Visible-Light-Mediated Ring-Opening Strategy for the Regiospecific Allylation/Formylation of Cycloalkanols

Article abstract of DOI:10.1021/acs.joc.8b01225

Here we describe a straightforward and efficient approach for regiospecific introduction of an allyl group into cycloalkanol molecules employing a visible-light-mediated ring-opening strategy. A wide range of distally allylated or formylated ketones is fu

Full text of DOI:10.1021/acs.joc.8b01225

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Article
Visible-Light-Mediated Ring-Opening Strategy for the
Regiospecific Allylation/Formylation of Cycloalkanols
Junlei Wang, Binbin Huang, Chengcheng Shi, Chao Yang, and Wujiong Xia
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.8b01225 • Publication Date (Web): 01 Aug 2018
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Visible-Light-Mediated Ring-Opening Strategy for the
Regiospecific Allylation/Formylation of Cycloalkanols
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Junlei Wang, Binbin Huang, Chengcheng Shi, Chao Yang* and Wujiong Xia
State Key Lab of Urban Water Resource and Environment, Harbin Institute of Technology
(Shenzhen), Shenzhen, China 518055
Abstract
Here we describe a straightforward and efficient approach for regiospecific introduction of an allyl
group into cycloalkanol molecules employing a visibleꢀlightꢀmediated ringꢀopening strategy. A
wide range of distally allylated or formylated ketones are furnished from 1ꢀaryl cycloalkanol
precursors of variable ring sizes, providing a concise and practical access for the modification of
complex natural products. Preliminary mechanistic studies demonstrate that the key Oꢀcentered
radicals mediate the sequential ring cleavage and allylation/formylation.
Introduction
Alkoxyl radicals are vital synthetic intermediates which are not only extensively applied in
mechanistic investigations but also served as versatile reaction intermediates in activation of
unfunctionalized alkanes as well as their adjacent CꢀC bonds.1 However, the production of an
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alkoxyl radical via direct homolysis of an OꢀH bond with high dissociation energy is remarkably
challenging.2 In this regard, considerable efforts have been made in the catalytic oxidation of
alcohols to produce alkoxyl radicals.3 To date, transitionꢀmetal catalyzed methods for alcohol
activation under strong oxidative conditions are widely used for the generation of alkoxyl radicals
(Scheme 1a).4 In 2016, Chen and coꢀworkers reported a visibleꢀlightꢀinduced alcohol oxidation
strategy for alkynylation/alkenylation employing a cyclic iodine(III) reagent as the oxidant
(Scheme 1b).5
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Tertiary cycloalkanols can serve as valuable precursors for regiospecific construction of distally
functionalized ketones through selective homolysis of the strained cyclic CꢀC bonds.6 In 2016,
Knowles and coꢀworkers reported a cyclic alkanols to linear ketones enabled by ProtonꢀCoupled
Electron Transfer process (Scheme 1c).7 Recently, the group of Zuo described a simple cerium(III)
chloride/base catalyzed intermolecular CꢀC bond cleavage/ amination sequence for cyclic alcohols
(Scheme 1d).8 In spite of these elegant contributions, novel catalytic processes to enrich the scope
and utility of this category of transformations are still challenging and in great demand.
ProtonꢀCoupled Electron Transfer (PCET), a process occurs when both an electron and a proton
transfer in a concerted step upon the combined effect of oneꢀelectron oxidation and Bronsted base,
has emerged as a powerful approach across the biochemistry and material domains.9 PCET is of
great potential in the activation of unactivated bonds, which is difficult to achieve using traditional
HAT (Hydrogen Atom Transfer) methods.10, 11, 12 As a part of ongoing work of our group, here we
report an effective, regioselective transformation of cyclic aryl alkanols to a wide range of linear
ketones via alkoxyl intermediates under mild reaction conditions (Scheme 1e).
Scheme 1. Methods for the generation of alkoxyl radical. TM = Transition Metals.
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Results and Discussion
Our initial attempt was started by testing the reaction between 1ꢀ(4ꢀmethoxyphenyl)cyclobutanol
(1a) (Ep = 1.22 V vs Fc/Fc+) and ethyl 2ꢀ((phenylsulfonyl)methyl)acrylate (2a) in the presence of
Ir[dF(CF3)ppy]2(dtbpy)PF6 (2.0 mol%) in dichloromethane (DCM) under the irradiation of a 20 W
white LED (Table 1). A ringꢀopening product (3a) was isolated in 18% yield (entry 1). Then
several photocatalysts were surveyed, among which Ir[dF(CF3)ppy]2(dCF3bpy)PF6 (2.0 mol%)
gave the best result (entries 2ꢀ4). Further screening on bases such as 4ꢀdimethylaminopyridine
(DMAP), Et3N, DBU and collidine indicated that collidine is the most effective one, affording 3a
in 73% yield (entries 5ꢀ8). The influence of solvents was also examined in which
N,NꢀDimethylformamide (DMF) and PhCF3 led to moderate yields (entries 9, 10). Control
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experiments showed that photocatalyst, base, visible light and inert atmosphere are necessary for
this photoredox process (entries 11ꢀ14).
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Table 1. The optimization of reaction conditions.a
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a Unless otherwise noted, reactions were conducted with 0.1 mmol 1a, 0.2 mmol 2a, 0.25 mmol base, 0.002 mmol
c
photocatalyst in 1.0 mL solvent, under the irradiation of a 20 W white LED and N2 atmosphere. b Isolated yield.
d
Reaction performed in the dark. Reaction conducted without degassing. Lutidine = 2, 6ꢀdimethylpyridine.
Collidine = 2,4,6ꢀtrimethylpyridine.
With the optimized conditions established, we next investigated the ring opening/allylation
protocol. The transformation was proved effective to various cycloalkanols, affording allylation
products in moderate to good yields (Scheme 2). Electronꢀrich groups, e.g. methoxyl, substituted
cyclobutanols afforded the corresponding products in moderate yields (3aꢀ3c). The alkyl groups,
t
such as Bu, substituted cyclobutanol also proceeded smoothly to provide the desired products 3d
in good yield. For substrates with fused benzene rings, lower yields were obtained in reaction
systems (3e, 3f). Moreover, a range of cyclobutanols attached to heterocycles were found suitable
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for the procedure, and the corresponding products were acquired in modest yields (3gꢀ3i). The
ringꢀopening products of multisubstituted cyclobutanols, which were difficult to synthesize via
traditional routes owing to the ThorpeꢀIngold Effects,13 were also furnished in moderate to
excellent yields in this protocol (3jꢀ3l).
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Scheme 2. Scope of Different Aryls.a
a Reaction conditions: 0.1 mmol 1a, 0.2 mmol 2a, 0.25 mmol collidine, 2.0 mol % photocatalyst in 1.0 mL DCM,
N2 circumstance, 20 W white LED. Isolated yields are shown.
Scheme 3. Scope of Different Cycloalkanols.a
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a Reaction conditions: 0.1 mmol
DCM, N2 circumstance, 20 W white LED. Isolated yields are shown. b 0.5 mol % photocatalyst.
4
, 0.2 mmol 2a, 0.25 mmol collidine, 2.0 mol % photocatalyst in 1.0 mL
Subsequently, the scope of various ringꢀsized cycloalkanols bearing different functional groups
was examined (Scheme 3A). A series of cycloalkanols with different sized rings were compatible
with the reaction conditions, generating the distally allylation products in good efficiency (5aꢀ5f).
Substrates containing a heteroatom in the ring could also undergo the transformation successfully,
providing ringꢀopening products in moderate to good yields (5g, 5h). Interestingly, in the
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reaction of sulfurꢀcontained substrate 4i, 5i was isolated instead with an exceptional deethylation
process. Substrates bearing an alkyl substitution at the αꢀposition of the hydroxyl group were also
proved viable, furnishing the corresponding products in moderate to good yields (5jꢀ5m).
Scaledꢀup synthesis of 5n was conducted, with the desired product obtained in excellent yield
even with lowered photocatalyst loading to 0.5 mol%. The dihydroindenol derivative 4o was then
examined, and 5o was obtained in 35% yield. To highlight the synthetic utility of this protocol,
further exploration of practicality in the derivative of diosgenin 4p was also carried out, the
allylation reactions took place smoothly on the specific location to give the desired product 5p in
good yield (Scheme 3B).
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Scheme 4. Morita−Baylis−Hillman Acetate as a source of allyl.
To further explore the application of the new strategy, we found that Morita−Baylis−Hillman
reaction partner14 2b could also be accommodated in this process (Scheme 4). Preliminary studies
revealed that the model substrate 1a and 2b are compatible with the reaction conditions, providing
the desired product 6a in 36% yield.
Encouraged by the previous study,15 we wonder whether air could be used as the oxidant in this
ringꢀopening strategy. We were pleased to find that the distally formylated products 7a was
successfully afforded in 45% when DCM was switched to 1,1,1,3,3,3ꢀhexafluoroꢀ2ꢀpropanol
(HFIP) (Scheme 5), whereas no reaction was observed in DCM. We then examined other reaction
media using air as the oxidant and found CF3CH2OH was the ideal solvent (Table S4). Under
optimized conditions, cycloalkanols of different ring sizes (1a, 1e, 4bꢀ4f) all reacted well to
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provide the corresponding products in moderate to good yields (Scheme 5). For substrates with
fused benzene and hetercycle rings, moderate yields are provided in this procedure (7g, 7h).
Scheme 5. Air as a Green Reaction Partner.a
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a Reaction conditions: 0.1 mmol
1, 0.2 mmol 2b, 0.20 mmol lutidine, 2.0 mol % photocatalyst in 1.0 mL
CF3CH2OH, air, 20 W white LED, r.t. Isolated yields are shown.
Scheme 6. Control experiments.
