Enabling the development of N-Heterocyclic Carbene (NHC) catalyzed reactions: Practical methods for the preparation of 1-acyl-2-alkylcycloalkenes from cycloalkanones

Article abstract of DOI:10.1071/CH11183

The synthesis of 1-acyl-2-alkylcycloalkenes from a variety of cycloalkanones has been achieved via either-keto enol phosphates or-bromoenones. Both methods exploit simple and readily scalable transformations allowing the preparation of the desired compoun

Full text of DOI:10.1071/CH11183

RESEARCH FRONT
Full Paper
CSIRO PUBLISHING
Aust. J. Chem. 2011, 64, 1148–1157
www.publish.csiro.au/journals/ajc
Enabling the Development of N-Heterocyclic Carbene
(NHC) Catalyzed Reactions: Practical Methods
for the Preparation of 1-Acyl-2-Alkylcycloalkenes
from Cycloalkanones
A
A
A
A B
,
Sarah J. Ryan, Lisa Candish, Iva´n Mart´ınez, and David W. Lupton
A
School of Chemistry, Monash University, Clayton 3800, Victoria, Australia.
B
Corresponding author. Email: david.lupton@monash.edu
The synthesis of 1-acyl-2-alkylcycloalkenes from a variety of cycloalkanones has been achieved via either b-keto enol
phosphates or b-bromoenones. Both methods exploit simple and readily scalable transformations allowing the preparation
of the desired compounds to be achieved in three, or four steps, respectively. The utility of these strategies has been
examined, resulting in the preparation of 17 disubstituted cycloalkenes.
Manuscript received: 5 May 2011.
Manuscript accepted: 10 June 2011.
development of [4 þ 2] cycloadditions (Scheme 2).[2c] In this
transformation NHC-mediated substitution of acyl fluoride 4
triggers desilylation of TMS dienol ether 3 to provide the ion
pair III. These undergo a highly endo selective coupling to
presumably provide b-lactone IV, which then decarboxylates to
give the observed cyclohexadienes 5. In addition to providing an
additional example of the use of NHCs to catalyze reactions
without polarity inversion, this transformation provides a pow-
erful method to valuable cyclohexadienes.
To develop the [4 þ 2] cycloaddition, access to the
starting materials 3 and 4 was required. Acid fluorides 4
are available in one step from the corresponding acid,[4] and
the TMS enol ethers 3 are accessible by g-deprotonation of
the 1-acyl-2-alkylcycloalkenes (i.e. 6, Scheme 3).[2c,5] Un-
fortunately, we were surprised to find limited reports on the
synthesis of the later compounds.[6,7] Furthermore, these
methods were plagued by combinations of poor yield,
restricted scope, and the requirement of nontrivial starting
materials or reagents.[7] To allow a meaningful examination
of the NHC-catalyzed [4 þ 2] cycloaddition, scalable meth-
ods for the preparation of 1-acyl-2-alkylcycloalkenes (i.e. 6)
were required. Herein, we report our studies on this topic
with two strategies that allow the preparation of a broad
range of 1-acyl-2-alkylcycloalkenes 6. Both methods exploit
cheap and readily available reagents, making them achiev-
able in a variety of laboratories, across a range of scales.
Introduction
N-Heterocyclic carbenes (NHCs) have great utility, with roles
at the frontiers of transition metal and organo- catalysis.[1]
In the later field, NHC-mediated carbonyl umpolung has a long
history.[1a,b] More recently rich and diverse reactivity has been
accessed by combining both normal and reverse polarity events
in a single reaction cascade.[1b–g] Our studies have focussed on
the use of NHCs as Lewis bases capable of catalyzing trans-
formations without carbonyl umpolung.[2] In 2009 we realized
this concept, demonstrating that a,b-unsaturated enol esters 1
are rearranged by diaryl imidazolium-derived NHCs to provide
dihydropyranones 2 (Scheme 1).[2a] Mechanistically, this
isomerization likely proceeds via formation of hemiacetal I,
followed by either a 3,3-sigmatropic rearrangement, or frag-
mentation to the a,b-unsaturated acyl azolium[3] enolate ion
pair II followed by conjugate addition. Last year Bode reported
a related transformation and, from kinetic analysis, postulated a
mechanism involving a 3,3-sigmatropic rearrangement.[3l,o]
While both may proceed via a common pathway, significant
differences regarding the reaction conditions raise the possi-
bility that distinct mechanisms may be operative. Although
the mechanism of this transformation is not yet clear, its utility
has been examined through the total synthesis of 7-
deoxyloganin.[2b]
Earlier this year we reported the NHC-triggered formation of
acyl azoliums and dienolates in studies focussed on the
R1
10–20 mol % cat A,
R1
20–40 mol % KOtBu,
R1
O
R1
R
Ar
Cl
N
O
Ar
O
Ar
toluene, Δ, 16h
O
N
O
O
N
N
N
yield 45–92 %
R
Ar
R
O
O
R
N
cat. A
1
Ar
I
II
2
Ar
Scheme 1. NHC catalyzed pyranone synthesis.[2a]
Ó CSIRO 2011
10.1071/CH11183
0004-9425/11/081148

RESEARCH FRONT
Enabling Discoveries in NHC Catalysis: Assembly of 1-acyl-2-alkylcycloalkenes
1149
Results and Discussion
The regioisomeric composition of the enol phosphate products
was at worst 4:1 (Table 1, entries 1, 2 and 7), with most examples
occurring with $ 8:1 selectivity for the desired enol phosphate.
