction that leads to just a single configuration of the carbon-6. Scheme 4. Plausible Mechanism of the Isomerization

Apparently, NH4Cl plays a role of bifunctional catalyst, not only protonating the carbonyl function, but also facilitating the proton elimination from neighboring CH2 group of the cation C. A striking feature of this isomerization is that it is the reverse reaction relative to 1 → 2 rearrangement (Scheme 1, eq 2), which very rapidly and completely occurs in the presence of trace acids.10 Evidently, this unexpected transformation is due to energy gain in the extended conjugation system (het)aryl–CH=CH–CH=C–O that is absent in DOBCOs 1. In summary, we have developed acetylene-based facile transition-metal-free route to previously inaccessible diversely substituted dienyl derivatives of 6,8-dioxabicyclo[3.2.1]octanes (6,8-DOBCOs). The synthesis involves the following two steps: (i) the base-catalyzed addition of

2-acetyl-3,4-dihydropyrans

(readily

available

from

ketones

and

acetylene)

to

aryl(hetaryl)acetylenes and (ii) ring closure of the formed E-styryl derivatives under mild conditions. Simple precursors (ketones and acetylenes) and simple protocol developed herein make the methodology practically feasible for the synthesis of previously unknown congeners of insect pheromones, mammal hormones and marine toxins as well as attractive building blocks for the design of naturally related molecular architectures.

EXPERIMENTAL SECTION 8 ACS Paragon Plus Environment

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General Remarks. 1Н (400.1 MHz) and 13С (100.6 MHz) NMR spectra were recorded in C6D6 (for 4a-l) or in СDСl3 (for 5a-l, 6a,b) with hexamethyldisiloxane (HMDS) as an internal standard. Chemical shifts (δ) are given in ppm, coupling constants (J) in Hz. The 1H and

13

C

chemical shifts (δ) were referenced to HMDS (0.05 ppm and 2.0 respectively). The assignment of signals in the 1Н NMR spectra was made using COSY and NOESY experiments. Resonance signals of carbon atoms were assigned based on 1H-13C HSQC and 1H-13C HMBC experiments. Coupling constants (J) were measured from one-dimensional spectra and multiplicities were abbreviated as following: s (singlet), d (doublet), dd (doublet of doublets), dt (doublet of triplets), m (multiplet). IR spectra were taken with FT-IR. Melting points (uncorrected) were measured on a Kofler micro hot-stage apparatus. The microanalyses were performed on a Flash EA 1112 Series elemental analyzer. Thin layer chromatography was carried out on Merck silica gel 60 F254 pre-coated aluminium foil sheets (eluent Et2O/hexane = 1 : 3) and were visualized using UV light (254 nm). Column chromatography was carried out using basic Al2O3 (eluent hexane). Starting Materials. 6,8-DOBCOs 1 were synthesized by published procedures from ketones and acetylene in the KOH/DMSO system.9 2-Acetyl-3,4-dihydropyrans 2 were prepared by the TFAcatalyzed rearrangement of the 6,8-DOBCO 1 according to the literature procedure.10 All other chemicals and solvents are commercially available and were used without further purification. General Procedure for the Synthesis of Dihydropyrans 4 and 6. A mixture of 2-acetyl-3,4dihydropyran 2 (2 mmol), arylacetylene 3 (2 mmol) and KOBut (2 mmol, 224 mg) in DMSO (10 mL) was stirred at 105 oC for 1.5 h. The reaction mixture, after cooling (rt), was diluted with H2O (15 mL) and extracted with Et2O (7 mL × 4). The organic extract was washed with H2O (5 mL × 3) and dried (K2CO3). Et2O was evaporated in vacuum and the residue was purified by column chromatography (basic Al2O3, eluent hexane). (E)-1-((2S*,4S*)-4-Methyl-2,6-diphenyl-3,4-dihydro-2H-pyran-2-yl)-4-phenylbut-3-en-1-one (4a). Following general procedure, 4a was prepared from dihydropyran 2a (585 mg, 2 mmol) and acetylene 3a (204 mg, 2 mmol). 4a was isolated as a yellow oil (600 mg, 76% yield). Anal. Calcd for C28H26O2: C, 85.25; H, 6.64. Found: C, 85.27; H, 6.63. IR (film): ν 3032, 1954, 1886, 1807, 1718, 1654, 1105, 965; 1H NMR (С6D6): δ 7.76-7.70 (m, 2H, Ho), 7.69-7.64 (m, 2H, Ho), 7.25-7.15 (m, 2H), 7.15-7.06 (m, 4H), 7.05-6.99 (m, 3H), 6.95-6.85 (m, 2H) [HPh], 6.14 (dt, 3J = 15.9 Hz, 3J = 8.0 Hz, 1H, Hβ), 5.90 (d, 3J = 15.9 Hz, 1H, Hγ), 5.19-5.17 (m, 1H, H5), 3.36 (d, 3J = 8.0 Hz, 2H, Hα), 2.86 (dd, 2J = 13.4 Hz, 3J = 6.5 Hz, 1H, 3-CH2), 2.61-2.48 (m, 1H, H4), 1.26 (dd, 2J = 13.4 Hz, 3J = 11.1 Hz, 1H, 3-CH2), 0.78 (d, 3J = 6.9 Hz, 3H, Me);

13

C{1H} NMR

(С6D6): δ 208.6 (C=O), 149.4 (C6), 140.3, 137.5, 135.8, 133.5, 129.0, 128.7, 128.6, 127.4, 125.4, 9 ACS Paragon Plus Environment


125.2, 124.8 (18CPh), 126.5 (Cβ), 122.6 (Cγ), 105.7 (C5), 87.6 (C2), 40.8 (Cα), 40.0 (C3), 25.4 (C4), 21.1 (Me). (E)-1-((2S*,4S*)-4-Methyl-2,6-diphenyl-3,4-dihydro-2H-pyran-2-yl)-4-(p-tolyl)but-3-en-1-one (4b). Following general procedure, 4b was prepared from dihydropyran 2a (585 mg, 2 mmol) and acetylene 3b (232 mg, 2 mmol). 4b was isolated as a yellow oil (597 mg, 73% yield). Anal. Calcd for C29H28O2: C, 85.26; H, 6.91. Found: C, 85.29; H, 6.99. IR (film): ν 3029, 1955, 1897, 1718, 1653, 1106, 966; 1H NMR(С6D6): δ 7.76-7.70 (m, 2H, Ho), 7.69-7.64 (m, 2H; Ho), 7.257.15 (m, 2H), 7.14-7.09 (m, 3H), 7.05-6.99 (m, 1H), 6.95-6.89 (m, 2H), 6.83-6.76 (m, 2H) [HPh], 6.15 (dt, 3J = 15.9 Hz, 3J = 7.0 Hz, 1H, Hβ), 5.93 (d, 3J = 15.9 Hz, 1H, Hγ), 5.19-5.16 (m, 1H, H5), 3.38 (d, 3J = 7.0 Hz, 2H, Hα), 2.87 (dd, 2J = 13.6 Hz, 3J = 6.6 Hz 1H, 3-CH2), 2.59-2.49 (m, 1H; H4), 1.98 (s, 3H, Me), 1.28 (dd, 2J = 13.6 Hz, 3J = 11.3 Hz, 1H, 3-CH2), 0.80 (d, 3J = 7.0 Hz, 3H, 4-Me); 13C{1H} NMR (С6D6): δ 208.7 (C=O), 149.4 (C6), 140.4, 136.8, 135.8, 134.9, 133.5, 129.3, 129.1, 129.0, 128.8, 128.7, 128.5, 125.2, 124.8 (18CPh), 126.5 (Cβ), 121.5 (Cγ), 105.7 (C5), 87.6 (C2), 40.9 (Cα), 40.0 (C3), 25.4 (C4), 21.1 (Me, 4-Me). (E)-4-([1,1'-Biphenyl]-4-yl)-1-((2S*,4S*)-4-methyl-2,6-diphenyl-3,4-dihydro-2H-pyran-2-yl)but3-en-1-one (4c). Following general procedure, 4c was prepared from dihydropyran 2a (585 mg, 2 mmol) and acetylene 3c (356 mg, 2 mmol). 4c was isolated as a yellow oil (678 mg, 72% yield). Anal. Calcd for C34H30O2: C, 86.77; H, 6.43. Found: C, 86.31; H, 6.43. IR (film): ν 3031, 1900, 1716, 1652, 1100, 974; 1H NMR (С6D6): δ 7.75-7.70 (m, 2H, Ho), 7.69-7.64 (m, 2H; Ho), 7.38-7.31 (m, 2H), 7.27-7.21 (m, 2H), 7.20-7.15 (m, 2H), 7.15-6.96 (m, 9H) [HPh], 6.19 (dt, 3J = 16.1 Hz, 3J = 7.0 Hz, 1H, Hβ), 5.93 (d, 3J = 16.1 Hz, 1H, Hγ), 5.18-5.17 (m, 1H, H5), 3.39 (d, 3J = 7.0 Hz, 2H, Hα), 2.87 (dd, 2J = 13.4 Hz, 3J = 6.5 Hz 1H, 3-CH2), 2.59-2.49 (m, 1H; H4), 1.27 (dd, 2