To gain further insights into the mechanism, a radial intermediate trapping experiment was
conducted (Scheme 6a), the reaction was completely inhibited by the radical scavenger
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2,2,6,6ꢀtetramethylꢀ1ꢀpiperidinyloxy (TEMPO), indicating a radical pathway of this process. It is
noteworthy that substrates with aryl substituents that are generally difficult to be oxidized by the
photocatalyst to produce radical cations failed to form allylated products (Scheme 6b). Alternative
reaction partners such as CO and CO2 could not undergo this ringꢀopening process (Scheme 6c).
A detailed description of the mechanism based on the above mechanistic studies as well as current
literature was outlined in Scheme 7.15,16,17 Excitation of the photocatalyst
IrIII[dF(CF3)ppy]2(dCF3bpy)PF6 followed by the process of single electron oxidation of 1a
afforded transient radical cation A and IrII[dF(CF3)ppy]2(dCF3bpy)PF6. An intramolecular
protonꢀcoupled electron transfer process occured with the concomitant formation of the key
alkoxy radical intermediate B by donating a proton to base. Aryl ketone with a distal alkyl radical
C was generated smoothly from the ringꢀopening process owing to the ability of the alkoxyl
radicals that could weaken the adjacent C−C bonds. Radical C could further be trapped by 2a to
give the intermediate D, which was then reduced by [Ir]II[dF(CF3)ppy]2(dCF3bpy)PF6 to afford the
product E and PhSO22ꢀ. In the other process, IrII was oxdized to IrIII by the oxygen in air with the
concomitant formation of [O2]•ꢀ ,and the oxygen radical anion was easily trapped by C to yield the
aldehyde product 7a.
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Scheme 7. Proposed reaction mechanism.
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Conclusion
In summary, an efficient and straightforward method for the construction of distally allylated and
formylated ketones has been developed using photoredox cycle under mild reaction conditions.
We envision that this ringꢀopening strategy will find further applications in synthesis of natural
products and biomolecule studies. Further studies and investigations towards novel application of
alkoxyl radical processes are under way in our laboratory.
Experimental Section
General Information
Commercial reagents were obtained from Aldrich and Energy Chemical Chemicals without further
purification unless otherwise stated. H NMR, 13C NMR were recorded on a Bruker AVꢀ400 or
1
600 (1H NMR at 400 MHz or 600 M, 13C NMR at 100 MHz or 151 M) spectrometers using
tetramethylsilane (TMS) as internal standard. Data are reported as (s = singlet, d = doublet, t =
triplet, q = quadruplet, m = multiplet or unresolved, br = broad signal, coupling constant(s) in Hz,
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integration). High resolution mass spectra (HRMS) were collected on QꢀTOF LC/MS system.
GCꢀMS analysis was conducted on a 7890Aꢀ5975C/Agilent.
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General Procedure for the Synthesis of substrates.
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(1) For substrates 1a-1e, 1j-1l, 4a-4o, 5p:
In a twoꢀneck bottle, a mixture of ArBr (10 mmol, 1 equiv), Mg (15 mmol, 1.5 equiv) and
catalytical amount of iodine in anhydrous THF (25 mL) under N2 atmosphere, subsequently the
mixture was string until the complete formation of the aryl Grignard reagent. And relevant ketone
was added into the reaction mixture at 0 oC, and then the reaction was removed to room
temperature. When the starting materials completely consumed monitored by TLC, the reaction
was quenched using saturated aqueous ammonium chloride solution and extracted with EtOAc.
The organic layers were combined and washed with brine, dried over Na2SO4, concentrated in
vacuo. The residue was purified by a silica gel column (petroleum ether/EtOAc:, 10:1) to afford
the corresponding products.
(2) For substrates 1f, 1g, 1h and 1i:
In a twoꢀneck bottle, ArH (10 mmol, 1 equiv.) was added in anhydrous THF (25 mL) under N2
atmosphere, 4.8 mL BuLi (12 mmol, 1.2 equiv.) was added to the solution at ꢀ78 °C, an hour later,
the reaction system was transfered to room temperature. When the starting materials completely
consumed, reactions were quenched using saturated aqueous ammonium chloride solution and
extracted with EtOAc. The organic layers was combined and washed with brine, dried over
Na2SO4, concentrated in vacuo. The residue was purified by a silica gel column (petroleum
ether/EtOAc:, 10:1) to afford cycloalkanols.
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1-(4-methoxyphenyl)cyclobutan-1-ol (1a). Colorless oil, 85% isolated yield. 1H NMR (400 MHz,
CDCl3): δH 7.42 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 3.81 (s, 3H), 2.54 (ddd, J = 13.2, 8.7,
4.9 Hz, 2H), 2.42ꢀ2.28 (m, 2H), 2.18ꢀ1.89 (m, 2H), 1.64 (dp, J = 11.1, 8.5 Hz, 1H); 13C NMR (151
MHz, CDCl3): δC 158.8, 138.6, 126.6, 113.8, 76.7, 55.4, 36.9, 13.0; GCꢀMS (EI, QMS, m/z): 92.1,
108.1, 135.1, 150.1, 178.1. The spectroscopic data is in agreement with the literature.3d
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1
1-(2,4-dimethoxyphenyl)cyclobutan-1-ol (1b). Colorless oil, 80% isolated yield. H NMR (600
MHz, CDCl3): δH 7.22 (d, J = 8.3 Hz, 1H), 6.50 (s, 1H), 6.46 (d, J = 8.3 Hz, 1H), 3.85 (s, 3H),
3.81 (s, 3H), 3.47 (s, 1H), 2.52ꢀ2.45 (m, 2H), 2.38ꢀ2.30 (m, 2H), 2.05ꢀ1.97 (m, 1H), 1.67ꢀ1.59 (m,
1H); 13C NMR (151 MHz, CDCl3): δC 160.3, 158.5, 126.1, 126.1, 103.5, 99.4, 76.4, 55.5, 55.4,
35.3, 14.2; GCꢀMS (EI, QMS, m/z): 122.1, 152.1, 165.1, 180.1, 208.1; HRMS (ESI): calcd for
C12H17O3 , (M+H)+, 209.1172, found, 209.1179.
+
1
1-(3,5-dimethoxyphenyl)cyclobutan-1-ol (1c). Colorless oil, 72% isolated yield. H NMR (400
MHz, CDCl3): δH 6.65 (d, J = 2.2 Hz, 1H), 6.38 (t, J = 2.1 Hz, 1H), 3.80 (s, 3H), 2.59ꢀ2.48 (m,
1H), 2.35 (ddd, J = 17.0, 9.9, 6.1 Hz, 1H), 2.16 (s, 1H), 2.07ꢀ1.95 (m, 1H), 1.77ꢀ1.64 (m, 1H); 13
C
NMR (100 MHz, CDCl3): δC 161.0, 149.0, 103.3, 99.1, 77.2, 55.5, 36.9, 13.2; GCꢀMS (EI, QMS,
+
m/z): 137.1, 152.1, 165.1,180.1, 208.1; HRMS (ESI): calcd for C12H17O3 , (M+H)+, 209.1172,
found, 209.1169.
1
1-(4-(tert-butyl)phenyl)cyclobutan-1-ol (1d). White Solid, 83％ isolated yield . H NMR (400
MHz, CDCl3): δH 7.43 (q, J = 8.6 Hz, 4H), 2.63 ꢀ 2.54 (m, 2H), 2.37 (ddd, J = 12.5, 9.4, 7.7 Hz,
2H), 2.13 (s, 1H), 2.07ꢀ1.96 (m, 1H), 1.76ꢀ1.63 (m, 1H), 1.35 (s, 9H); 13C NMR (100 MHz,
CDCl3): δC 150.2, 143.4, 125.4, 124.9, 76.9, 36.8, 34.6, 31.5, 13.1; GCꢀMS (EI, QMS, m/z): 134.0,
147.0, 161.1, 176.0, 204.1. The spectroscopic data is in agreement with the literature. 3d