Substituted aromatic starting materials were tolerated, with
electron poor aroyl-cyclohexanones affording enol phosphates
7c and d in good yield (Table 1, entries 3–5). Similarly,
cinnamoylcyclohexanone 8e and furoyl-cyclohexenone 8f were
compatible with the reaction conditions (Table 1, entries 5 and 6).
Finally, incorporation of additional degrees of unsaturation
and the use of bicyclic substrates proved suitable, allowing enol
phosphates 7 g and h to be prepared in good yields with excellent
regioselectivity (Table 1, entries 7 and 8). The formation of the
b-keto enol phosphates 7 was remarkably reliable, performing
well over a range of scales. This transformation was regularly
performed on 0.05 mol of b-diketones 8 without modification to
the reaction conditions.
The enol phosphates were next subjected to dialkylcuprate
coupling using conditions developed by Weiler.[8] While
LiMe2Cu provided products 6a, c, d and f-h in good yields
(Table 1, entries 1, 3, 4 and 6–8), when cinnamoyl phosphate 7e
was reacted a mixture of products resulted (Table 1, entry 5),
presumably due to undesired conjugate addition pathways. In
addition, LiBu2Cu could be used to install a butyl side chain,
albeit in lower yields (Table 1, entry 2).
Method 1: Preparation of 1-acyl-2-alkylcycloalkenes 6 via
enol phosphates 7
While dialkylcuprate coupling of enol phosphates derived
from b-ketoesters and symmetrical b-diketones was first
reported in 1979,[8a] this transformation is yet to be applied to
phosphates derived from unsymmetrical b-diketones. This
situation presumably arises due to difficulties, or perceived
difficulties, associated with regioselective b-keto enol phos-
phate formation.[9] If regioselectivity could be achieved, then a
viable approach to 1-acyl-2-alkylcycloalkenes 6, from the
corresponding b-keto enol phosphates (i.e. 7a) should be
possible. To explore this strategy the formation of phosphate
7a (and the undesired 7a9) from benzoyl cyclohexanone 8a
was examined. It was hypothesized that generation of 7a
should be favoured over 7a9 due to buttressing of the phosphate
residue with the carbonyl group in the latter compound. When
b-diketone 8a was subjected to conditions developed for the
conversion of b-ketoesters,[8] we were pleased to discover that
7a was the major product. Unfortunately, this effect was only
modest, with products 7a and 7a9 generated in a 3:2 ratio
(Scheme 4). By extending the equilibration time before addi-
tion of phosphoryl chloride enol phosphate, 7a now formed in
an improved 4:1 ratio, and in an isolated yield of 72 % (Table 1,
entry 1). Subsequent conversion of phosphate 7a to 1-acyl-2-
alkylcycloalkenes 6a was achieved with LiMe2Cu in excellent
yield (Table 1, entry 1),[8] demonstrating the viability of this
approach.
Although this strategy allows the conversion of cycloalk-
anones to the desired 1-acyl-2-alkylcycloalkenes, it suffers from
limitations. Most significantly the incorporation of the butyl
group could only be achieved in low yield. Whether this result
was indicative of restricted reactivity with non-methyl alkyl
lithiums was not examined further. This was due to restricted
availability of alkyl lithium reagents compared with the
Grignard reagents, materials that served as the key coupling
partner in the second approach.