J = 13.4 Hz, 3J = 11.1 Hz, 1H, 3-CH2), 0.77 (d, 3J = 7.0 Hz, 3H, Me); 13C{1H} NMR (С6D6): δ

208.6 (C=O), 149.4 (C6), 141.3, 140.4, 136.5, 135.8, 133.1, 130.0, 129.3, 129.0, 128.9, 128.8, 128.6, 127.4, 127.3, 127.2, 127.1, 125.4, 125.2, 124.8 (24CPh), 127.0 (Cβ), 122.7 (Cγ), 105.7 (C5), 87.7 (C2), 41.0 (Cα), 40.0 (C3), 25.4 (C4), 21.1 (Me). (E)-4-(3-Methoxyphenyl)-1-((2S*,4S*)-(4-methyl-2,6-diphenyl-3,4-dihydro-2H-pyran-2-yl)but-3en-1-one (4d). Following general procedure, 4d was prepared from dihydropyran 2a (585 mg, 2 mmol) and acetylene 3d (264 mg, 2 mmol). 4d was isolated as a yellow oil (671 mg, 79% yield). Anal. Calcd for C29H28O3: C, 82.05; H, 6.65. Found: C, 82.02; H, 6.61. IR (film): ν 3033, 1955, 1891, 1808, 1717, 1653, 1104, 964; 1H NMR (С6D6): δ 7.77-7.75 (m, 2H, Ho), 7.71-7.69 (m, 2H, Ho), 7.23-7.14 (m, 2H), 7.11-7.06 (m, 2H), 7.04-7.00 (m, 1H), 6.99-6.91 (m, 2H), 6.70-6.59 (m, 3H) [HPh], 6.21 (dt, 3J = 15.9 Hz, 3J = 7.3 Hz, 1H, Hβ), 5.92 (d, 3J = 15.9 Hz, 1H, Hγ), 5.20-5.18 (m, 1H, H5), 3.39 (d, 3J = 7.3 Hz, 2H, Hα), 3.20 (s, 3H, OMe), 2.89 (dd, 2J = 13.3 Hz, 3J = 6.5 Hz 10 ACS Paragon Plus Environment

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1H, 3-CH2), 2.60-2.52 (m, 1H; H4), 1.29 (dd, 2J = 13.3 Hz, 3J = 11.4 Hz, 1H, 3-CH2), 0.80 (d, 3J = 6.9 Hz, 3H, Me);

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C{1H} NMR (С6D6): δ 208.6 (C=O), 160.3 (C-OMe), 149.4 (C6), 140.3,

139.0, 135.8, 133.6, 129.6, 129.0, 128.7, 128.6, 127.4, 125.4, 124.8 (14CPh), 125.2 (Cβ), 122.7 (Cγ), 119.2, 113.6, 111.7 (3CPhOMe), 105.7 (C5), 87.6 (C2), 54.6 (OMe), 40.9 (Cα), 40.0 (C3), 25.4 (C4), 21.1 (Me). (E)-4-(4-Fluorophenyl)-1-((2S*,4S*)-(4-methyl-2,6-diphenyl-3,4-dihydro-2H-pyran-2-yl)but-3en-1-on (4e). Following general procedure, 4e was prepared from dihydropyran 2a (585 mg, 2 mmol) and acetylene 3e (240 mg, 2 mmol). 4e was isolated as a yellow oil (677 mg, 82% yield). Anal. Calcd for C28H25FO2: C, 81.53; H, 6.11; F, 4.61. Found: C, 81.50; H, 6.03; F, 4.49. IR (film): ν 3040, 1957, 1889, 1719, 1654, 1102, 967; 1H NMR (С6D6): δ 7.76-7.70 (m, 2H, Ho), 7.69-7.64 (m, 2H; Ho), 7.25-7.15 (m, 2H), 7.15-7.06 (m, 4H), 6.75-6.66 (m, 2H), 6.63-6.57 (m, 2H) [HPh], 5.97 (dt, 3J = 15.8 Hz, 3J = 7.0 Hz, 1H, Hβ), 5.74 (d, 3J = 15.8 Hz, 1H, Hγ), 5.18-5.17 (m, 1H, H5), 3.34 (d, 3J = 7.0 Hz, 2H, Hα), 2.87 (dd, 2J = 13.4 Hz, 3J = 6.4 Hz 1H, 3-CH2), 2.602.50 (m, 1H, H4), 1.28 (dd, 2J = 13.4 Hz, 3J = 11.1 Hz, 1H, 3-CH2), 0.80 (d, 3J = 7.0 Hz, 3H, Me);

13

C{1H} NMR (С6D6): δ 208.6 (C=O), 162.5 (d, 1J = 246.1 Hz, C-F), 149.4 (C6), 140.3,

135.8, 133.6, 132.2, 129.0, 128.7, 128.6, 125.4, 125.2, 124.8 (13CPh), 124.8 (Cβ), 122.3 (Cγ), 115.3 (d, 2J = 21.6 Hz, CmPhF), 105.7 (C5), 87.6 (C2), 40.8 (Cα), 39.9 (C3), 25.4 (C4), 21.1 (Me). (E)-1-((2S*,4S*)-(4-Methyl-2,6-diphenyl-3,4-dihydro-2H-pyran-2-yl)-4-(thiophen-3-yl)but-3-en1-one (4f). Following general procedure, 4f was prepared from dihydropyran 2a (585 mg, 2 mmol) and acetylene 3f (216 mg, 2 mmol). 4f was isolated as a beige oil (593 mg, 74% yield). Anal. Calcd for C26H24O2S: C, 77.97; H, 6.04; S, 8.00. Found: C, 77.94; H, 6.00; S, 7.97. IR (film): ν 3059, 1955, 1889, 1806, 1718, 1653, 1105, 963; 1H NMR (С6D6): δ 7.76-7.70 (m, 2H, Ho), 7.69-7.64 (m, 2H, Ho), 7.25-7.15 (m, 2H), 7.13-7.06 (m, 3H), 7.05-6.99 (m, 1H) [HPh], 6.75 (d, 3J = 5.0 Hz, 1H, H5Thioph), 6.67 (dd, 3J = 5.0 Hz, 3J = 3.1 Hz, 1H, H4Thioph), 6.48 (d, 3J = 3.1 Hz, 1H, H2Thioph), 5.97 (dt, 3J = 16.0 Hz, 3J = 7.1 Hz, 1H, Hβ), 5.82 (d, 3J = 16.0 Hz, 1H, Hγ), 5.19-5.18 (m, 1H, H5), 3.32 (d, 3J = 7.1 Hz, 2H, Hα), 2.87 (dd, 2J = 13.8 Hz, 3J = 6.5 Hz, 1H, 3CH2), 2.58-2.50 (m, 1H, H4), 1.27 (dd, 2J = 13.8 Hz, 3J = 11.0 Hz, 1H, 3-CH2), 0.80 (d, 3J = 7.0 Hz, 3H, 4-Me); 13C{1H} NMR (С6D6): δ 208.7 (C=O), 149.6 (C6), 140.4, 140.1 (C3Thioph), 135.8, 129.0, 128.7, 128.6, 128.5, 125.4 (10CPh), 125.7 (Cβ), 125.2 (C2Thioph), 125.0 (C5Thioph), 122.2 (Cγ), 121.6 (C4Thioph), 105.7 (C5), 87.6 (C2), 40.7 (Cα), 40.0 (C3), 25.4 (C4), 21.1 (Me). (E)-1-((2S*,4S*)-(4-Methyl-2,6-di-p-tolyl-3,4-dihydro-2H-pyran-2-yl)-4-phenylbut-3-en-1-one (4g). Following general procedure, 4g was prepared from dihydropyran 2b (641 mg, 2 mmol) and acetylene 3a (204 mg, 2 mmol). 4g was isolated as a yellow oil (693 mg, 82% yield). Anal. Calcd for C30H30O2: C, 85.27; H, 7.16. Found: C, 85.29; H, 7.21. IR (film): ν 3029, 1945, 1908, 11 ACS Paragon Plus Environment