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1-(naphthalen-2-yl)cyclobutan-1-ol (1e). Colorless oil, 80% isolated yield. 1H NMR (600 MHz,
CDCl3): δH 7.95ꢀ7.81 (m, 4H), 7.65 (d, J = 8.5 Hz, 1H), 7.49 (dd, J = 12.3, 6.3 Hz, 2H), 2.76ꢀ2.63
(m, 2H), 2.52ꢀ2.39 (m, 2H), 2.07 (ddd, J = 14.8, 10.4, 5.0 Hz, 2H), 1.80ꢀ1.71 (m, 1H); 13C NMR
(151 MHz, CDCl3): δC 141.4, 131.2, 130.8, 126.7, 126.3, 125.7, 124.3, 124.1, 122.1, 121.2, 34.9,
11.2; GCꢀMS (EI, QMS, m/z): 128.1, 141.1, 155.1, 170.1, 198.1. The spectroscopic data is in
agreement with the literature.3c
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1-(phenanthren-9-yl)cyclobutan-1-ol (1f). H NMR (400 MHz, CDCl3): δH 8.77 (d, J = 8.1 Hz,
1H), 8.69 (d, J = 8.2 Hz, 1H), 8.40 (d, J = 8.1 Hz, 1H), 7.92 (d, J = 7.7 Hz, 1H), 7.80 (s, 1H), 7.73
ꢀ7.61 (m, 4H), 2.95 (dd, J = 14.9, 10.9 Hz, 2H), 2.69 (dd, J = 18.8, 9.1 Hz, 2H), 2.38 (s, 1H),
2.27ꢀ2.14 (m, 1H), 1.85ꢀ1.71 (m, 1H); 13C NMR (151 MHz, CDCl3): δC 138.3, 131.7, 131.1, 130.5,
129.7, 129.1, 127.2, 127.1, 126.9, 126.4, 126.4, 124.2, 123.4, 122.5, 78.6, 36.7, 14.6; GCꢀMS (EI,
QMS, m/z): 165.1, 203.1, 215.1, 232.1, 248.1. The spectroscopic data is in agreement with the
literature.7
1-(benzofuran-2-yl)cyclobutan-1-ol (1g). Colorless oil, 59% isolated yield. 1H NMR (400 MHz,
CDCl3): δH 7.58 (dd, J = 7.5, 0.7 Hz, 1H), 7.50 (d, J = 8.2 Hz, 1H), 7.28 (dtd, J = 21.3, 7.3, 1.1 Hz,
2H), 6.70 (d, J = 0.6 Hz, 1H), 2.73ꢀ2.56 (m, 3H), 2.53ꢀ2.37 (m, 2H), 2.05ꢀ1.93 (m, 1H), 1.82 (dp,
J = 11.2, 8.7 Hz, 1H); 13C NMR (100 MHz, CDCl3): δH 160.8, 155.1, 128.3, 124.3, 122.9, 121.2,
111.3, 101.6, 72.7, 35.7, 12.9; GCꢀMS (EI, QMS, m/z): 118.1, 131.1, 145.0, 160.1, 188.1. The
spectroscopic data is in agreement with the literature. 3c
1
1-(benzo[b]thiophen-2-yl)cyclobutan-1-ol (1h). White solid, 68% isolated yield. H NMR (400
MHz, CDCl3): δH 7.84 (d, J = 7.8 Hz, 1H), 7.79ꢀ7.73 (m, 1H), 7.35 (dtd, J = 16.4, 7.2, 1.2 Hz, 2H),
7.29 (d, J = 2.7 Hz, 1H), 2.64 (dddd, J = 11.3, 9.0, 4.5, 2.5 Hz, 2H), 2.57ꢀ2.46 (m, 2H), 2.44 (s,
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1H), 2.02 (dtt, J = 11.3, 9.3, 4.5 Hz, 1H), 1.85 (dp, J = 11.3, 8.6 Hz, 1H); 13C NMR (100 MHz,
CDCl3): δC 152.2, 139.8, 139.8, 124.4, 124.3, 123.6, 122.6, 119.3, 75.3, 38.3, 12.9; GCꢀMS (EI,
QMS, m/z): 89.0, 134.0, 147.0, 176.0, 204.1. The spectroscopic data is in agreement with the
literature. 7
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1-(1-methyl-1H-indol-2-yl)cyclobutan-1-ol (1i). White solid, 20% isolated yield. 1H NMR (400
MHz, CDCl3): δH 7.44 (d, J = 7.3 Hz, 2H), 7.35 (t, J = 7.5 Hz, 2H), 7.28 (d, J = 7.4 Hz, 1H), 6.67
(d, J = 16.0 Hz, 1H), 6.52 (d, J = 16.0 Hz, 1H), 2.40ꢀ2.21 (m, 4H), 1.99ꢀ1.85 (m, 2H), 1.78ꢀ 1.66
(m, 1H); 13C NMR (151 MHz, CDCl3): δC 137.0, 134.1, 128.7, 127.6, 126.9, 126.6, 75.3, 36.6,
12.4; GCꢀMS (EI, QMS, m/z): 144.1, 154.1, 168.1, 183.1, 201.1. The spectroscopic data is in
agreement with the reported literature. 7
1
3-(benzyloxy)-1-(4-methoxyphenyl)cyclobutan-1-ol (1j). Colorless oil, 47% isolated yield. H
NMR (400 MHz, CDCl3): δH 7.39 (d, J = 8.7 Hz, 2H), 7.35 (d, J = 4.3 Hz, 4H), 7.30 (dt, J = 9.2,
4.6 Hz, 1H), 6.90 (d, J = 8.7 Hz, 2H), 4.47 (d, J = 6.3 Hz, 2H), 3.84ꢀ3.73 (m, 4H), 2.97ꢀ2.89 (m,
2H), 2.50 ꢀ2.41 (m, 2H), 2.29 (s, 1H); 13C NMR (151 MHz, CDCl3): δC 159.0, 138.2, 137.6, 128.6,
128.0, 127.8, 126.8, 114.0, 70.6, 70.0, 65.4, 55.4, 45.3; GCꢀMS (EI, QMS, m/z): 199.1, 214.2,
+
244.2，277.2,,284.1; HRMS (ESI): calcd for C18H21O3 , (M+H)+, 285.1485, found, 285.1494.
methyl 3-hydroxy-3-(4-methoxyphenyl)cyclobutane-1-carboxylate (1k). White solid, 48%
isolated yield. 1H NMR (600 MHz, CDCl3): δH 7.42 (d, J = 8.6 Hz, 2H), 6.91 (d, 2H), 3.96ꢀ3.80 (s,
3H), 3.73 (s, J = 9.0 Hz, 3H), 2.90 (s, 1H), 2.89ꢀ2.84 (m, 2H), 2.79 (dd, J = 15.4, 7.3 Hz, 2H),
2.67ꢀ2.59 (m, 2H); 13C NMR (151 MHz, CDCl3): δC 176.6, 159.1, 137.0, 126.6, 114.0, 73.3, 55.4,
52.2, 40.9, 29.6; HRMS (ESI): calcd for C13H16O4Na+, (M+ Na)+, 259.0941, found, 259.0934.
6-(4-methoxyphenyl)bicyclo[3.2.0]hept-2-en-6-ol (1l). Colorless oil, 72% isolated yield. 1H
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NMR (400 MHz, CDCl3): δH 7.45ꢀ7.35 (m, 2H), 6.90 (d, J = 8.7 Hz, 2H), 5.96 (s, 2H), 3.81 (s,
3H), 3.36 (t, J = 7.9 Hz, 1H), 3.19 (t, J = 7.7 Hz, 1H), 2.94 (dd, J = 13.0, 8.4 Hz, 1H), 2.88ꢀ2.79
(m, 1H), 2.52 (dd, J = 17.4, 8.7 Hz, 1H), 2.14 (s, 1H), 2.08 (dd, J = 13.0, 3.3 Hz, 1H); 13C NMR
(151 MHz, CDCl3): δC 158.6, 139.9, 135.7, 133.0, 126.2, 113.7, 76.5, 55.4, 48.0, 44.5, 39.6, 33.1;
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GCꢀMS (EI, QMS, m/z): 148.1,173.1,188.2, 201.2, 216.2; HRMS (ESI): calcd for C14H17O2 ,
(M+H)+, 217.1223, found, 217.1228.
1-phenylcyclobutan-1-ol (1m). 1H NMR (400 MHz, CDCl3): δH 7.51 (d, J = 7.7 Hz, 2H), 7.39 (t,
J = 7.6 Hz, 2H), 7.29 (t, J = 7.3 Hz, 1H), 2.68ꢀ2.52 (m, 2H), 2.50ꢀ2.32 (m, 2H), 2.16 (s, 1H),
2.09ꢀ1.99 (m, 1H), 1.79ꢀ1.60 (m, 1H); 13C NMR (151 MHz, CDCl3): δC 146.3, 128.5, 127.3, 125.1,
77.08, 36.9, 13.1; GCꢀMS (EI, QMS, m/z): 78.1, 105.1, 120.1, 148.1; The spectroscopic data is in
agreement with the reported literature.3d
1-mesitylcyclobutan-1-ol (1n). White Solid, 75%isolated yield. 1H NMR (400 MHz, CDCl3): δH
6.81 (s, 2H), 2.80ꢀ2.70 (m, 2H), 2.55ꢀ2.46 (m, 2H), 2.34 (s, 6H), 2.26 (s, 3H), 2.00 (s, 1H),
1.87ꢀ1.77 (m, 1H); 13C NMR (100 MHz, CDCl3): δC 139.6, 136.7, 136.6, 130.6, 81.6, 39.4, 21.7,
20.7, 17.0; GCꢀMS (EI, QMS, m/z): 115.1, 129.1, 144.1, 157.1, 190.0; HRMS (ESI): calcd for
C13H19O+, (M+H)+, 191.1430, found, 191.1434.
1
1-(3,5-difluorophenyl)cyclobutan-1-ol (1o). H NMR (400 MHz, CDCl3): δH 7.97 (s, 2H), 7.80
(s, 1H), 2.58 (ddd, J = 12.9, 8.9, 5.6 Hz, 2H), 2.49ꢀ2.38 (m, 2H), 2.31 (d, J = 6.3 Hz, 1H),
2.21ꢀ2.08 (m, 1H), 1.90ꢀ1.74 (m, 1H); 13C NMR (151 MHz, CDCl3): δC 164.1 (d, J = 12.6 Hz),
162.4 (d, J = 12.7 Hz), 150.7 (s), 108.1 (dd, J = 20.4, 5.1 Hz), 102.6 (t, J = 25.4 Hz), 76.6, 37.3,
13.0; GCꢀMS (EI, QMS, m/z): 105.1, 120.1, 148.1, 156.1, 184.1; HRMS (ESI): calcd for
C10H11F2O+, (M+H)+, 185.0772, found, 185.0773.
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1-(3,5-bis(trifluoromethyl)phenyl)cyclobutan-1-ol (1p). 1H NMR (400 MHz, CDCl3): δH 7.04 (t,
J = 6.5 Hz, 2H), 6.72 (t, J = 8.8 Hz, 2H), 2.55ꢀ2.46 (m, 2H), 2.43ꢀ2.33 (m, 2H), 2.29 (s, 1H),
2.14ꢀ2.01 (m, 1H), 1.84ꢀ1.71 (m, 1H); 13C NMR (151 MHz, CDCl3): δC 149.0, 131.8 (q, J = 33.1
Hz), 125.4, 125.4, 123.6 (q, J = 272.7 Hz), 121.2 (dd, J = 7.5, 3.8 Hz), 121.3, 121.2, 121.2, 76.6,
37.6, 13.1; GCꢀMS (EI, QMS, m/z): 142.1, 157.1, 241.0, 256.1, 284.1; HRMS (ESI): calcd for
C12H11F6O+, (M+H)+, 285.0709, found, 285.0712.