To explore the generality of this reaction sequence, a range of
b-diketones 8 were required. In our hands, the acylation of
the corresponding ketone[10a] or enamine[10b] proved convenient
for their preparation. Exploiting the optimized conditions, a
variety of enol phosphates 7 were prepared (Table 1, entries 1–8).
R2
R2
R3
iPr
10 mol % cat. B, THF,
Ϫ78→Ϫ10 ЊC, 1h
3
R
N
O
N
TMSO
H3C
drϾ20:1
yield 56–98 %
iPr
F
4
R1
R1
CH3
3
5
cat. B
ϪTMSF
ϪCO2
R2
R3
R2
R3
endo [4 ϩ 2] cycloaddition
β-lactonisation
O
N
O
iPr
iPr
R1
N
R1
IV
O
O
III
H3C
CH3
Scheme 2. NHC catalyzed [4 þ 2] cycloaddition/decarboxylation.[2c]
Reported herein
R2
R2
via β-ketoenol
phosphates
LDA, TMSCl,
THF, Ϫ78 ЊC, 1h
O
O
or
TMSO
β−bromoenones
R1
R1
3
6
Scheme 3. Strategy for the synthesis of 1-acyl-2-alkylcycloalkenes 6.

RESEARCH FRONT
1150
S. J. Ryan et al.
O
H3C
O
(EtO)2PO
(ii)
O
O
O
(i)
7a
Ph 6a
Ph
O
O
Ph 8a
(EtO)2PO
Ph
7aЈ
Scheme 4. Reagents and Conditions: (i) NaH, Et2O, 0 - 18 8C, 1.5 h, then (EtO)2 PO(Cl), 18 8C, 2 h. (ii) LiMe2Cu, Et2O, –78 8C, 1 h
Method 2: Preparation of 1-acyl-2-alkylcycloalkenes 6 via
b-bromo enones 9
phosphates from non-symmetrical b-diketones. While this
strategy was useful, it was less successful in delivering non-
methyl b-alkylated compounds. Our second strategy addressed
this limitation through use of an iron-catalyzed cross coupling
between b-bromoenones and a diverse range of Grignard
reagents. Remarkably, this reaction provided the desired pro-
ducts without any direct addition to the carbonyl group in all but
one case. Combined, these two methods provided access to 17
cycloalkenes in good to excellent yields. In addition to enabling
our studies on the NHC-catalyzed [4 þ 2] cycloaddition, these
procedures provide a valuable resource for the synthesis of
1-acyl-2-alkylcycloalkenes (i.e. 6).
Since the pioneering work of Kochi,[11a] iron catalyzed coupling
of vinyl bromides with alkylmagnesium halides has seen
extensive investigation.[11] The use of inexpensive iron catalysts
in association with a range of Grignard reagents, makes this an
attractive strategy for the preparation of substituted alkenes.[11,12]
In addition, cross-couplings proceed with exquisite chemoselec-
tivity, for example certain ketones and esters are able to couple
without any direct carbonyl addition.[11f] To test whether iron
catalyzed cross-coupling could furnish 1-acyl-2-alkylcycloalk-
enes (i.e. 6) we chose to target bromide 9a. When the coupling
reaction was attempted, the desired methylketone 6a was formed
in 99% yield without any addition into the ketone functionality.
To explore the breadth of this reaction, a variety of b-
bromoenones 9 were required. In all cases they were prepared
from the bromoaldehydes 10, themselves accessed via halofor-
mylation of the corresponding cycloalkanone.[13] This was
followed by treatment with an appropriate Grignard reagent
and oxidation of the resulting alcohol with PCC, to give 9
(Table 2). When b-bromoenone 9a was subjected to iron-
catalyzed coupling with the methyl, ethyl, propyl and butenyl
Grignard reagents, ketones 6a, i, j and k formed in good yields
(Table 2, entry 1–4). Unfortunately, when the cross-coupling
was attempted with allyl magnesium bromide addition into the
ketone gave the allylic alcohol as the only isolable product
(Table 1, entry 5). Attention was next turned to variations in the
b-bromoenone 9. Those containing alkyl or substituted aromatic
substituents proved successful when reacted with methyl mag-
nesium bromide, providing ketones 6l-n (Table 2, entries 6–8).
In addition the ring expanded bromide 9o and bicyclic bromides
9p and q reacted smoothly (Table 2, entries 9–11).