1798, 1717, 1652, 1099, 964; 1H NMR (С6D6): δ 7.73-7.71 (m, 2H, Ho), 7.65-7.53 (m, 2H, Ho), 7.05-6.98 (m, 2H), 6.97-6.80 (m, 7H) [HPh], 6.18 (dt, 3J = 15.8 Hz, 3J = 7.0 Hz, 1H, Hβ), 5.91 (d, 3

J = 15.8 Hz, 1H, Hγ), 5.20-5.18 (m, 1H, H5), 3.50-3.33 (m, 2H, Hα), 2.90 (dd, 2J = 13.5 Hz, 3J =

6.8 Hz, 1H, 3-CH2), 2.62-2.47 (m, 1H, H4), 2.08 (s, 3H, Me), 2.00 (s, 3H, Me), 1.31 (dd, 2J = 13.5 Hz, 3J = 11.1 Hz, 1H, 3-CH2), 0.81 (d, 3J = 6.9 Hz, 3H, 4-Me); 13C{1H} NMR (С6D6): δ 208.8 (C=O), 149.6 (C6), 138.2, 137.8, 137.6, 135.5, 133.4, 133.2, 129.7, 129.5, 129.3, 129.0, 128.6, 127.3, 125.2, 124.8 (18CPh), 126.5 (Cβ), 122.8 (Cγ), 104.9 (C5), 87.6 (C2), 40.8 (Cα), 40.1 (C3), 25.4 (C4), 21.2 (4-Me), 21.0 (2C, Me). (E)-4-([1,1'-Biphenyl]-4-yl)-1-((2S*,4S*)-(4-methyl-2,6-di-p-tolyl-3,4-dihydro-2H-pyran-2yl)but-3-en-1-one (4h). Following general procedure, 4h was prepared from dihydropyran 2b (641 mg, 2 mmol) and acetylene 3c (356 mg, 2 mmol). 4h was isolated as a yellow oil (788 mg, 79% yield). Anal. Calcd for C36H34O2: C, 86.71; H, 6.87. Found: C, 86.58; H, 6.92. IR (film): ν 3030, 1906, 1798, 1717, 1653, 1099, 965; 1H NMR (С6D6): δ 7.92-7.90 (m, 2H, Ho), 7.83-7.81 (m, 2H, Ho), 7.54-7.52 (m, 2H, Ho), 7.44-7.42 (m, 2H, Ho), 7.30-7.15 (m, 9H, HPh), 6.42 (dt, 2J = 15.4, 3J = 7.6 Hz, 1H, Hβ), 6.17 (d, 2J = 15.9 Hz, 1H, Hγ), 5.38 (m, 1H, H5), 3.72-3.60 (m, 2H, Hα), 3.14-3.09 (m, 1H, 3-CH2), 2.82-2.75 (m, 1H, H4), 2.28, 2.20 (s, 6H, 2Me), 1.57-1.50 (m, 1H, 3-CH2), 1.00 (d, 2J = 6.9 Hz, 3H, 4-Me); 13C{1H} NMR (С6D6): δ 208.5 (C=O), 149.3 (C6), 141.0, 140.0, 137.9, 137.5, 137.3, 136.3, 132.9, 132.8, 129.4, 129.2, 128.7, 127.0, 127.0, 126.9, 126.7, 124.6 (24C, Ph), 124.9 (Cβ), 122.6 (Cγ), 104.6 (C5), 87.3 (C2), 40.6 (Cα), 39.8 (C3), 25.2 (C4), 20.9, 20.9, 20.7 (3C, Me). (E)-4-(3-Methoxyphenyl)-1-((2S*,4S*)-(4-methyl-2,6-di-p-tolyl-3,4-dihydro-2H-pyran-2-yl)but3-en-1-one (4i). Following general procedure, 4i was prepared from dihydropyran 2b (641 mg, 2 mmol) and acetylene 3d (264 mg, 2 mmol). 4i was isolated as a yellow oil (751 mg, 83% yield). Anal. Calcd for C31H32O3: C, 82.27; H, 7.13. Found: C, 82.30; H, 7.16. IR (film): ν 3029, 1914, 1713, 1654, 1097, 965; 1H NMR (С6D6): δ 7.73-7.65 (m, 2H, Ho), 7.64-7.58 (m, 2H, Ho), 7.097.01 (m, 2H), 7.00-6.95 (m, 2H), 6.94-6.87 (m, 2H, H), 6.70-6.64 (m, 1H), 6.62-6.56 (m, 1H) [HPh], 6.25 (dt, 3J = 15.9 Hz, 3J = 6.9 Hz, 1H, Hβ), 5.96 (d, 3J = 15.9 Hz, 1H, Hγ), 5.19 (m, 1H, H5), 3.50-3.41 (m, 2H, Hα), 2.93 (dd, 2J = 13.3 Hz, 3J = 6.3 Hz, 1H, 3-CH2), 2.67-2.50 (m, 1H, H4), 2.09 (s, 3H, Me), 2.01 (s, 3H, Me), 1.35 (dd, 2J = 13.3 Hz, 3J = 11.3 Hz, 1H, 3-CH2), 0.81 (d, 3J = 6.8 Hz, 3H, 4-Me); 13C{1H} NMR (С6D6): δ 208.8 (C=O), 160.3 (C-OMe), 149.6 (C6), 139.0, 138.2, 137.8, 137.6, 133.6, 133.2, 129.7, 129.5, 125.2, 124.8 (14CPh), 125.2 (Cβ), 123.0 (Cγ), 119.2, 113.6, 111.7 (3CPh), 104.9 (C5), 87.6 (C2), 54.6 (OMe), 40.9 (Cα), 40.1 (C3), 25.5 (C4), 21.2 (4-Me), 20.9 (2C, Me).


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Page 13 of 21 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60


(E)-1-((2S*,4S*)-(4-Methyl-2,6-di-p-tolyl-3,4-dihydro-2H-pyran-2-yl)-4-(thiophen-3-yl)but-3en-1-one (4j). Following general procedure, 4j was prepared from dihydropyran 2b (641 mg, 2 mmol) and acetylene 3f (216 mg, 2 mmol). 4j was isolated as a yellow oil (660 mg, 77% yield). Anal. Calcd for C28H28O2S: C, 78.47; H, 6.59; S, 7.48. Found: C, 78.41; H, 6.61; S, 7.50. IR (film): ν 3028, 1909, 1717, 1656, 1094, 962; 1H NMR (С6D6): δ 7.71-7.66 (m, 2H, Ho), 7.637.58 (m, 2H, Ho), 7.04-7.00 (m, 2H), 6.98-6.93 (m, 2H) [HPh], 6.73 (d, 3J = 5.0 Hz, 1H, H5Thioph), 6.64 (dd, 3J = 5.0 Hz, 3J = 3.1 Hz, 1H, H4Thioph), 6.46 (d, 3J = 3.1 Hz, 1H, H2Thioph), 6.00 (dt, 3J = 15.9 Hz, 3J = 7.0 Hz, 1H, Hβ), 5.85 (d, 3J = 15.9 Hz, 1H, Hγ), 5.18 (m, 1H, H5), 3.42-3.35 (m, 2H, Hα), 2.90 (dd, 2J = 13.3 Hz, 3J = 6.7 Hz 1H, 3-CH2), 2.62-2.51 (m, 1H, H4), 2.08 (s, 3H, Me), 2.00 (s, 3H, Me), 1.35 (dd, 2J = 13.3 Hz, 3J = 11.3 Hz, 1H, 3-CH2), 0.80 (d, 3J = 6.9 Hz, 3H, 4-Me);