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1-(4-methoxyphenyl)cyclopropan-1-ol (4a). Colorless oil, 76% isolated yield. H NMR (400
MHz, CDCl3): δH 7.29 (d, J = 7.5 Hz, 2H), 6.90 (d, J = 6.7 Hz, 2H), 3.83 (s, 3H), 2.38 (s, 1H),
1.22 (s, 2H), 0.99 (s, 2H); 13C NMR (151 MHz, CDCl3): δC 158.5, 136.3, 126.5, 113.9, 56.8, 55.5,
16.9; GCꢀMS (EI, QMS, m/z): 64.1, 92, 107.1, 135.0, 164.0. The spectroscopic data is in
agreement with the literature.3d
1
1-(4-methoxyphenyl)cyclopentan-1-ol (4b). Colorless oil, 88% isolated yield. H NMR (600
MHz, CDCl3): δH 7.40 (d, J = 7.6 Hz, 2H), 6.86 (d, J = 7.6 Hz, 2H), 3.79 (s, 3H), 1.96 (s, 6H),
1.80 (t, 2H), 1.65 (t, 2H); 13C NMR (151 MHz, CDCl3): δC 158.5, 139.3, 126.5, 113.6, 83.3, 55.4,
41.6, 23.8; GCꢀMS (EI, QMS, m/z): 115.1, 128.1, 159.1, 174.1, 192.1. The spectroscopic data is in
agreement with the literature. 7
1-(4-methoxyphenyl)cyclohexan-1-ol (4c). Colorless oil, 74% isolated yield. 1H NMR (600 MHz,
CDCl3): δH 7.43 (d, J = 8.6 Hz, 2H), 6.88 (d, J = 8.6 Hz, 2H), 3.80 (s, 3H), 1.87ꢀ1.67 (m, 8H),
1.60 (s, 2H), 1.35ꢀ1.24 (m, 1H); 13C NMR (151 MHz, CDCl3): δC 158.4, 125.9, 113.6, 72.9, 55.4,
55.4, 39.0, 25.6, 22.4; GCꢀMS (EI, QMS, m/z): 135.1, 150.1, 163.1, 188.2, 206.2. The
spectroscopic data is in agreement with the literature. 7
1
1-(4-methoxyphenyl)cycloheptan-1-ol (4d). Colorless oil, 66% isolated yield. H NMR (400
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MHz, CDCl3): δH 7.44 (d, J = 8.6 Hz, 2H), 6.89 (d, J = 8.6 Hz, 2H), 3.82 (s, 3H), 2.08 (dd, J =
14.2, 10.8 Hz, 2H), 1.92 (dd, J = 14.5, 8.1 Hz, 2H), 1.81 (dd, J = 23.9, 11.4 Hz, 2H), 1.75ꢀ1.69 (m,
2H), 1.65ꢀ1.53 (m, 4H); 13C NMR (151 MHz, CDCl3): δC 158.3, 143.0, 125.9, 113.5, 76.7, 55.4,
43.4, 29.3, 22.6; GCꢀMS (EI, QMS, m/z): 135.0, 159.1, 174.1, 202.1, 220.0. The spectroscopic
data is in agreement with the literature. 7
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1-(4-methoxyphenyl)cyclooctan-1-ol (4e). Colorless oil, 58% isolated yield. 1H NMR (600 MHz,
CDCl3): δH 7.43 (d, J = 7.1 Hz, 2H), 6.87 (d, J = 7.1 Hz, 2H), 3.80 (s, 3H), 2.03 (dd, J = 14.8, 8.0
Hz, 2H), 1.99ꢀ1.92 (dd, 2H), 1.71 (m, 5H), 1.54 (m, 6H); 13C NMR (151 MHz, CDCl3): δC 158.4,
141.3, 126.4, 113.5, 76.5, 55.4, 37.9, 28.5, 24.6, 22.2; GCꢀMS (EI, QMS, m/z): 155.1, 167.1,
183.1, 198.1, 234.1. The spectroscopic data is in agreement with the literature.7
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1-(4-methoxyphenyl)cyclododecan-1-ol (4f). White solid, 82% isolated yield. H NMR (400
MHz, CDCl3): δH 7.42 (d, J = 8.5 Hz, 2H), 6.88 (d, J = 8.5 Hz, 2H), 3.83 (s, 3H), 1.87 (t, J = 7.2
Hz, 4H), 1.40 (d, J = 9.9 Hz, 16H), 1.23 (d, J = 10.3 Hz, 2H); 13C NMR (151 MHz, CDCl3): δC
158.4, 140.7, 126.5, 113.3, 76.3, 55.4, 35.6, 26.5, 26.2, 22.6, 22.3, 20.1; GCꢀMS (EI, QMS, m/z):
135.1, 150.1, 245.1, 272.1, 290.1. The spectroscopic data is in agreement with the literature.7
1
4-(4-methoxyphenyl)tetrahydro-2H-pyran-4-ol (4g). White solid, 58% isolated yield. H NMR
(600 MHz, CDCl3): δH 7.40 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 3.91 (td, J = 11.8, 2.0 Hz,
2H), 3.84 (dd, J = 11.3, 4.0 Hz, 2H), 3.80 (s, 3H), 2.13 (td, J = 13.1, 5.1 Hz, 2H), 1.77 (dd, J = 7.8,
3.8 Hz, 1H), 1.72ꢀ1.65 (m, 2H); 13C NMR (151 MHz, CDCl3): δC 158.8, 140.4, 125.8, 113.8,
70.30, 64.1, 55.4, 38.9; GCꢀMS (EI, QMS, m/z): 77.1, 135.0, 150.1, 190.1, 208.1; HRMS (ESI):
+
calcd for C12H17O3 , (M+H)+, 209.1172, found, 209.1167.
ethyl 4-hydroxy-4-(4-methoxyphenyl)piperidine-1-carboxylate (4h). White solid, 35% isolated
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yield. 1H NMR (400 MHz, CDCl3): δH 7.40 (d, J = 8.8 Hz, 2H), 6.90 (d, J = 8.8 Hz, 2H), 4.16 (q,
J = 7.1 Hz, 2H), 4.06 (s, 2H), 3.82 (s, 3H), 3.30 (t, J = 11.7 Hz, 2H), 1.98 (s, 2H), 1.85ꢀ1.67 (m,
3H), 1.29 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3): δC 158.8, 155.7, 140.3, 125.8, 113.8,
71.1, 61.4, 55.4, 40.1, 38.1, 14.8; GCꢀMS (EI, QMS, m/z): 121.1, 145.1, 232.2, 261.1, 279.1;
HRMS (ESI): calcd for C15H21NO4Na+, (M+Na)+, 302.1363, found, 302.1363.
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1-(4-methoxyphenyl)cyclobutan-1-ol (4i). Red solid, 48% isolated yield. H NMR (400 MHz,
CDCl3): δH 7.39 (d, J = 8.5 Hz, 2H), 6.89 (d, J = 8.5 Hz, 2H), 3.80 (s, 3H), 3.19 (t, J = 13.0 Hz,
2H), 2.46 (d, J = 13.6 Hz, 2H), 2.20ꢀ2.08 (m, 2H), 2.01 (d, J = 14.0 Hz, 2H), 1.53 (s, 1H); 13C
NMR (151 MHz, CDCl3): δC 158.7, 141.5, 125.6, 113.8, 71.6, 55.4, 39.8, 24.4; GCꢀMS (EI, QMS,
m/z): 135.1, 163.1, 177.1, 196.1, 224.1; HRMS (ESI): calcd for C12H17O2S+, (M+H)+, 225.0944,
found, 225.0938.
1-(4-methoxyphenyl)-2,4,4-trimethylcyclopentan-1-ol (4j). Colorless oil, 64% isolated yield. 1H
NMR (600 MHz, CDCl3): δH 7.40ꢀ7.34 (m, 1H), 6.87 (d, J = 8.8 Hz, 1H), 3.80 (s, 2H), 2.47ꢀ2.33
(m, 1H), 1.93 (d, J = 14.4 Hz, 1H), 1.86 (d, J = 14.4 Hz, 1H), 1.72ꢀ1.65 (m, 1H), 1.51 (s, 1H),
1.19 (s, 1H), 1.12 (s, 2H), 0.80 (d, J = 6.7 Hz, 1H), 13C NMR (151 MHz, CDCl3): δC 158.2, 138.5,
126.2, 113.5, 85.1, 58.8, 55.4, 48.2, 44.5, 35.8, 32.2, 11.7; GCꢀMS (EI, QMS, m/z): 135.1, 150.1,
+
191.1, 219.2, 234.2; HRMS (ESI): calcd for C15H23O2 , (M+H)+, 235.1693, found, 235.1692.
2-isopropyl-1-(4-methoxyphenyl)-5-methylcyclohexan-1-ol (4k). Colorless oil, 55% isolated
yield. 1H NMR (400 MHz, CDCl3): δH 7.36 (d, J = 7.5 Hz, 2H), 6.88 (d, J = 8.1 Hz, 2H), 3.81 (s,
3H), 1.85 (t, J = 12.4 Hz, 2H), 1.67ꢀ1.49 (m, 6H), 1.41 (t, J = 13.0 Hz, 1H), 1.04 (q, J = 12.2 Hz,
1H), 0.89 (d, J = 6.2 Hz, 3H), 0.82 (d, J = 6.8 Hz, 3H), 0.74 (d, J = 6.9 Hz, 3H); 13C NMR (151
MHz, CDCl3): δC 158.0, 141.0, 125.8, 113.5, 78.3, 55.3, 51.9, 50.1, 35.3, 28.7, 26.7, 23.9, 22.4,
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agreement with the literature.7
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(3aS,4S,5S,7S,7aS)-5-(4-methoxyphenyl)octahydro-1H-4,7-methanoinden-5-ol (4l). Colorless
oil, 65% isolated yield. 1H NMR (600 MHz, CDCl3): δH 7.51ꢀ7.40 (d, 2H), 6.91ꢀ6.82 (d, 2H), 3.80
(s, 3H), 2.78 (q, J = 8.7 Hz, 1H), 2.33 (dd, J = 13.1, 5.1 Hz, 2H), 2.07 (q, J = 8.7 Hz, 1H), 2.02 (d,
J = 5.0 Hz, 1H), 1.98ꢀ1.88 (m, 2H), 1.71 (dd, J = 12.2, 6.2 Hz, 1H), 1.67 (s, 1H), 1.41 (d, J = 11.3
Hz, 2H), 1.34ꢀ1.24 (m, 1H), 1.22 (d, J = 10.3 Hz, 1H), 1.08ꢀ1.00 (m, 1H), 0.96 (tdd, J = 12.6, 8.9,
6.6 Hz, 1H); 13C NMR (151 MHz, CDCl3): δC 158.4, 141.3, 127.4, 113.6, 80.2, 55.4, 51.7, 47.8,
46.1, 42.1, 39.5, 32.7, 32.4, 32.0, 27.5; GCꢀMS (EI, QMS, m/z): 135.1, 150.1, 172.1, 241.2, 258.1;
HRMS (ESI): calcd for C17H22O2Na+, (M+Na)+, 281.1512, found, 281.1502.