Experimental Section
Unless otherwise specified, proton (1H) and carbon (13C) NMR
spectra were recorded in CDCl3 on a Varian Mercury 300
spectrometer operating at 300 MHz for proton and 75 MHz for
carbon nuclei or a Varian DRX 500 spectrometer operating at
500 MHz for proton and 125 MHz for carbon. Signals arising
from the residual protio-forms of the solvent were used as the
internal standard. Infrared spectra (nmax) were recorded on a
Perkin–Elmer RXI FTIR Spectrometer. Samples were analyzed
as thin films on NaCl plates. High resolution mass spectra
(HRMS) (ESI) were recorded on a Bruker BioApex 47e FTMS
fitted with an analytical electrospray source using NaI for ac-
curate mass calibration. HRMS (EI) were recorder on an Agilent
7890A GC, Waters GCT Premier TOF-MS with an ion source
temperature of 2008C and electron impact energy (70 eV). Flash
column chromatography was performed on silica gel (Davisil
LC60A, 40–63 mm silica media) using compressed air or nitro-
gen. Thin-layer chromatography (TLC) was performed using
aluminium or plastic backed plates coated with 0.2 mm silica
(Merck, DC-Platten, Kieselgel; 60 F254 plates). Eluted plates
were visualized using a 254-nm UV lamp and by treatment with
a suitable stain followed by heating.
As with the transformations described in method 1, the cross-
coupling could be performed on a range of scales, and was
regularly conducted on 20 mmol of b-bromenone 9 without
modification of the reaction conditions.
Starting materials and reagents were purchased from Sigma-
Aldrich and were used as supplied or, in the case of some liquids,
distilled. Tetrahydrofuran (THF) and diethyl ether were distilled
from sodium benzophenone ketyl. Concentration under reduced
pressure was performed on a rotary evaporator with the water
bath temperature not exceeding 408C. b-Diketones 8 were
prepared using reported procedures.[10]
Conclusions
The development of new chemical transformations requires
simple procedures that provide rapid access to substrates.
During the course of studies into a novel NHC-catalyzed [4 þ 2]
cycloaddition, we required access to a range of 1-acyl-2-
alkylcycloalkenes 6. Herein, we report the development of
approaches for the preparation of these materials from cyclo-
alkanones via either the b-keto enol phosphate 7, in 3 steps, or
the b-bromo enone 9, in 4 steps. The first strategy was possible
due to the preference for formation of endocyclic enol
Procedure for the synthesis of b-keto enol phosphates 7
Using a modification to the procedure reported by Weiler,[8]
b-diketones 8 (12.0 mmol) in diethyl ether (2 mL) were added to
a suspension of NaH (528 mg of a 60 % suspension in mineral
oil, 13.2 mmol) in diethyl ether (20 mL) at 08C. The mixture was

RESEARCH FRONT
Enabling Discoveries in NHC Catalysis: Assembly of 1-acyl-2-alkylcycloalkenes
1151
Table 1. Scope of 1-acyl-2-alkylcycloalkenes 6 synthesis via b-keto enol phosphates 7
(i) NaH, Et2O,
1.5h then
(EtO)2PO(Cl), 2h
O
(ii) Li(R2)2Cu,
Et2O, Ϫ78 ЊC, 1 h
R2
O
(EtO)2PO
O
O
O
R1
R1
R1
Yield 7b
8
7
6
a
Entry
Starting Material 8
Ratio 7:70
R2
Productc
Yield 6b
O
O
O
1
4:1
72 %
Me
94 %
6a
8a
Ph
Ph
2
‘
4:1
72 %
Bu
25 %
O
6b
Ph
O
O
O
3
1:0
53 %
Me
73 %
6c
8c
8d
Br
Br
O
O
O
6d
4
1:0
42 %
Me
55 %
Br
Br
O
O
5
9:1
74 %
Me
–
–
8e
Ph
O
O
O
6
8:1
65 %
Me
76 %
6f
8f
O
O
O
O
O
O
7
8
4:1
9:1
62 %
57 %
Me
Me
81 %
83 %
6g
8g
Ph
Ph
O
O
6h
Ph
8h
Ph
aRatio of 7:79 was determined by analysis of the crude 1H NMR spectrum. bIsolated yield following flash column chromatography. cLithium dialkylcuprate
generated according to Weiler.[8]

RESEARCH FRONT
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S. J. Ryan et al.