13

C{1H} NMR (С6D6): δ 208.8 (C=O), 149.6 (C6), 140.1 (C3Thioph), 138.2, 137.8,

137.7, 133.2, 129.7, 129.6, 125.2, 124.8 (10CPh), 125.6 (Cβ), 125.2 (C2Thioph), 125.0 (C5Thioph), 122.5 (Cγ), 121.6 (C4Thioph), 104.9 (C5), 87.6 (C2), 40.7 (Cα), 40.1 (C3), 25.5 (C4), 21.2 (4-Me), 20.1, 20.9 (Me). (E)-1-((2S*,4S*)-(2,6-Bis(4-fluorophenyl)-4-methyl-3,4-dihydro-2H-pyran-2-yl)-4-phenylbut-3en-1-one (4k). Following general procedure, 4k was prepared from dihydropyran 2c (763 mg, 2 mmol) and acetylene 3a (204 mg, 2 mmol). 4k was isolated as a yellow oil (1047 mg, 76% yield). Anal. Calcd for C28H24F2O2: C, 78.12; H, 5.62; F, 8.83. Found: C, 78.21; H, 5.59; F, 8.85. IR (film): ν 3041, 1895, 1719, 1655, 1096, 965; 1H NMR (С6D6): δ 7.50-7.39 (m, 4H), 7.12-6.90 (m, 5H), 6.89-6.75 (m, 4H) [HPh], 6.16 (dt, 3J = 15.9 Hz, 3J = 7.0 Hz, 1H, Hβ), 5.96 (d, 3J = 15.9 Hz, 1H, Hγ), 5.01-4.98 (m, 1H, H5), 3.27 (d, 3J = 7.0 Hz, 2H, Hα), 2.77 (dd, 2J = 13.6 Hz, 3J = 6.5 Hz 1H, 3-CH2), 2.52-2.43 (m, 1H, H4), 1.16 (dd, 2J = 13.6 Hz, 3J = 11.3 Hz, 1H, 3-CH2), 0.80 (d, 3

J = 6.9 Hz, 3H, Me); 13C{1H} NMR (С6D6): δ 208.3 (C=O), 163.3 (d, 1JCF = 247.6 Hz, C-F),

162.9 (d, 1JCF = 247.6 Hz, C-F), 148.5 (C6), 137.3, 135.8, 133.5, 129.0, 128.7, 128.6, 127.4, 125.4, 125.2, 124.8 (12CPh), 126.5 (Cβ), 122.2 (Cγ), 115.9, 115.8 (CPhF), 105.4 (C5), 87.2 (C2), 40.7 (Cα), 39.8.0 (C3), 25.3 (C4), 21.0 (Me). (E)-4-([1,1'-Biphenyl]-4-yl)-1-((2S*,4S*)-(2,6-di-tert-butyl-4-methyl-3,4-dihydro-2H-pyran-2yl)but-3-en-1-one (5l). Following general procedure, 4l was prepared from dihydropyran 2d (505 mg, 2 mmol) and acetylene 3c (356 mg, 2 mmol). 4l was isolated as a yellow oil (629 mg, 73% yield). Anal. Calcd for C30H38O2: C, 83.67; H, 8.89. Found: C, 83.47; H, 8.74. IR (film): ν 3031, 1903, 1709, 1072, 967; 1H NMR (С6D6): δ 7.42-7.40 (m, 2H), 7.39-7.35 (m, 2H), 7.32-7.27 (m, 2H), 7.21-7.15 (m, 2H), 7.11-7.05 (m, 1H) [HPh], 6.59 (ddd, 3J = 16.1 Hz, 3J = 7.4 Hz, 3J = 6.4 Hz, 1H, Hβ), 5.39 (d, 3J = 16.1 Hz, 1H, Hγ), 4.39-4.35 (m, 1H, H5), 3.76 (dd, 2J = 19.3 Hz, 3J = 7.4 Hz, 1H, Hα), 3.34 (dd, 2J = 19.3 Hz, 3J = 6.4 Hz, 1H, Hα), 2.40 (dd, 2J = 12.5 Hz, 3J = 5.1 Hz, 13 ACS Paragon Plus Environment


1H, 3-CH2), 2.05-1.95 (m, 1H, H4), 1.15 (s, 9H, But), 1.00 (s, 10H, 3-CH2, But), 0.79 (d, 3J = 6.7 Hz, 3H, Me);

13

C{1H} NMR (С6D6): δ 213.3 (C=O), 159.4 (C6), 141.3, 140.5, 136.7, 132.7,

129.1, 129.0, 128.9, 128.1, 128.6, 127.9, 127.3 (12CPh), 127.1 (Cβ), 123.5 (Cγ), 99.4 (C5), 90.2 (C2), 45.0 (C-Me3), 38.3 (Cα), 35.4 (C3), 33.3, 28.7, 25.6 (3C, But), 24.1 (C4), 22.0 (Me). 2,6-Di[1,1'-biphenyl]-4-yl-4-methyl-3,4-dihydro-2H-pyran (6a). Following general procedure, 6a was prepared from dihydropyran 2e (889 mg, 2 mmol) and acetylene 3a (204 mg, 2 mmol). 6a was isolated as a mixture of two diastereomers in a 2 : 1 molar ratio; yield 636 mg (79%); white solid; mp 108-110 oС. Anal. Calcd for C30H26O: C, 89.51; H, 6.51. Found: C, 89.75; H, 6.46. IR (film): ν 3032, 1949, 1913, 1801, 1647, 1109. (2S*,4R*)-2,6-Di([1,1'-biphenyl]-4-yl)-4methyl-3,4-dihydro-2H-pyran (major isomer). 1H NMR (СDCl3): δ 7.72-7.69 (m, 2H, Ho), 7.627.30 (m, 16H, HPh), 5.48 (d, 3J = 4.4 Hz, 1H, H5), 5.11 (d, 3J = 9.8 Hz, 1H, H2), 2.47-2.43 (m, 1H, H4), 2.19-2.14 (m, 1H, H3), 1.87-1.84 (m, 1H, H3), 1.20 (d, 3J = 7.1 Hz, 3H, Me); 13C{1H} NMR (СDCl3): δ 150.5 (C6), 141.4 (Ci), 141.0-140.5 (4CPh), 135.0 (Ci), 128.9-126.9 (14CPh), 126.4, 125.1 (2Co), 103.8 (C5), 74.1 (C2), 37.3 (C3), 25.5 (C4), 22.8 (Me). (2S*,4S*)-2,6Di([1,1'-biphenyl]-4-yl)-4-methyl-3,4-dihydro-2H-pyran (minor isomer). 1H NMR (СDCl3): δ 7.71-7.69 (m, 2H, Ho), 7.62-7.30 (m, 16H, HPh), 5.35 (s, 1H, H5), 5.08 (d, 3J = 11.7 Hz, 1H, H2), 2.78-2.75 (m, 1H, H4), 2.21-2.19 (m, 1H, H3), 1.65-1.62 (m, 1H, H3), 1.14 (d, 3J = 7.0 Hz, 3H, Me);

13

C{1H} NMR (СDCl3): δ 150.8 (C6), 141.3 (Ci), 141.0-140.5 (4CPh), 134.9 (Ci), 128.9-

126.9 (14CPh), 126.6 (2Co), 125.1 (2Co), 104.1 (C5), 78.1 (C2), 40.0 (C3), 28.5 (C4), 21.6 (Me). 4-Methyl-2,6-di(2-naphthyl)-3,4-dihydro-2H-pyran (6b). Following general procedure, 6b was prepared from dihydropyran 2f (785 mg, 2 mmol) and acetylene 3a (204 mg, 2 mmol). 6b was isolated as a mixture of two diastereomers in a 2 : 1 molar ratio; yield 568 mg (81%); white solid; mp 81-83 oС. Anal. Calcd for C26H22O: C, 89.11; H, 6.33. Found: C, 89.21; H, 6.28. IR (film): ν 3055, 1919, 1644, 1071. (2S*,4R*)-4-Methyl-2,6-di(naphthalen-2-yl)-3,4-dihydro-2Hpyran (major isomer). 1H NMR (СDCl3): δ 8.15 (s, 1H), 7.90 (s, 1H), 7.74-7.76 (m, 1H), 7.557.54 (m, 1H), 7.94-7.39 (m, 10H) [HNaphth], 5.58 (d, 3J = 4.2 Hz, 1H, H5), 5.27 (d, 3J = 9.8 Hz, 1H, H2), 2.47-2.44 (m, 1H, H4), 2.20-2.18 (m, 1H, H3), 1.91-1.89 (m, 1H, H3), 1.22 (d, 3J = 7.1 Hz, 3H, Me); 13C{1H} NMR (СDCl3): δ 150.7 (C6), 139.7 (C2Naphth), 133.4-133.1, 128.4-125.8 (14CNaphth), 132.9 (C2Naphth), 124.6 (C1Naphth), 124.2 (C3Naphth), 123.4 (C1Naphth), 122.8 (C3Naphth), 104.5 (C5), 74.5 (C2), 37.3 (C3), 25.6 (C4), 22.8 (Me). (2S*,4S*)-4-Methyl-2,6-di(naphthalen-2yl)-3,4-dihydro-2H-pyran (minor isomer). 1H NMR (СDCl3): δ 8.11 (s, 1H), 7.94 (s, 1H), 7.727.70 (m, 1H), 7.59-7.58 (m, 1H), 7.94-7.39 (m, 10H) [HNaphth], 5.46 (s, 1H, H5), 5.21 (d, 3J = 11.1 Hz, 1H, H2), 2.79-2.78 (m, 1H, H4), 2.25-2.21 (m, 1H, H3), 1.73 (m, 1H, H3), 1.17 (d, 3J = 6.9 Hz, 3H, Me);