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(1r,3r,5r,7r)-2-(4-methoxyphenyl)adamantan-2-ol (4m). White solid, 88% isolated yield. H
NMR (600 MHz, CDCl3): δH 7.46 (d, J = 8.6 Hz, 2H), 6.90 (d, J = 8.6 Hz, 2H), 3.81 (s, 3H), 2.53
(s, 2H), 2.39 (d, J = 12.2 Hz, 2H), 1.90 (s, 1H), 1.72 (d, J = 13.4 Hz, 9H), 1.48 (s, 1H); 13C NMR
(151 MHz, CDCl3): δC 158.7, 137.7, 126.8, 114.0, 75.4, 55.4, 37.8, 35.9, 35.0, 33.2, 27.6, 27.0;
GCꢀMS (EI, QMS, m/z): 121.1, 150.1, 227.2, 241.2, 258.1; HRMS (ESI): calcd for C17H22O2Na+,
(M+Na)+, 281.1512, found, 281.1513.
(1S,2R,4R)-2-(4-methoxyphenyl)-1,7,7-trimethylbicyclo[2.2.1]heptan-2-ol (4n). White solid,
88% isolated yield. 1H NMR (400 MHz, CDCl3): δH 7.47 (d, J = 8.9 Hz, 2H), 6.89 (d, J = 8.9 Hz,
2H), 3.84 (s, 3H), 2.30 (d, J = 13.9 Hz, 1H), 2.26ꢀ2.15 (m, 1H), 1.91 (t, J = 4.3 Hz, 1H), 1.82 (s,
1H), 1.75 (ddt, J = 16.9, 12.8, 3.8 Hz, 1H), 1.29 (s, 3H), 1.27ꢀ1.16 (m, 2H), 0.93 (d, J = 2.8 Hz,
6H), 0.91ꢀ0.83 (m, 1H); 13C NMR (100 MHz, CDCl3): δC 158.5, 138.4, 128.0, 112.9, 83.4, 55.4,
53.6, 50.4, 45.7, 31.4, 26.7, 21.8, 21.8, 10.0; GCꢀMS (EI, QMS, m/z): 135.1, 150.1, 214.2, 242.2,
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260.1. The spectroscopic data is in agreement with the literature.7
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1-(4-methoxyphenyl)-2,3-dihydro-1H-inden-1-ol (4o). Colorless oil, 85% isolated yield. 1H
NMR (400 MHz, CDCl3): δH 7.38ꢀ7.29 (m, 4H), 7.28ꢀ7.19 (m, 1H), 7.12 (d, J = 7.4 Hz, 1H), 6.86
(d, J = 7.9 Hz, 2H), 3.81 (s, 3H), 3.21ꢀ3.07 (m, 1H), 3.00ꢀ2.85 (m, 1H), 2.57ꢀ2.39 (m, 2H), 2.07 (s,
1H); 13C NMR (151 MHz, CDCl3): δC 158.6, 148.2, 144.1, 138.6, 128.5, 127.1, 127.1, 125.1,
124.07, 113.5, 85.3, 55.4, 44.9, 29.9; GCꢀMS (EI, QMS, m/z): 152.1, 178.1, 207.1, 222.1, 240.1;
HRMS (ESI): calcd for C16H16O2 Na+, (M+H)+, 263.1043, found, 263.1039.
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(5'R,6aR,6bS,8aS,8bR,9S,11aS,12aS,12bS)-4-(4-methoxyphenyl)-5',6a,8a,9-tetramethyl-1,3,3
',4,4',5,5',6,6a,6b,6',7,8,8a,8b,9,11a,12,12a,12b-icosahydrospiro[naphtho[2',1':4,5]indeno[2,1-
1
b]furan-10,2'-pyran]-4-ol (4p). Colorless oil, 50% isolated yield. H NMR (400 MHz, CDCl3):
δH 7.47 (d, J = 8.7 Hz, 2H), 6.91 (d, J = 8.7 Hz, 2H), 5.48 (d, J = 4.8 Hz, 1H), 4.45 (dd, J = 14.9,
7.5 Hz, 1H), 3.83 (d, J = 5.5 Hz, 3H), 3.55ꢀ3.47 (m, 1H), 3.41 (t, J = 10.9 Hz, 1H), 2.82 (d, J =
14.4 Hz, 1H), 2.16ꢀ2.00 (m, 1H), 1.98 (s, 1H), 1.93ꢀ1.88 (t, 1H), 1.88ꢀ1.79 (m, 3H), 1.79ꢀ1.75 (m,
1H), 1.74ꢀ1.69 (m, 2H), 1.68ꢀ1.58 (m, 7H), 1.57ꢀ1.44 (m, 3H), 1.32 (ddd, J = 16.9, 12.0, 5.8 Hz,
2H), 1.25ꢀ1.11 (m, 6H), 1.01 (d, J = 6.9 Hz, 3H), 0.86ꢀ0.79 (m, 6H); 13C NMR (151 MHz, CDCl3):
δC 158.5, 140.5, 140.0, 125.9, 124.3, 113.6, 109.4, 80.9, 73.4, 67.0, 62.2, 56.6, 55.4, 50.4, 46.58,
41.7, 40.4, 39.9, 36.9, 35.5, 34.9, 32.3, 32.0, 31.6, 31.5, 30.4, 28.9, 20.9, 18.9, 17.3, 16.4, 14.7;
HRMS (ESI): calcd for C34H48O4Na +, (M+Na)+, 543.3445, found, 543.3445.
General Procedures for Allylation of Cycloalkanols
Procedure A: Allylation of cycloalkanol reactions were conducted as follows: In a 10 mL bottom
flask, containing a magnetic stirring bar, the respective cycloalkanols (0.1 mmol, 1 equiv), ethyl
2ꢀ((phenylsulfonyl)methyl)acrylate 2a/2b (0.2 mmol, 2 equiv), collidine (0.25 mmol, 2 equiv) and
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Ir[dF(CF3)ppy]2(dCF3bpy)PF6 was dissolved in 1 mL DCM, and the reaction system was
irradiated under the 20 W White LED at room temperature. After the reaction, the solvents was
removed under reduced pressure and purified by flash column chromatography (10%
EtOAc/hexaneꢀ30% EtOAc/hexane) to give the allylation products.
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Procedure B : Formylation of Cycloalkanol reactions were conducted as follows: In a 10 mL
bottom flask, containing a magnetic stirring bar, the respective Cycloalkanols (0.1 mmol, 1 equiv),
2,6ꢀLutidine (0.25 mmol, 2.5 equiv) and Ir[dF(CF3)ppy]2(dCF3bpy)PF6 (2.0 mol％)was dissolved
in 1 mL CF3CH2OH, and the reaction system was irradiated under the 20 W White LED at room
temperature. After the reaction, the solvents was removed under reduced pressure and purified by
flash column chromatography (10% EtOAc/hexaneꢀ30% EtOAc/hexane) to give the allylation
products.
ethyl 7-(4-methoxyphenyl)-2-methylene-7-oxoheptanoate (3a). Procedure A: yellow oil, 21.2
1
mg, 73% isolated yield. H NMR (400 MHz, CDCl3): δH 7.98ꢀ7.88 (m, 2H), 6.97ꢀ6.88 (m, 2H),
6.13 (d, J = 1.3 Hz, 1H), 5.53 (d, J = 1.3 Hz, 1H), 4.27 ꢀ 4.13 (t, 2H), 3.86 (s, 3H), 2.93 (t, J = 7.4
Hz, 2H), 2.34 (t, J = 7.5 Hz, 2H), 1.82ꢀ 1.68 (m, 2H), 1.62 ꢀ1.49 (m, 2H), 1.28 (t, J = 7.1 Hz, 3H);
13C NMR (100 MHz, CDCl3): δC 198.9, 167.4, 163.4, 140.7, 130.4, 130.2, 124.7, 113.8, 60.7, 55.5,
38.1, 31.8, 28.2, 24.1, 14.3; GCꢀMS (EI, QMS, m/z): 135.1, 150.1, 245.1, 272.1, 290.1; HRMS
+
(ESI): calcd for C17H22NaO4 , (M+Na)+, 313.1410, found, 313.1411.