Table 2. Scope of 1-acyl-2-alkylcycloalkenes 6 synthesis via b-bromo enones 9
(i) R1MgX, THF,
Ϫ78ЊC, 1 h
(ii) PCC, CH2Cl2,
18ЊC, 6 h
(iii) 10 mol %
R2
Fe(acac)3, R2MgX,
NMP, THF, 0 ЊC, 1 h
Br
Br
O
O
O
R1
Yield 9a,b
9
R1
6
10
Entry
SM 10
R1
Ph
R2
Product
Yield 6a
99 %
Br
O
O
O
1
86 %
Me
6a
6i
Ph
Ph
10a
2
‘
‘
‘
Et
99 %
3
‘
‘
‘
Pr
31 %
O
O
6j
Ph
4
‘
‘
‘
But-en-yl
77 %
6k
Ph
Br
HO
c
5
‘
‘
‘
Allyl
-
Ph
O
O
O
6
7
‘
‘
Me
54 %
60 %
Me
Me
52 %
74 %
6l
CH3
iPr
6m
6n
8
‘
4-OMePh
67 %
Me
82 %
OMe
(Continued)

RESEARCH FRONT
Enabling Discoveries in NHC Catalysis: Assembly of 1-acyl-2-alkylcycloalkenes
1153
Table 2. (Continued)
Entry
SM 10
R1
Ph
Yield 9a,b
R2
Product
Yield 6a
81 %
Br
O
O
9
62 %
Me
6o
Ph
10o
Br
O
O
10
Ph
71 %
Me
77 %
Ph
10p
6p
O
11
‘
iPr
47 %
Me
68 %
6q
aIsolated yield following flash column chromatography. bYield was calculated for the two steps. cIdentified in variable yields as the only product.
allowed to warm to room temperature, and stirring continued for
a further hour. After this time, phosphoryl chloride (2.28 g,
13.2 mmol) was slowly added and the mixture stirred for an
additional 2 h. The suspension was quenched with NH4Cl (5 mL
of a saturated aqueous solution) and extracted with diethyl ether
(3 ꢀ 10 mL), the combined organic layers were dried (MgSO4),
filtered, and the volatiles evaporated. The crude residue was
purified by flash column chromatography (4:1, v/v EtOAc/
hexanes) to provide the title compound b-keto enol phosphates 7
along with the regioisomeric product. Yields and ratios of 7:79
are reported in Table 1.
2-Benzoylcyclohex-1-en-1-yl diethyl phosphate (7a). Clear
colourless oil. Rf 0.3 (4:1, v/v EtOAc/hexanes). nmax/cmꢁ1
3490, 2985, 1660, 1449, 1283, 1132, 1034. dH (300 MHz,
CDCl3) 7.93–7.90 (m, 2H), 7.58–7.51 (m, 1H), 7.47–7.42
(m, 2H), 3.79–3.65 (m, 4H), 2.60–2.52 (m, 2H), 2.41–2.36
(m, 2H), 1.90–1.81 (m, 2H), 1.76–1.68 (m, 2H), 1.11 (dt, J
6.6, 1.2, 6H). dC (75 MHz, CDCl3) 196.8, 147.2 (d, J 7.1), 136.9,
132.8, 129.1, 128.2, 121.9 (d, J 8.6), 63.9 (d, J 6.3), 27.5, 26.2,
22.4, 21.4, 15.6 (d, J 6.8). m/z (HR-ESI) Found (MþH)þ
339.1358, C17H23O5P requires (MþH)þ 339.1361.
129.5, 127.1, 121.8 (d, J 8.6), 119.2, 64.1 (d, J 6.2), 28.5, 25.2,
22.2, 21.5, 15.9 (d, J 7.1). m/z (HR-ESI) Found (MþH)þ
417.0464, C17H22BrO5P requires (MþH)þ 417.0467.
2-(3-Bromobenzoyl)cyclohex-1-en-yl diethyl phosphate (7d).