13

C{1H} NMR (СDCl3): δ 151.0 (C6), 139.6, 133.0 (2C2Naphth), 128.4-124.8 14 ACS Paragon Plus Environment

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(14CNaphth), 124.9 (C1Naphth), 124.4 (C3Naphth), 123.5 (C1Naphth), 122.8 (C3Naphth), 104.7 (C5), 78.4 (C2), 39.9 (C3), 28.6 (C4), 21.5 (Me). General procedure for the Rearrangement of Dihydropyrans 4 to DOBCOs 5. A mixture of dihydropyran 4 (1 mmol), NH4Cl (1.5 mmol, 80 mg) and H2O (1.5 mL) was reflux in MeCN (7.5 mL) for 8 h. The reaction mixture, after cooling (rt), was diluted with Et2O and dried (K2CO3). Et2O and MeCN was evaporated in vacuum and the residue was purified by column chromatography (basic Al2O3, eluent hexane). (1R*,3R*,5S*,Z)-3-Methyl-1,5-diphenyl-7-((E)-3-phenylallylidene)-6,8dioxabicyclo[3.2.1]octane (5a). Following general procedure, 5a was prepared from dihydropyran 4a (395 mg, 1 mmol). 5a was isolated as a colorless oil (281 g, 71% yield). Anal. Calcd for C28H26O2: C, 85.25; H, 6.64. Found: C, 85.31; H, 6.61. IR (film): ν 3033, 1953, 1895, 1799, 1667, 1610, 1565, 1506, 1087, 945; 1H NMR (CDCl3): δ 7.77-7.74 (m, 2H, Ho’), 7.647.63 (m, 2H, Ho), 7.48-7.35 (m, 10H, HPh), 7.17-7.13 (m, 1H, Hp”), 7.10 (dd, 3J = 15.9 Hz, 3J = 11.0 Hz, 1H, Hβ), 6.28 (d, 3J = 15.9 Hz, 1H, Hγ), 4.82 (d, 3J = 11.0 Hz, 1H, Hα), 2.42 (m, 3H, H2eq, H3, H4eq), 1.82 (dd, 2J = 11.8 Hz, 3J = 11.3 Hz, 1H, H2ax), 1.74 (dd, 2J = 14.4, 3J = 12.1 Hz, 1H, H4ax), 1.12 (d, 3J = 5.9 Hz, 3H, Me);

13

C{1H} NMR (CDCl3): δ 158.1 (C7), 139.4, 139.3,

138.1 (Ci, Ci’, Ci”), 128.9 (Cγ), 128.4, 128.3, 128.3, 127.9, 127.9, 126.6, 126.2, 125.90, 125.5 (15CPh), 123.5 (Cβ), 110.8 (C5), 96.5 (Cα), 85.8 (C1), 42.0 (C4), 41.0 (C2), 25.3 (C3), 21.3 (3-Me). (1R*,3R*,5S*,Z)-3-Methyl-1,5-diphenyl-7-((E)-3-(p-tolyl)allylidene)-6,8dioxabicyclo[3.2.1]octane (5b). Following general procedure, 5b was prepared from dihydropyran 4b (409 mg, 1 mmol). 5b was isolated as a white oil (278 mg, 68% yield). Anal. Calcd for C29H28O2: C, 85.26; H, 6.91. Found: C, 85.48; H, 6.78. IR (film): ν 3033, 1953, 1895, 1798, 1667, 1610, 1565, 1506, 1087, 945; 1H NMR (CDCl3): δ 7.75-7.73 (m, 2H, Ho’), 7.637.60 (m, 2H, Ho), 7.47-7.36 (m, 6H, HPh), 7.26-7.24 (m, 2H, Ho”), 7.08-7.06 (m, 2H, Hm”), 7.03 (dd, 3J = 15.7 Hz, 3J = 10.8 Hz, 1H, Hβ), 6.24 (d, 3J = 15.7 Hz, 1H, Hγ), 4.80 (d, 3J = 10.8 Hz, 1H, Hα), 2.45-2.36 (m, 3H, H2eq, H3, H4eq), 2.31 (s, 3H, Me), 1.81 (dd, 2J = 11.5 Hz, 3J = 11.3 Hz, 1H, H2ax), 1.73 (dd, 2J = 14.4 Hz, 3J = 12.0 Hz, 1H, H4ax), 1.11 (d, 3J = 5.9 Hz, 3H, 3Me);

13

C{1H} NMR (CDCl3): δ 157.8 (C7), 139.5, 139.4, 136.5, 135.4, 129.2, 129.0, 128.4,

128.4 (11CPh), 128.3 (Cγ), 128.0 (Cp’), 126.3, 126.0, 125.6 (6CPh), 122.4 (Cβ), 109.8 (C5), 96.70 (Cα), 85.9 (C1), 42.1 (C4), 40.8 (C2), 25.5 (C3), 21.4 (3-Me), 21.3 (Me). (1R*,3R*,5S*,Z)-7-((E)-3-([1,1'-Biphenyl]-4-yl)allylidene)-3-methyl-1,5-diphenyl-6,8dioxabicyclo[3.2.1]octane (5c). Following general procedure, 5c was prepared from dihydropyran 4c (470 mg, 1 mmol). 5c was isolated as a yellow oil (310 mg, 66% yield). Anal. Calcd for C34H30O2: C, 86.77; H, 6.43. Found: C, 86.88; H, 6.38. IR (film): ν 3032, 1953, 1894, 1807, 1666, 1602, 1488, 1087, 945; 1H NMR (CDCl3): δ 7.78-7.75 (m, 2H, Ho), 7.63-7.58 (m, 15 ACS Paragon Plus Environment


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6H), 7.46-7.36 (m, 11H) [HPh], 7.14 (dd, 3J = 15.8 Hz, 3J = 10.9 Hz, 1H, Hβ), 6.31 (d, 3J = 15.8 Hz, 1H, Hγ), 4.85 (d, 3J = 10.9 Hz, 1H, Hα), 2.46-2.41 (m, 3H; H2eq, H3, H4eq), 1.83 (dd, 2J = 11.9 Hz, 3J =11.2 Hz, 1H, H2ax), 1.75 (dd, 2J = 14.3 Hz, 3J = 12.0 Hz, 1H, H4ax), 1.13 (d, 3J = 6.0 Hz, 3H, 3-Me); 13C{1H} NMR (CDCl3): δ 158.3 (C7), 140.9, 139.4, 139.3, 137.3, 129.1, 128.8, 128.5 (8CPh), 128.45 (Cγ), 128.40, 127.46, 127.19, 127.17, 126.89, 126.43, 126.29, 125.57 (16CPh), 123.5 (Cβ), 109.9 (C5), 96.7 (Cα), 86.0 (C1), 42.1 (C4), 40.8 (C2), 25.5 (C3), 21.4 (3-Me). (1R*,3R*,5S*,Z)-7-((E)-3-(3-Methoxyphenyl)allylidene)-3-methyl-1,5-diphenyl-6,8-dioxabicyclo[3.2.1]octane (5d). Following general procedure, 5d was prepared from dihydropyran 4d (425 mg, 1 mmol). 5d was isolated as colorless oil (281 mg, 66% yield). Anal. Calcd for C29H28O3: C, 82.05; H, 6.65. Found: C, 81.98; H, 6.68. IR (film): ν 3033, 1666, 1596, 1488, 1088, 949; 1H NMR (CDCl3): δ 7.76-7.73 (m, 2H, Ho’), 7.63-7.60 (m, 2H, Ho), 7.47-7.37 (m, 6H, HPh), 7.19-7.14 (m, 1H, Hm”), 7.07 (dd, 3J = 15.8 Hz, 3J = 11.0 Hz, 1H, Hβ), 6.95 (d, 3J = 7.7 Hz, 1H, Ho”), 6.89 (s, 1H, Ho”), 6.72 (d, 3J = 8.3 Hz, 1H, Hp”), 6.24 (d, 3J = 15.8 Hz, 1H, Hγ), 4.80 (d, 3J = 11.0 Hz, 1H, Hα), 2.45-2.37 (m, 3H, H2eq, H3, H4eq), 1.81 (dd, 2J = 10.0 Hz, 3J = 9.8 Hz, 1H, H2ax), 1.73 (dd, 2J = 14.3 Hz, 3J = 12.8 Hz, 1H, H4ax), 1.11 (d, 3J = 5.9 Hz, 3H, 3Me); 13C{1H} NMR (CDCl3): δ 159.8 (C-OMe), 158.3 (C7), 139.7 (Ci”), 139.4 (Ci, Ci’), 129.4 (Cp’), 129.1 (Cp), 128.4 (Cm, Cm’), 128.1 (Cγ), 127.9 (Cm”), 126.3 (Co), 125.5 (Co’), 123.7 (Cβ), 118.9 (Co”), 112.4 (Cp”), 111.2 (Co”), 109.9 (C5), 96.5 (Cα), 85.9 (C1), 55.3 (OMe), 42.0 (C4), 40.8 (C2), 25.4 (C3), 21.4 (3-Me). (1R*,3R*,5S*,Z)-7-((E)-3-(4-Fluorophenyl)allylidene)-3-methyl-1,5-diphenyl-6,8-dioxabicyclo[3.2.1]octane (5e). Following general procedure, 5e was prepared from dihydropyran 4e (413 mg, 1 mmol). 5e was isolated as a yellow oil (231 mg, 56% yield). Anal. Calcd for C28H25FO2: C, 81.53; H, 6.11; F, 4.61. Found: C, 81.49; H, 6.05; F, 4.63. IR (film): ν 3040, 1954, 1888, 1814, 1667, 1601, 1505, 1089, 945; 1H NMR (CDCl3): δ 7.78-7.75 (m, 2H, Ho), 7.65-7.62 (m, 2H, Ho), 7.47-7.36 (m, 6H), 7.32-7.31 (m, 2H) [HPh], 7.03 (dd, 3J = 15.8 Hz, 3J = 11.0 Hz, 1H, Hβ), 6.97 (m, 2H, HPhF), 6.24 (d, 3J = 15.8 Hz, 1H, Hγ), 4.82 (d, 3J = 11.0 Hz, 1H, Hα), 2.43 (m, 3H; H2eq, H3, H4eq), 1.84 (dd, 2J = 12.0 Hz, 3J = 11.8 Hz, 1H, H2ax), 1.76 (dd, 2J = 15.4 Hz, 3J = 12.8 Hz, 1H, H4ax), 1.13 (d, 3J = 5.6 Hz, 3H, 3-Me);