ethyl 7-(2,4-dimethoxyphenyl)-2-methylene-7-oxoheptanoate (3b). Procedure A: yellow oil,
24.3 mg, 76% isolated yield. 1H NMR (600 MHz, CDCl3): δH 7.77 (d, J = 8.7 Hz, 1H), 6.50 (d, J
= 8.7 Hz, 1H), 6.43 (s, 1H), 6.12 (s, 1H), 5.51 (s, 1H), 4.18 (q, J = 7.0 Hz, 2H), 3.86 (s, 3H), 3.83
(s, 3H), 2.94 (t, J = 7.3 Hz, 2H), 2.32 (t, J = 7.6 Hz, 2H), 1.73ꢀ1.65 (m, 2H), 1.57ꢀ1.48 (m, 2H),
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1.28 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3): δC 200.6, 167.4, 164.3, 160.7, 140.8, 132.7,
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124.5, 121.3, 105.1, 98.4, 60.6, 55.6, 55.5, 43.5, 31.8, 28.2, 24.2, 14.3; GCꢀMS (EI, QMS, m/z):
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135.0, 163.0, 229.1, 302.1, 320.1; HRMS (ESI): calcd for C18H25O5 , (M+H)+, 321.1697, found,
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321.1693.
ethyl 7-(3,5-dimethoxyphenyl)-2-methylene-7-oxoheptanoate (3c). Procedure A: colorless oil,
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22.7 mg, 71% isolated yield. H NMR (600 MHz, CDCl3): δH 7.09 (s, 2H), 6.64 (s, 1H), 6.15 (s,
1H), 5.54 (s, 1H), 4.26ꢀ4.12 (q, 2H), 3.84 (s, 6H), 2.95 (t, J = 6.6 Hz, 2H), 2.36 (t, J = 7.1 Hz, 2H),
1.81ꢀ1.72 (m, 2H), 1.62ꢀ1.52 (m, 2H), 1.30 (t, J = 6.5 Hz, 3H); 13C NMR (151 MHz, CDCl3): δC
200.0, 167.4, 161.0, 140.7, 139.1, 124.8, 106.0, 105.2, 60.7, 55.7, 38.5, 31.8, 28.1, 24.0, 14.3;
+
GCꢀMS (EI, QMS, m/z): 165.0, 180.0, 229.1, 302.1, 320.1; HRMS (ESI): calcd for C18H25O5 ,
(M+H)+, 321.1697, found, 321.1695.
ethyl 7-(4-(tert-butyl)phenyl)-2-methylene-7-oxoheptanoate (3d). Procedure A: colorless oil,
25.3 mg, 80% isolated yield. 1H NMR (600 MHz, CDCl3): δH 7.89 (d, J = 7.9 Hz, 2H), 7.47 (d, J =
7.9 Hz, 2H), 6.14 (s, 1H), 5.54 (s, 1H), 4.20 (q, J = 7.1 Hz, 2H), 2.97 (t, J = 7.2 Hz, 2H), 2.35 (t, J
= 7.4 Hz, 2H), 1.80ꢀ1.73 (m, 2H), 1.57 (dd, J = 15.8, 8.0 Hz, 2H), 1.34 (s, 9H), 1.29 (t, J = 7.1 Hz,
3H); 13C NMR (151 MHz, CDCl3): δC 200.1, 167.4, 156.8, 140.7, 134.6, 128.2, 125.7, 124.8, 60.7,
38.4, 35.2, 31.9, 31.2, 28.2, 24.1, 14.4; GCꢀMS (EI, QMS, m/z): 118.0, 161.1, 176.1, 271.1, 316.3;
HRMS (ESI): calcd for C20H29O3 , (M+H)+, 317.2111, found, 317.2115.
+
ethyl 2-methylene-7-(naphthalen-2-yl)-7-oxoheptanoate (3e). Procedure A: Colorless oil, 14.0
1
mg, 45% isolated yield. H NMR (400 MHz, CDCl3): δH 8.47 (s, 1H), 8.03 (d, J = 8.6 Hz, 1H),
7.96 (d, J = 8.0 Hz, 1H), 7.92ꢀ 7.85 (m, 2H), 7.57 (dt, J = 14.7, 6.7 Hz, 2H), 6.16 (s, 1H), 5.56 (s,
1H), 4.21 (q, J = 7.1 Hz, 2H), 3.13 (t, J = 7.3 Hz, 2H), 2.39 (t, J = 7.6 Hz, 2H), 1.90ꢀ1.79 (m, 2H),
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1.64 (dt, J = 15.2, 7.5 Hz, 2H), 1.30 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3): δC 200.3,
167.4, 140.7, 135.7, 134.4, 132.7, 129.8, 129.7, 128.5, 128.5, 127.9, 126.9, 124.8, 124.0, 60.7,
38.5, 31.9, 28.2, 24.1, 14.3; GCꢀMS (EI, QMS, m/z): 127.0, 155.0, 170.0, 265.1, 310.2; HRMS
(ESI): calcd for C20H22O3Na+, (M+H)+, 333.1461, found, 333.1462.
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ethyl 2-methylene-7-oxo-7-(phenanthren-9-yl)heptanoate (3f). Procedure A: colorless oil, 14.0
mg, 39% isolated yield. 1H NMR (600 MHz, CDCl3): δH 8.72 (d, J = 8.2 Hz, 1H), 8.68 (d, J = 8.5
Hz, 1H), 8.50 (d, J = 8.2 Hz, 1H), 8.09 (s, 1H), 7.95 (d, J = 7.8 Hz, 1H), 7.74 (t, J = 7.6 Hz, 1H),
7.69 (d, J = 8.0 Hz, 1H), 7.65 (t, J = 7.3 Hz, 2H), 6.16 (s, 1H), 5.56 (s, 1H), 4.20 (q, J = 7.1 Hz,
2H), 3.16 (t, J = 7.3 Hz, 2H), 2.39 (t, J = 7.4 Hz, 2H), 1.95ꢀ1.79 (m, 2H), 1.65 (dd, J = 15.1, 7.6
Hz, 2H), 1.29 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3): δC 204.9, 167.3, 140.5, 135.6,
131.7, 130.8, 130.1, 129.7, 128.9, 128.7, 128.4, 127.5, 127.1, 126.5, 124.7, 122.9, 122.7, 60.7,
42.1, 31.8, 28.1, 24.2, 14.2; GCꢀMS (EI, QMS, m/z): 151.1, 177.1, 205.1, 220.1, 360.2; HRMS
+
(ESI): calcd for C24H25O3 , (M+H)+, 361.1798, found, 361.1794.
ethyl 7-(benzofuran-2-yl)-2-methylene-7-oxoheptanoate (3g). Procedure A: yellow solid, 21.0
1
mg, 70% isolated yield. H NMR (400 MHz, CDCl3): δH 7.70 (d, J = 7.8 Hz, 1H), 7.57 (dd, J =
8.4, 0.6 Hz, 1H), 7.52ꢀ7.42 (m, 2H), 7.35ꢀ7.28 (m, 1H), 6.15 (s, 1H), 5.54 (d, J = 1.3 Hz, 1H),
4.20 (q, J = 7.1 Hz, 2H), 2.98 (t, J = 7.4 Hz, 2H), 2.37 (t, J = 7.5 Hz, 2H), 1.81 (dt, J = 15.1, 7.5
Hz, 2H), 1.64ꢀ1.54 (m, 2H), 1.29 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): δC 191.5,
167.3, 155.7, 152.7, 140.5, 128.3, 127.2, 124.8, 124.0, 123.4, 112.7, 112.6, 60.7, 38.8, 31.7, 28.1,
23.8, 14.3; GCꢀMS (EI, QMS, m/z): 145.0, 160.0, 226.1, 282.1, 300.1; HRMS (ESI): calcd for
+
C18H21O4 , (M+H)+, 301.1434, found, 301.1444.
ethyl 7-(benzo[b]thiophen-2-yl)-2-methylene-7-oxoheptanoate (3h). Procedure A: White solid,
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21.2 mg, 67% isolated yield. 1H NMR (400 MHz, CDCl3): δH 7.95 (s, 1H), 7.87 (t, J = 8.4 Hz, 2H),
7.42 (dtd, J = 14.8, 7.2, 1.2 Hz, 2H), 6.15 (s, 1H), 5.55 (d, J = 1.3 Hz, 1H), 4.20 (q, J = 7.1 Hz,
2H), 3.02 (t, J = 7.4 Hz, 2H), 2.37 (t, J = 7.5 Hz, 2H), 1.82 (dt, J = 15.1, 7.5 Hz, 2H), 1.65ꢀ1.54 (m,
2H), 1.29 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): δC 199.4, 168.6, 163.4, 139.8, 130.5,
130.4, 127.7, 113.8, 60.8, 55.5, 47.7, 45.9, 43.4, 40.7, 36.5, 32.2, 28.0, 21.6, 20.0, 19.9, 14.2;
GCꢀMS (EI, QMS, m/z): 161.0, 176.0, 242.0, 298.1, 316.1; HRMS (ESI): calcd for C18H21O3S+,
(M+H)+, 317.1206, found, 317.1201.
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ethyl 7-(1-methyl-1H-indol-2-yl)-2-methylene-7-oxoheptanoate (3i). Procedure A: colorless oil,
22.2 mg, yield 71%. 1H NMR (600 MHz, CDCl3): δH 7.69 (d, J = 8.0 Hz, 1H), 7.38 (s, 2H), 7.30
(s, 1H), 7.19ꢀ7.11 (m, 1H), 6.15 (s, 1H), 5.55 (s, 1H), 4.21 (q, J = 7.0 Hz, 2H), 4.08 (s, 3H), 2.99 (t,
J = 7.4 Hz, 2H), 2.37 (t, J = 7.5 Hz, 2H), 1.85ꢀ1.75 (m, 2H), 1.64ꢀ1.56 (m, 2H), 1.30 (t, J = 7.1 Hz,
3H); 13C NMR (151 MHz, CDCl3): δC 194.5, 167.4, 140.7, 140.2, 134.9, 126.0, 125.9, 124.8,
123.0, 120.8, 111.3, 110.5, 60.8, 39.8, 32.4, 31.9, 28.3, 24.8, 14.4; GCꢀMS (EI, QMS, m/z): 158.1,
173.1, 268.1, 295.1, 313.2; HRMS (ESI): calcd for C19H24O3N+, (M+H)+, 314.1751, found,
314.1745.
ethyl 5-(benzyloxy)-7-(4-methoxyphenyl)-2-methylene-7-oxoheptanoate (3j). Procedure A:
1
colorless oil, 26.1 mg, yield 66%. H NMR (600 MHz, CDCl3): δH 7.95 (d, J = 8.1 Hz, 2H),
7.34ꢀ7.23 (m, 5H), 6.93 (d, J = 8.1 Hz, 2H), 6.15 (s, 1H), 5.52 (s, 1H), 4.53 (s, 1H), 4.28ꢀ 4.16 (m,
3H), 3.87 (s, 3H), 3.37 (dd, J = 16.0, 6.5 Hz, 1H), 2.98 (dd, J = 16.0, 5.5 Hz, 1H), 2.54ꢀ2.39 (m,
2H), 1.82 (ddd, J = 16.3, 10.2, 6.0 Hz, 2H), 1.29 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3):
δC 197.4, 167.3, 163.7, 140.6, 138.6, 130.7, 130.5, 128.4, 127.9, 127.7, 124.8, 113.9, 75.6, 71.9,
60.8, 55.6, 43.4, 33.7, 27.8, 14.3; GCꢀMS (EI, QMS, m/z): 77.1, 135.1, 216.1, 305.1, 396.1;
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HRMS (ESI): calcd for C24H29O5 , (M+Na)+, 397.2010, found,397.2013.