Prepared using the procedure described for compound 7a. Clear
colourless oil. Rf 0.2 (3:2, v/v EtOAc/hexanes). nmax/cmꢁ1
3501, 2939, 1667, 1567, 1361, 1285, 1032. dH (300 MHz,
CDCl3) 7.99 (t, J 1.8, 1H), 7.80 (dt, J 7.8, 1.8, 1H), 7.65 (dq, J
7.8, 0.9, 1H), 7.33 (t, J 7.8, 1H), 3.83–3.71 (m, 4H), 2.60–2.52
(m, 2H), 2.41–2.36 (m, 2H), 1.88–1.83 (m, 2H), 1.75–1.68
(m,2H), 1.15 (td, J 6.9, 0.9, 6H). dC (75 MHz, CDCl3) 195.6,
148.6 (d, J 7.1), 139.1, 135.2, 131.6, 129.8, 127.7, 122.3, 121.4
(d, J 8.3), 63.9 (d, J 6.6), 27.6, 26.0, 22.3, 21.3, 15.6 (d, J 7.1).
m/z (HR-ESI) Found (MþH)þ 417.0462, C17H22BrO5P requires
(MþH)þ 417.0467.
(E) 2-Cinnamoylcyclohex-1-en-yl diethyl phosphate (7e).
Prepared using the procedure described for compound 7a. Clear
colourless oil. Rf 0.2 (3:2, v/v EtOAc/hexanes). nmax/cmꢁ1
2939, 1647, 1598, 1367, 1285, 1032. dH (300 MHz, CDCl3)
7.59–7.54 (m, 3H), 7.35–7.33 (m, 3H), 7.13 (d, J 16.2, 1H),
4.09–3.97 (m, 4H), 2.54–2.49 (m, 2H), 2.37–2.34 (m, 2H), 1.77–
1.72 (m, 2H), 1.63–1.60 (m, 2H), 1.80 (dt, J 6.0, 0.9, 6H). dC
(75 MHz, CDCl3) 193.2, 150.8 (d, J 7.4), 142.6, 134.9, 130.1,
128.7, 128.2, 126.6, 123.8 (d, J 8.6), 64.4 (d, J 6.0), 28.4, 25.4,
22.5, 21.5, 15.8 (d, J 6.9). m/z (HR-ESI) Found (MþH)þ
365.1516, C19H25O5P requires (MþH)þ 365.1518.
(Z)-diethyl ((2-oxocyclohexylidene)(phenyl)methyl) phos-
phate (7a9). Clear colourless oil. Rf 0.2 (4:1, v/v EtOAc/
hexanes). nmax/cmꢁ1 3490, 2932, 1699, 1445, 1272, 1026. dH
(300 MHz, CDCl3) 7.49–7.38 (m, 5H), 4.05–3.97 (m, 4H), 2.60
(t, J 6.6, 2H), 2.43 (td, J 6.6, 2.7, 2H), 1.93 (quint., J 6.6, 2H),
1.76 (quint., J 6.6, 2H), 1.17 (td, J 6.6, 0.6, 6H). dC (75 MHz,
CDCl3) 202.5, 145.1 (d, J 7.1), 133.8, 129.5, 129.4, 128.3, 126.6
(d, J 7.4), 64.3 (d, J 6.0), 43.4, 30.9, 25.8, 25.5, 15.9 (d, J 7.4). m/
z (HR-ESI) Found (MþH)þ 339.1359, C17H23O5P requires
(MþH)þ 339.1361.
Diethyl (2-(furan-2-carbonyl)cyclohex-1-en-yl) phosphate
(7f). Prepared using the procedure described for compound
7a. Clear colourless oil. Rf 0.3 (1:1, v/v EtOAc/hexane).
n
max/cmꢁ1 2940, 1760, 1644, 1463, 1263, 1032. dH (300 MHz,
CDCl3) 7.54–7.51 (m, 1H), 7.14–7.10 (m, 1H), 6.54–6.42
(m, 1H), 3.84–3.74 (m, 4H), 2.40–2.38 (m, 2H), 2.30–2.19 (m,
2H), 1.76–1.62 (m, 2H), 1.60–1.53 (m, 2H), 1.31–1.05 (m, 6H).
dC (75 MHz, CDCl3) 183.7, 152.0, 147.6 (d, J 7.13), 146.8,
121.6 (d, J 8.55), 119.7, 112.0, 64.0 (d, J 6.52), 27.5, 25.8, 22.2,
21.3, 15.6 (d, J 6.83). m/z (HR-ESI) Found (MþH)þ, 329.1154,
C15H21O6P, requires (MþH)þ, 329.1149.
2-(2-Bromobenzoyl)cyclohex-1-en-yl diethyl phosphate (7c).