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C{1H} NMR (CDCl3): δ

162.3 (d, 1JCF = 246.7 Hz, C-F), 158.2 (C7), 139.4, 139.3, (Ci, Ci’), 134.4 (CPhF), 129.0 (Cγ), 128.4, 127.3, 126.7, 126.3, 125.5 (2CPhF, 10CPh), 123.1 (Cβ), 115.4 (d, 3JCF = 21.0 Hz, 2CPhF), 109.9 (C5), 96.4 (Cα), 85.9 (C1), 42.0 (C4), 40.7 (C2), 25.4 (C3), 21.4 (3-Me). (1R*,3R*,5S*,Z)-3-Methyl-1,5-diphenyl-7-((E)-3-(thiophen-3-yl)allylidene)-6,8-dioxabicyclo[3.2.1]octane (5f). Following general procedure, 5f was prepared from dihydropyran 4f (401 mg, 1 mmol). 5f was isolated as a yellow oil (213 mg, 53% yield). Anal. Calcd for C26H24O2S: C, 77.97; H, 6.04; S, 8.01. Found: C, 77.89; H, 5.99; S, 7.95. IR (film): ν 3037, 16 ACS Paragon Plus Environment

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1955, 1887, 1810, 1668, 1607, 1598, 1088, 952; 1H NMR (CDCl3): δ 7.80-7.77 (m, 2H, Ho), 7.68-7.65 (m, 2H, Ho), 7.52-7.43 (m, 7H, HPh, HThioph), 7.30-7.27 (m, 1H), 7.09-7.06 (m, 1H) [HThioph], 6.97 (dd, 3J = 15.7 Hz, 3J = 10.9 Hz, 1H, Hβ), 6.34 (d, 3J = 15.7 Hz, 1H, Hγ), 4.81 (d, 3J = 10.9 Hz, 1H, Hα), 2.50-2.41 (m, 3H, H2eq, H3, H4eq), 1.81 (dd, 2J = 11.7 Hz, 3J = 10.5 Hz, 1H, H2ax), 1.73 (dd, 2J = 14.6 Hz, 3J = 12.3 Hz, 1H, H4ax), 1.16 (d, 3J = 5.9 Hz, 3H, 3-Me); 13C{1H} NMR (CDCl3): δ 157.8 (C7), 140.9 (C3Thioph), 139.5 (Ci”), 139.4 (Ci’), 129.0 (Cp’), 128.4, 128.4 (4C, Cm, Cm’), 128.3 (Cp), 126.3 (2C, Co), 125.7 (C5Thioph), 125.5 (2C, Co’), 125.1 (C4Thioph), 123.4 (Cβ), 122.3 (Cγ), 120.4 (C2Thioph), 109.8 (C5), 96.4 (Cα), 85.8 (C1), 42.0 (C4), 40.8 (C2), 25.4 (C3), 21.4 (3-Me). (1R*,3R*,5S*,Z)-3-Methyl-7-((E)-3-phenylallylidene)-1,5-di-p-tolyl-6,8dioxabicyclo[3.2.1]octane (5g). Following general procedure, 5g was prepared from dihydropyran 4g (423 mg, 1 mmol). 5g was isolated as a white solid (317 mg, 75% yield); mp 79-81 oС. Anal. Calcd for C30H30O2: C, 85.27; H, 7.16. Found: C, 85.33; H, 7.11. IR (film): ν 3028, 1907, 1803, 1667, 1616, 1598, 1513, 1072, 945; 1H NMR (C6D6): δ 7.86-7.83 (m, 2H, Ho’), 7.67-7.64 (m, 2H, Ho), 7.59 (dd, 3J = 16.1 Hz, 3J = 10.8 Hz, 1H, Hβ), 7.36-7.34 (m, 2H, Ho”), 7.19-7.14, (m, 6H, Hm, Hm’, Hm”), 7.08-7.04, (m, 1H, Hp”), 6.30 (d, 3J = 16.1 Hz, 1H, Hγ), 5.10 (d, 3J = 10.8 Hz, 1H, Hα), 2.40-2.36 (m, 1H, H3), 2.28-2.24 (m, 2H, H2eq, H4eq), 2.23 (s, 3H, Me), 2.21 (s, 3H, Me), 1.75 (dd, 2J = 12.3 Hz, 3J = 12.2 Hz, 1H, H2ax), 1.65 (dd, 2J = 13.3 Hz, 3J = 11.4 Hz, 1H, H4ax), 0.91 (d, 3J = 6.6 Hz, 3H, 3-Me);

13

C{1H} NMR (C6D6): δ 158.9

(C7), 138.7 (Cp’), 138.7 (Ci”), 138.0 (Cp), 137.35 (Ci’), 137.3 (Ci), 129.2 (4C, Cm, Cm’), 128.8 (2C, Cm”), 128.4 (Cγ), 126.8 (3C, Co, Cp”), 126.3 (2C, Co”), 126.0 (2C, Co’), 123.8 (Cβ), 110.2 (C5), 97.2 (Cα), 86.1 (C1), 42.4 (C4), 40.8 (C2), 25.6 (C3), 21.4 (3-Me), 21.1, 21.0 (2C, Me). (1R*,3R*,5S*,Z)-7-((E)-3-([1,1'-Biphenyl]-4-yl)allylidene)-3-methyl-1,5-di-p-tolyl-6,8dioxabicyclo[3.2.1]octane (5h). Following general procedure, 5h was prepared from dihydropyran 4h (499 mg, 1 mmol). 5h was isolated as a white solid (354 mg, 71% yield); mp 88-90 oС. Anal. Calcd for C36H34O2: C, 86.71; H, 6.87. Found: C, 86.63; H, 6.81. IR (film): ν 3038, 1906, 1800, 1665, 1604, 1515, 1074, 943; 1H NMR (CDCl3): δ 7.68-7.65 (m, 2H, Ho’), 7.62-7.59 (m, 2H, Ho), 7.54-7.48 (m, 4H), 7.37-7.30 (m, 9H) [HPh], 7.15 (dd, 3J = 15.8 Hz, 3J = 11.0 Hz, 1H, Hβ), 6.30 (d, 3J = 15.8 Hz, 1H, Hγ), 4.84 (d, 3J = 11.0 Hz, 1H, Hα), 2.43 (s, 3H, Me), 2.40 (s, 3H, Me), 2.39 (m, 3H, H2eq, H3, H4eq), 1.81 (dd, 2J = 12.1 Hz, 3J = 10.1 Hz, 1H, H2ax), 1.74 (dd, 2J = 13.2 Hz, 3J = 11.1 Hz, 1H, H4ax), 1.12 (d, 3J = 5.9 Hz, 3H, 3-Me); 13C{1H} NMR (CDCl3): δ 158.7 (C7), 140.9, 139.2, 138.9, 138.1, 137.4, 136.6, 129.1, 129.0 (10CPh), 128.8 (Cγ), 127.2, 126.9, 126.4, 126.3, 125.5 (14CPh), 123.7 (Cβ), 109.9 (C5), 96.4 (Cα), 85.9 (C1), 41.8 (C4), 40.7 (C2), 25.4 (C3), 21.5 (3-Me), 21.4, 21.3 (2C, Me). 17 ACS Paragon Plus Environment