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1-ethyl 6-methyl 5-(2-(4-methoxyphenyl)-2-oxoethyl)-2-methylenehexanedioate
(3k).
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Procedure A: colorless oil, 30.0 mg, 86% isolated yield containing 8% of 2a. 1H NMR (400 MHz,
CDCl3): δH 7.94 (d, J = 8.9 Hz, 2H), 6.93 (d, J = 8.9 Hz, 2H), 6.18 (s, 1H), 5.58 (s, 1H), 4.20 (q, J
= 7.1 Hz, 2H), 3.87 (s, 3H), 3.70 (s, 3H), 3.48ꢀ3.40 (m, 1H), 3.06 (dt, J = 12.8, 5.7 Hz, 2H), 2.37 (t,
J = 7.9 Hz, 2H), 1.93ꢀ1.73 (m, 2H), 1.30 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3): δC
196.6, 176.0, 167.1, 163.7, 139.9, 130.5, 129.8, 125.5, 113.9, 60.9, 55.6, 52.0, 40.1, 40.0, 31.0,
29.6, 14.3; GCꢀMS (EI, QMS, m/z): 135.0, 150.0, 303.1, 317.2, 348.2; HRMS (ESI): calcd for
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C19H24NaO6 , (M+H)+, 371.1465, found, 371.1456.
ethyl 2-(((1S)-2-(2-(4-methoxyphenyl)-2-oxoethyl)cyclopent-3-en-1-yl)methyl)acrylate (3l).
Procedure A: colorless oil, 13.8 mg, 42% isolated yield. 1H NMR (400 MHz, CDCl3): δH 7.93 (d, J
= 8.9 Hz, 2H), 6.92 (d, J = 8.9 Hz, 2H), 6.15 (d, J = 1.4 Hz, 1H), 5.67 (s, 2H), 5.52 (d, J = 1.2 Hz,
1H), 4.20 (qd, J = 7.1, 1.2 Hz, 2H), 3.86 (s, 3H), 3.01 (dd, J = 13.8, 4.1 Hz, 1H), 2.98ꢀ2.83 (m,
2H), 2.53 (ddd, J = 21.6, 9.1, 6.0 Hz, 2H), 2.32 (dd, J = 14.0, 9.0 Hz, 1H), 2.22ꢀ2.11 (m, 1H),
2.06ꢀ1.95 (m, 1H), 1.29 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3): δc 198.3, 167.4, 163.5,
139.8, 133.7, 130.5, 130.4, 129.9, 125.8, 113.8, 60.8, 55.6, 47.6, 43.9, 42.4, 38.0, 37.9, 14.4;
+
GCꢀMS (EI, QMS, m/z): 135.0, 149.0, 167.0, 279.1, 328.2; HRMS (ESI): calcd for C20H25O4 ,
(M+H)+, 329.1747, found, 329.1749.
ethyl 6-(4-methoxyphenyl)-2-methylene-6-oxohexanoate (5a). Procedure A: Colorless oil, 14.6
mg, 53% isolated yield. 1H NMR (600 MHz, CDCl3): δH 7.93 (d, J = 8.6 Hz, 2H), 6.92 (d, J = 8.6
Hz, 2H), 6.17 (s, 1H), 5.56 (s, 1H), 4.19 (q, J = 7.1 Hz, 2H), 3.86 (s, 3H), 2.94 (t, J = 7.3 Hz, 2H),
2.40 (t, J = 7.5 Hz, 2H), 2.00ꢀ1.88 (m, 2H), 1.29 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3):
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δC 198.6, 167.3, 163.5, 140.4, 130.4, 130.2, 125.1, 113.8, 60.8, 55.6, 37.5, 31.4, 23.1, 14.3;
GCꢀMS (EI, QMS, m/z): 135.1, 150.1, 207.0, 231.1, 276.1; HRMS (ESI): calcd for C16H20O4Na+,
(M+Na)+, 299.1254, found, 299.1260.
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ethyl 8-(4-methoxyphenyl)-2-methylene-8-oxooctanoate (5b). Procedure A: yellow oil, 21.2 mg,
70% isolated yield. 1H NMR (600 MHz, CDCl3): δH 7.93 (d, J = 8.4 Hz, 1H), 6.92 (d, J = 8.4 Hz,
1H), 6.12 (s, 1H), 5.50 (s, 1H), 4.19 (q, J = 7.1 Hz, 1H), 3.85 (s, 2H), 2.90 (t, J = 7.4 Hz, 1H), 2.30
(t, J = 7.6 Hz, 1H), 1.80ꢀ1.69 (m, 1H), 1.78ꢀ1.70 (m, 1H), 1.51 (dt, J = 15.2, 7.6 Hz, 1H), 1.40 (dt,
J = 15.0, 7.7 Hz, 1H), 1.28 (t, J = 7.1 Hz, 1H); 13C NMR (151 MHz, CDCl3): δC 199.1, 167.4,
163.4, 141.0, 130.4, 130.2, 124.5, 113.8, 60.7, 55.5, 38.2, 31.8, 29.1, 28.4, 24.4, 14.3; GCꢀMS (EI,
QMS, m/z) : 135.0, 150.0, 230.1, 286.4, 304.1; HRMS (ESI): calcd for C18H24NaO4 , (M+Na)+,
+
327.1567, found, 327.1575.
ethyl 9-(4-methoxyphenyl)-2-methylene-9-oxononanoate (5c). Procedure A: colorless oil, 20.7
mg, 65% isolated yield. 1H NMR (400 MHz, CDCl3): δH 7.93 (d, J = 8.9 Hz, 2H), 6.92 (d, J = 8.9
Hz, 2H), 6.11 (d, J = 1.1 Hz, 1H), 5.49 (d, J = 1.4 Hz, 1H), 4.19 (q, J = 7.1 Hz, 2H), 3.86 (s, 3H),
2.89 (t, J = 7.4 Hz, 2H), 2.33ꢀ2.24 (t, 2H), 1.75ꢀ1.67 (m, 2H), 1.47 (dt, J = 14.7, 7.3 Hz, 2H), 1.38
(dt, J = 10.5, 3.5 Hz, 4H), 1.29 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3): δC 199.3, 167.5,
163.4, 141.1, 130.4, 130.3, 124.38, 113.8, 60.7, 55.6, 38.3, 31.9, 29.3, 29.2, 28.4, 24.6, 14.3;
+
GCꢀMS (EI, QMS, m/z): 135.1, 155.1, 254.1, 273.1, 318.2; HRMS (ESI): calcd for C19H27O4 ,
(M+H)+, 319.1904, found, 319.1906.
10-(4-methoxyphenyl)-2-methylene-10-oxodecanoate (5d). Procedure A: colorless oil, 27.2 mg,
82% isolated yield. 1H NMR (600 MHz, CDCl3): δH 7.92 (d, J = 8.1 Hz, 2H), 6.91 (d, J = 8.1 Hz,
2H), 6.10 (s, 1H), 5.48 (s, 1H), 4.18 (q, J = 7.0 Hz, 2H), 3.85 (s, 3H), 2.89 (t, J = 7.3 Hz, 2H), 2.27
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(t, J = 7.4 Hz, 2H), 1.73ꢀ1.68 (m, 2H), 1.50ꢀ1.40 (m, 2H), 1.34 (s, 6H), 1.28 (t, J = 7.1 Hz, 3H);
13C NMR (151 MHz, CDCl3): δC 199.3, 167.5, 163.4, 141.2, 130.4, 130.3, 124.3, 113.8, 60.6, 55.5,
38.4, 31.9, 29.4, 29.4, 29.2, 28.4, 24.7, 14.3; GCꢀMS (EI, QMS, m/z): 135.1, 150.1, 241.2.0, 287.1,
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332.3; HRMS (ESI): calcd for C20H29O4 , (M+H)+, 333.2060, found, 333.2062.
ethyl 11-(4-methoxyphenyl)-2-methylene-11-oxoundecanoate (5e). Procedure A: yellow oil,
21.8 mg, 63% isolated yield. 1H NMR (600 MHz, CDCl3): δH 7.94 (d, J = 8.8 Hz, 2H), 6.92 (d, J
= 8.8 Hz, 2H), 6.11 (s, 1H), 5.49 (s, 1H), 4.19 (q, J = 7.1 Hz, 2H), 3.86 (s, 3H), 2.90 (t, J = 7.4 Hz,
2H), 2.28 (t, J = 7.6 Hz, 2H), 1.75ꢀ1.65 (m, 2H), 1.44 (d, J = 6.4 Hz, 2H), 1.39ꢀ1.27 (m, 11H); 13
C
NMR (151 MHz, CDCl3): δC 199.4, 167.5, 163.4, 141.2, 130.4, 130.3, 124.3, 113.8, 60.6, 55.6,
38.4, 31.9, 29.5, 29.5, 29.4, 29.3, 28.5, 24.7, 14.3; GCꢀMS (EI, QMS, m/z): 135.0, 150.1, 163.0,
255.2, 346.2; HRMS (ESI): calcd for C21H30NaO4 , (M+Na)+, 369.2036, found, 369.2039.