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(1R*,3R*,5S*,Z)-7-((E)-3-(3-Methoxyphenyl)allylidene)-3-methyl-1,5-di-p-tolyl-6,8dioxabicyclo[3.2.1]octane (5i). Following general procedure, 5i was prepared from dihydropyran 4i (453 mg, 1 mmol). 5i was isolated as a yellow oil (285 mg, 63% yield). Anal. Calcd for C31H32O3: C, 82.27; H, 7.13. Found: C, 82.33; H, 7.09. IR (film): ν 3030, 1909, 1796, 1668, 1597, 1578, 1515, 1079, 951; 1H NMR (CDCl3): δ 7.60-7.57 (m, 2H. Ho’), 7.46-7.43 (m, 2H, Ho), 7.25-7.17 (m, 4H, HPh), 7.16-7.13 (m, 1H, Hm”), 7.04 (dd, 3J = 15.8 Hz, 3J = 11.0 Hz, 1H, Hβ), 6.91 (d, 3J = 7.5 Hz, 1H, Ho”), 6.85 (s, 1H, Ho”), 6.67-6.65 (m, 1H, Hp”), 6.19 (d, 3J = 15.8 Hz, 1H, Hγ), 4.75 (d, 3J = 11.0 Hz, 1H, Hα), 3.77 (s, 3H, OMe), 2.40-2.33 (m, 3H, H2eq, H3, H4eq), 2.38 (s, 3H, Me), 2.35 (s, 3H, Me), 1.76 (dd, 2J = 13.7 Hz, 3J = 12.2 Hz, 1H, H2ax), 1.67 (dd, 2J = 14.4 Hz, 3J = 12.6 Hz, 1H, H4ax), 1.07 (d, 3J = 5.8 Hz, 3H, 3-Me);

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C{1H} NMR

(CDCl3): δ 159.84 (C-OMe), 158.7 (C7), 139.8 (Ci”), 138.9 (Ci’), 138.1 (Ci), 136.50 (Cp), 129.40 (Cp’), 129.1, 129.0, (4C, Cm, Cm’), 127.6 (Cγ), 127.7 (Cm”), 126.3 (2C, Co), 125.5 (2C, Co’), 123.8 (Cβ), 118.9 (Cp”), 112.4, 111.1 (2C, Co”), 109.9 (C5), 96.3 (Cα), 85.9 (C1), 55.3 (MeO), 41.8 (C4), 40.7 (C2), 25.4 (C3), 21.4 (3-Me), 21.4, 21.2 (2C, Me). (1R*,3R*,5S*,Z)-3-Methyl-7-((E)-3-(thiophen-3-yl)allylidene)-1,5-di-p-tolyl-6,8dioxabicyclo[3.2.1]octane (5j). Following general procedure, 5j was prepared from dihydropyran 4j (429 mg, 1 mmol). 5j was isolated as a yellow oil (296 mg, 69% yield). Anal. Calcd for C28H28O2S: C, 78.47; H, 6.59; S, 7.48. Found: C, 78.41; H, 6.61; S, 7.50. IR (film): ν 3033, 1909, 1802, 1742, 1668, 1618, 1515, 1075, 955; 1H NMR (CDCl3): δ 7.55-7.52 (m, 2H, Ho’), 7.39-7.36 (m, 2H, Ho), 7.19-7.14 (m, 3H, HPh, HThioph), 7.12-7.09 (m, 3H, HPh, HThioph), 6.90 (s, 1H, HThioph), 6.79 (dd, 3J = 15.8 Hz, 3J = 11.0 Hz, 1H, Hβ), 6.17 (d, 3J = 15.8 Hz, 1H, Hγ), 4.63 (d, 3J = 11.0 Hz, 1H, Hα), 2.30 (s, 3H, Me), 2.27 (s, 3H, Me), 2.26-2.21 (m, 3H, H2eq, H3, H4eq), 1.67 (dd, 2J = 11.7 Hz, 3J = 10.5 Hz, 1H, H2ax), 1.60 (dd, 2J = 14.6 Hz, 3J = 12.3 Hz, 1H, H4ax), 0.99 (d, 3J = 5.9 Hz, 3H, 3-Me);

13

C{1H} NMR (CDCl3): δ 158.1 (C7), 140.9

(C3Thioph), 138.8 (Ci’), 137.9 (Ci), 136.5 (Cp, Cp’), 129.0, 128.9 (4C, Cm, Cm’), 126.2 (2C, Co), 125.6 (C5Thioph), 125.4 (2C, Co’), 125.0 (C4Thioph), 123.5 (Cβ), 121.9 (Cγ), 120.2 (C2Thioph), 109.6 (C5), 96.0 (Cα), 85.7 (C1), 42.8 (C4), 40.7 (C2), 25.3 (C3), 21.3 (3-Me), 21.3, 21.1 (2C, Me). (1R*,3R*,5S*,Z)-1,5-Bis(4-fluorophenyl)-3-methyl-7-((E)-3-phenylallylidene)-6,8dioxabicyclo[3.2.1]octane (5k). Following general procedure, 5k was prepared from dihydropyran 4k (431 mg, 1 mmol). 5k was isolated as a white solid (258 mg, 60% yield); mp 64-66 oС. Anal. Calcd for C28H24F2O2: C, 78.12; H, 5.62; F, 8.83. Found: C, 78.21; H, 5.59; F, 8.85. IR (film): ν 3030, 1894, 1668, 1604, 1515, 1071, 951; 1H NMR (CDCl3): δ 7.72-7.69 (m, 2H, Ho’), 7.59-7.55 (m, 2H, Ho), 7.37-7.32 (m, 2H, Ho”), 7.17-7.19, (m, 7H, HPh), 7.07 (dd, 3J = 15.8 Hz, 3J = 11.3 Hz, 1H, Hβ), 6.29 (d, 3J = 15.8 Hz, 1H, Hγ), 4.77 (d, 3J = 11.3 Hz, 1H, Hα), 2.38-2.33 (m, 3H, H2eq,H3, H4eq), 1.80 (dd, 2J = 13.2 Hz, 3J = 9.9 Hz, 1H, H2ax), 1.71 (dd, 2J = 18 ACS Paragon Plus Environment

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13.4 Hz, 3J = 11.1 Hz, 1H, H4ax), 1.12 (d, 3J = 5.9 Hz, 3H, Me); 13C{1H} NMR (CDCl3): δ 163.2 (d, 1JCF = 247.5 Hz, Cp’), 162.8 (d, 1JCF = 247.1 Hz, Cp), 157.8 (C7), 138.0 (Ci”), 135.2 (d, 4JCF = 3.3 Hz, Ci), 135.1 (d, 4JCF = 3.3 Hz, Ci’), 128.6 (3C, Cγ, Cm”), 128.3 (d, 3JCF = 8.3 Hz, Co), 127.6 (d, 3JCF = 8.3 Hz, Co’), 126.9 (Cp”), 126.1 (2C, Co”), 123.0 (Cβ), 115.4 (d, 2JCF = 21.6 Hz, Cm’), 115.3 (d, 2JCF = 21.6 Hz, Cm), 109.5 (C5), 96.9 (Cα), 85.6 (C1), 41.9 (C4), 40.7 (C2), 25.4 (C3), 21.4 (3-Me). (1R*,3R*,5S*,Z)-7-((E)-3-([1,1'-Biphenyl]-4-yl)allylidene)-1,5-di-tert-butyl-3-methyl-6,8dioxabicyclo[3.2.1]octane (5l). Following general procedure, 5l was prepared from dihydropyran 4l (430 mg, 1 mmol). 5l was isolated as a white solid (245 mg, 57% yield); mp 57-58 oС. Anal. Calcd for C30H38O2: C, 83.67; H, 8.89. Found: C, 83.51%; H, 8.81. IR (film): ν 3029, 1902, 1796, 1655, 1602, 1515, 1085, 965; 1H NMR (CDCl3): δ 7.59-7.56 (m, 2H), 7.53-7.50 (m, 2H), 7.49-7.43 (m, 4H), 7.31-7.28 (m, 1H) [HPh], 7.16 (dd, 3J = 15.9 Hz, 3J = 10.6 Hz, 1H, Hβ), 6.36 (d, 3J = 15.9 Hz, 1H, Hγ), 5.23 (d, 3J = 10.6 Hz, 1H, Hα), 1.94-1.90 (m, 2H, H2eq, H4eq), 1.73-1.69 (m, 1H, H3), 1.34 (dd, 2J = 11.9 Hz, 3J = 11.3 Hz, 1H, H2ax), 1.23 (dd, 2J = 12.9 Hz, 3J = 11.0 Hz, 1H, H4ax), 1.09 (s, 9H, But), 1.05 (s, 9H, But), 0.93 (d, 3J = 6.4 Hz, 3H, 3-Me); 13C{1H} NMR (CDCl3): δ 157.9 (C7), 141.0, 139.0, 137.8 (3C, Ci, Ci’, Cp), 128.8 (Cγ), 127.2, 127.1 (4C, Cm, Cm’), 127.0 (Cp’), 126.9, 126.3 (4C, Co, Co’), 124.7 (Cβ), 112.7 (C5), 95.6 (Cα), 89.5 (C1), 36.9 (C4), 36.6 (C-But), 35.6 (C2), 35.1 (C-But), 26.1 (3C, But), 25.3 (C3), 25.1(3C, But), 21.9 (3-Me).

ASSOCIATED CONTENT

AUTHOR INFORMATION Corresponding Author *E-mail: [email protected] ORCID Boris A. Trofimov: 0000-0002-0430-3215 Notes The authors declare no competing financial interest. ACKNOWLEDGMENT We acknowledge the Baikal Analytical Center for collective use of the Siberian Branch of the Russian Academy of Sciences for the equipment. Supporting Information The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.joc. Copies of 1H and 13C NMR spectra of all compounds (PDF). REFERENCES 19 ACS Paragon Plus Environment


(1) (a) Francke, W.; Schroeder, W. Bicyclic Acetals in Systems of Chemical Communication. Curr. Org. Chem. 1999, 3, 407-433. (b) Yus, M.; Ramon, D. J.; Prieto, O. (-)-Frontalin: Synthesis using the Catalytic Enantioselective Addition of Dimethylzinc to a Ketone. Eur. J. Org. Chem. 2003, 2745-2748. (2) (a) Vanderwel, D.; Oehlschlager, A. C. Mechanism of Brevicomin Biosynthesis from (Z)-6Nonen-2-one in a Bark Beetle. J. Am. Chem. Soc. 1992, 114, 5081-5086. (b) Mori, K. Pheromone Synthesis. In Topics in Current Chemistry, Vol. 239; Pheromone and Other Semiochemicals I; Schulz, S., Ed.; Springer: Heidelberg, 2004; pp 1-50. (3) Berens, U.; Scharf, H.-D. The First Stereoselective Synthesis of Racemic β-Multistriatin: A Pheromone Component of the European Elm Bark Beetle Scolytus multistriatus (Marsh.). J. Org. Chem. 1995, 60, 5127-5134. (4) (a) Rasmussen, L. E. L.; Greenwood, D. R. Frontalin: a Chemical Message of Musth in Asian Elephants (Elephas Maximus). Chem. Senses 2003, 28, 433-446. (b) Greenwood, D. R.; Comeskey, D.; Hunt, M. B.; Rasmussen, L. E. L. Chemical Communication: Chirality in Elephant Pheromones. Nature 2005, 438, 1097-1098. (5) Liu, J.-H.; Jin, Y.; Long, Y.-Q. Synthesis of the C5–C30 Fragment of Cyclodidemniserinol Trisulfate via I2-Mediated Deprotection and Ring Closure Tandem Reaction. Tetrahedron 2010, 66, 1267-1273. (6) (a) Kiyota, H.; Dixon, D. J.; Luscombe, C. K.; Hettstedt, S.; Ley, S. V. Synthesis, Structure Revision, and Absolute Configuration of (+)-Didemniserinolipid B, a Serinol Marine Natural Product from a Tunicate Didemnum sp. Org. Lett. 2002, 4, 3223-3226. (b) Ren, J.; Wang, J.; Tong, R. Asymmetric Total Synthesis of (+)-Attenol B. Org. Lett. 2015, 17, 744-747. (c) Czubatka-Bienkowska, A.; Sarnik, J.; Macieja, A.; Galita, G.; Witczak, Z. J.; Poplawski, T. Thio-Functionalized Carbohydrate Thiosemicarbazones and Evaluation of Their Anticancer Activity. Bioorg. Med. Chem. Lett. 2017, 27, 2713-2720. (7) (a) Mitchell, S. S.; Rhodes, D.; Bushman, F. D.; Faulkner, D. J. Cyclodidemniserinol Trisulfate, a Sulfated Serinolipid from the Palauan Ascidian Didemnum guttatum That Inhibits HIV-1 Integrase. Org. Lett. 2000, 2, 1605-1607. (b) Marvin, C. C.; Voight, E. A.; Burke, S. D. Synthesis of (+)-Didemniserinolipid B via Ketalization/Ring-Closing Metathesis. Org. Lett. 2007, 9, 5357-5359. (8) Zhang, W.; Tong, R. Synthetic Approaches To Construct the 6,8-DOBCO Framework in Natural Products. J. Org. Chem. 2016, 81, 2203-2212. (9) Trofimov, B. A.; Schmidt, E. Yu.; Ushakov, I. A.; Mikhaleva, A. I.; Zorina, N. V.; Protsuk, N. I.; Senotrusova, E. Yu.; Skital’tseva, E. V.; Kazheva, O. N.; Alexandrov, G. G.; Dyachenko, 20 ACS Paragon Plus Environment

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O. A. One-Pot Assembly of 7-Methylene-6,8-dioxabicyclo[3.2.1]octanes, Congeners of Frontalin, from Ketones and Acetylene. Eur. J. Org. Chem. 2009, 5142-5145. (10) Schmidt, E. Yu.; Trofimov, B. A.; Zorina, N. V.; Mikhaleva, A. I.; Ushakov, I. A.; Skital’tseva, E. V.; Kazheva, O. N.; Alexandrov, G. G.; Dyachenko, O. A. Synthesis of Functionalized 3,4-Dihydropyrans via Rearrangement of the Products of a One-Pot Diastereoselective Assembly of Ketones and Acetylene. Eur. J. Org. Chem. 2010, 35, 67276730. (11) Schmidt, E. Yu.; Bidusenko, I. A.; Ushakov, I. A.; Vashchenko, A. V.; Trofimov, B. A. Decorated Cyclopentadienes from Acetylene and Ketones in Just Two Steps. Org. Lett. 2017, 19, 3127-3130. (12) Schmidt, E. Yu.; Bidusenko, I. A.; Ushakov, I. A.; Protsuk, N. I.; Trofimov, B. A. An Easy Access to Sulfur Derivatives of 6,8-Dioxabicyclo[3.2.1]octanes, Naturally Abundant Scaffolds. Synthesis 2018, 50, 2624-2630. (13) Schmidt, E. Yu.; Tatarinova, I. V.; Protsuk, N. I.; Ushakov, I. A.; Trofimov, B. A. Dioximes of 1,6-Heptanediones from Acetylene and Ketones: Only Three Atom-Economic Steps. Mendeleev Commun. 2018, 28, 143-144. (14) Schmidt, E. Yu.; Tatarinova, I. V.; Ushakov, I. A.; Trofimov, B. A. 2,4,6-Trisubstituted 3,4Dihydropyrans from Acetylene and Ketones: Deacetylation in the KOBut/DMSO System. Mendeleev Commun. 2018, 28, 145-146. (15) Trofimov, B. A.; Schmidt, E. Yu.; Zorina, N. V.; Ivanova, E. V.; Ushakov, I. A. TransitionMetal-Free Superbase-Promoted Stereoselective α‑Vinylation of Ketones with Arylacetylenes: A General Strategy for Synthesis of β,γ-Unsaturated Ketones J. Org. Chem. 2012, 77, 6880− 6886. (16) Dickstein, J. I.; Miller, S. I. Nucleophilic Attacks on Acetylenes. In The Chemistry of the Carbon-Carbon Triple Bond, Part 2; Patai, S., Ed.; John Wiley & Sons, 1978; pp 813-955.


Exploring Acetylene Chemistry: A Transition Metal-Free Route to

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