+
ethyl 15-(4-methoxyphenyl)-2-methylene-15-oxopentadecanoate (5f). Procedure A: colorless
oil, 32.5 mg, 81% isolated yield. 1H NMR (600 MHz, CDCl3): δH 7.93 (d, J = 8.6 Hz, 2H), 6.91 (d,
J = 8.6 Hz, 2H), 6.10 (s, 1H), 5.49 (s, 1H), 4.18 (q, J = 7.1 Hz, 2H), 3.85 (s, 3H), 2.89 (t, J = 7.4
Hz, 2H), 2.27 (t, J = 7.6 Hz, 2H), 1.74ꢀ1.64 (m, 2H), 1.43 (dd, J = 14.3, 7.0 Hz, 2H), 1.38ꢀ1.18 (m,
20H); 13C NMR (151 MHz, CDCl3): δC 199.3, 167.5, 163.4, 141.2, 130.4, 130.3, 124.2, 113.7,
60.6, 55.5, 38.4, 31.9, 29.7, 29.7, 29.7, 29.6, 29.5, 29.5, 29.3, 28.5, 24.7, 14.3; GCꢀMS (EI, QMS,
m/z): 135.1, 150.1, 328.2, 384.3, 402.3; HRMS (ESI): calcd for C25H39O4 , (M+H)+, 403.2843,
+
found, 403.2847.
ethyl 5-(3-(4-methoxyphenyl)-3-oxopropoxy)-2-methylenepentanoate (5g). Procedure A:
1
colorless oil, 23.4 mg, 73% isolated yield containing 6% of 2a. H NMR (600 MHz, CDCl3): δH
7.96 (d, J = 8.4 Hz, 2H), 6.94 (d, J = 8.5 Hz, 2H), 6.14 (s, 1H), 5.52 (s, 1H), 4.20(q, 2H), 3.87 (s,
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3H), 3.84 (t, J = 6.6 Hz, 2H), 3.48 (t, J = 6.3 Hz, 2H), 3.20 (t, J = 6.6 Hz, 2H), 2.35 (t, J = 7.5 Hz,
2H), 1.77ꢀ1.70 (m, 2H), 1.29 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz, CDCl3): δC 197.1, 167.2,
163.5, 140.3, 130.5, 130.2, 129.1, 128.8, 124.8, 113.7, 70.3, 66.2, 60.6, 55.5, 38.5, 28.5, 28.3, 14.2;
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GCꢀMS (EI, QMS, m/z): 150.1, 163.1, 241.1, 287.1, 320.2; HRMS (ESI): calcd for C18H25O5 ,
(M+H)+, 321.1697, found, 321.1706.
ethyl 5-((ethoxycarbonyl)(3-(4-methoxyphenyl)-3-oxopropyl)amino)-2-methylenepentanoate
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(5h). Procedure A: colorless oil, 28.5 mg, 73% isolated yield. H NMR (400 MHz, CDCl3): δH
7.95 (s, 2H), 6.93 (d, J = 8.2 Hz, 2H), 6.16 (s, 1H), 5.54 (s, 1H), 4.20 (q, J = 7.1 Hz, 2H), 4.13 (q,
J = 7.0 Hz, 2H), 3.87 (s, 3H), 3.62 (t, J = 7.1 Hz, 2H), 3.37ꢀ3.09 (m, 4H), 2.29 (s, 2H), 1.73 (s,
2H), 1.34ꢀ1.18 (m, 6H); 13C NMR (151 MHz, CDCl3): δC 197.6, 167.0, 163.7, 140.0, 130.5, 130.4,
124.9, 124.7, 113.8, 61.2, 60.7, 55.5, 47.6, 43.8, 37.3, 29.1, 27.4, 14.7, 14.2; GCꢀMS (EI, QMS,
m/z): 135.1, 168.1, 241.2, 318.2, 391.3; HRMS (ESI): calcd for C21H30NO6 , (M+H)+, 392.2068,
+
found, 392.2061.
ethyl 2-(((3-(4-methoxyphenyl)-3-oxopropyl)thio)methyl)acrylate (5i). Procedure A: colorless
oil, 24.6 mg, 80% isolated yield. 1H NMR (400 MHz, CDCl3): δH 7.93 (d, J = 8.8 Hz, 2H), 6.94 (d,
J = 8.8 Hz, 2H), 6.22 (s, 1H), 5.71 (s, 1H), 4.24 (q, J = 7.1 Hz, 2H), 3.87 (s, 3H), 3.44 (s, 2H),
3.21 (t, J = 7.4 Hz, 2H), 2.86 (t, J = 7.4 Hz, 2H), 1.31 (t, J = 7.1 Hz, 3H); 13C NMR (151 MHz,
CDCl3): δC 196.9, 166.3, 163.8, 137.2, 130.5, 129.8, 126.1, 113.9, 61.2, 55.6, 38.4, 33.4, 26.2,
14.3; GCꢀMS (EI, QMS, m/z): 135.0, 163.0, 195.0, 275.1, 308.1; HRMS (ESI): calcd for
C16H21O4S+, (M+H)+, 309.1155, found, 309.1148.
ethyl (R)-8-(4-methoxyphenyl)-4,6,6-trimethyl-2-methylene-8-oxooctanoate (5j). Procedure A:
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colorless oil, 27.0 mg, 78% isolated yield. H NMR (400 MHz, CDCl3): δH 7.92 (d, J = 8.9 Hz,
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2H), 6.91 (d, J = 8.9 Hz, 2H), 6.15 (d, J = 1.7 Hz, 1H), 5.46 (s, 1H), 4.17 (qd, J = 7.1, 0.7 Hz, 2H),
3.85 (s, 3H), 2.82 (q, J = 14.5 Hz, 2H), 2.36 (dd, J = 13.3, 5.4 Hz, 1H), 2.04 (dd, J = 13.4, 8.5 Hz,
1H), 1.85ꢀ1.74 (m, 1H), 1.43 (dd, J = 14.1, 3.9 Hz, 1H), 1.34ꢀ1.24 (m, 4H), 1.03 (d, J = 4.3 Hz,
6H), 0.89 (d, J = 6.7 Hz, 3H); 13C NMR (151 MHz, CDCl3): δC 199.1, 167.5, 163.3, 139.9, 131.9,
130.6, 126.4, 113.7, 60.7, 55.5, 49.6, 48.5, 42.3, 34.7, 28.1, 27.9, 22.5, 14.4; GCꢀMS (EI, QMS,
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m/z): 135.0, 150.1, 191.1, 263.1, 346.2; HRMS (ESI): calcd for C21H30NaO4 , (M+Na)+, 369.2036,
+
found, 369.2040.
ethyl (4R)-4-isopropyl-9-(4-methoxyphenyl)-7-methyl-2-methylene-9-oxononanoate (5k).
Procedure A: colorless oil, 20.9 mg, 56% isolated yield. 1H NMR (400 MHz, CDCl3): δH 7.92 (d, J
= 8.5 Hz, 2H), 6.93 (d, J = 8.5 Hz, 2H), 6.14 (s, 1H), 5.46 (d, J = 3.8 Hz, 1H), 4.18 (q, J = 7.1 Hz,
2H), 3.86 (s, 3H), 2.94ꢀ2.80 (m, 1H), 2.68 (dd, J = 15.5, 8.1 Hz, 1H), 2.39ꢀ2.25 (m, 1H), 2.19ꢀ2.02
(m, 2H), 1.81ꢀ1.65 (m, 1H), 1.43ꢀ1.33 (m, 2H), 1.31ꢀ1.10 (m, 6H), 0.92 (d, J = 6.6 Hz, 3H),
0.88ꢀ0.78 (m, 6H); 13C NMR (151 MHz, CDCl3): δ 199.2, 167.6, 163.4 , 140.5, 130.7 (d, J = 3.2
Hz), 125.8, 113.8 , 60.7, 55.6, 45.8(d, J = 8.2 Hz), 42.5 (d, J = 16.4 Hz), 35.0 (d, J = 8.1 Hz), 33.5
(d, J = 17.3 Hz), 30.6 (d, J = 3.0 Hz), 28.6 (d, J = 24.3 Hz), 27.2 (d, J = 18.3 Hz), 20.2 (d, J = 3.0
Hz), 19.1 (d, J = 15.0 Hz), 18.7 (d, J = 8.5 Hz), 14.3; GCꢀMS (EI, QMS, m/z): 135.0, 150.1, 207.0,
+
346.1, 374.2; HRMS (ESI): calcd for C23H35O4 , (M+H)+, 375.2530, found, 375.2520.
ethyl-2-(((1R,3S,3aS,6aR)-3-(2-(4-methoxyphenyl)-2-oxoethyl)octahydropentalen-1-yl)methy
1
l)acrylate (5l). Procedure A: colorless oil, 17.0 mg, 46% isolated yield. H NMR (600 MHz,
CDCl3): δH 7.93 (d, J = 8.3 Hz, 2H), 6.93 (d, J = 8.5 Hz, 2H), 6.09 (s, 1H), 5.49 (s, 1H), 4.25ꢀ4.12
(m, 2H), 3.87 (s, 3H), 3.02 (dd, J = 15.0, 4.8 Hz, 1H), 2.87 (dd, J = 14.8, 8.3 Hz, 1H), 2.47 (dd, J
= 13.6, 5.6 Hz, 1H), 2.22 (dd, J = 13.5, 8.6 Hz, 1H), 2.13 (m, J = 6.8 Hz, 1H), 2.04 (dd, J = 15.4,
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