Clear colourless oil. Prepared using the procedure described for
compound 7a. Rf 0.2 (3:2, v/v EtOAc/hexanes). nmax/cmꢁ1
3563, 2938, 1652, 1367, 1294, 1137, 1033. dH (300 MHz,
CDCl3) 7.57 (dd, J 7.8, 1.2, 1H), 7.44 (dd, J 7.8, 2.1, 1H),
7.35 (td, J 7.8, 1.2, 1H), 7.24 (td, J 7.8, 2.1, 1H), 3.92–3.78
(m, 4H), 2.57–2.52 (m, 2H), 2.49–2.44 (m, 2H), 1.82–1.75
(m, 2H), 1.72–1.66 (m, 2H), 1.20 (td, J 7.2, 1.2, 6H). dC
(75 MHz, CDCl3) 195.5, 153.6 (d, J 6.6), 142.4, 133.0, 130.8,
2-Benzoylcyclohexa-1,5-dien-1-yl diethyl phosphate (7 g).
Prepared using the procedure described for compound 7a. Clear
colourless oil. Rf 0.2 (4:1, v/v EtOAc/hexanes). nmax/cmꢁ1

RESEARCH FRONT
1154
S. J. Ryan et al.
3494, 2985, 1643, 1579, 1367, 1288, 1030. dH (300 MHz,
CDCl3) 7.86 (dt, J 6.0, 1.2, 2H), 7.56–7.51 (m, 3H), 6.33–6.23
(m, 2H), 3.62–3.51 (m, 4H), 2.52–2.44 (m, 2H), 2.24–2.17 (m,
2H), 1.12 (td, J 7.1, 1.2, 6H). dC (75 MHz, CDCl3) 196.0, 146.3
(d, J 7.7), 138.5, 135.5, 132.4, 129.1, 128.2, 122.9 (d, J 1.7),
118.4 (d, J 8.6), 64.3 (d, J 6.6), 24.6, 22.6, 15.8 (d, J 6.9). m/z
(HR-ESI) Found (MþNa)þ 359.1017, C17H21O5P requires
(MþNa)þ 359.1024.
0.82 (d, J 6.9, 3H). dC (75 MHz, CDCl3) 136.9, 121.6, 80.1, 37.2,
31.7, 25.5, 25.0, 22.3, 19.5, 18.7. m/z (HR-EI) Found (Mꢂ)þ,
232.0458, C10H17BrO requires (Mꢂ)þ, 232.0463.
(2-Bromocyclohex-1-en-1-yl)(4-methoxyphenyl)methanol
(Table 2, entry 8) was prepared using the procedure described
above. Clear colourless oil. Rf 0.3 (1:4, v/v EtOAc/hexanes).
n
max/cmꢁ1 3427, 2934, 1725, 1611, 1509, 1247, 1036. dH
(300 MHz, CDCl3) 7.35 (d, J 8.7, 2H), 6.88 (d, J 8.7, 2H),
5.97 (s, 1H), 3.80 (s, 3H), 2.57–2.55 (m, 2H), 2.32–2.23 (m, 1H),
1.87–1.53 (m, 5H)/ dC (75 MHz, CDCl3) 158.9, 137.7, 133.8,
126.8, 121.2, 113.7, 75.1, 55.4, 37.1, 25.3, 24.9, 22.2. m/z (HR-
ESI) Found (Mꢂ)þ, 296.0241, C14H17BrO2 requires (Mꢂ)þ,
296.0412.
3-Benzoyl-1H-inden-2-yl diethyl phosphate (7h). Prepared
using the procedure described for compound 7a. Clear colour-
less oil. Rf 0.3 (1:1, v/v EtOAc/hexane). nmax/cmꢁ1 2985, 1731,
1602, 1450, 1222, 1035. dH (300 MHz, CDCl3) 7.94–7.91
(m, 2H), 7.60–7.22 (m, 7H), 3.93–3.87 (m, 4H), 2.04 (s, 2H),
1.23–1.17 (m, 6H). dC (75 MHz, CDCl3) 196.9, 178.4 (d, J 8.52),
143.2, 138.3, 137.7, 134.7, 129.3, 128.5, 127.9, 126.8, 125.6,
125.4, 107.8 (d, J 7.75), 63.3 (d, J 6.63), 42.2, 15.8 (d, J 6.83).
m/z (HR-EI) Found (M_)þ, 372.1131, C20H21O5P, requires (M_)þ,
372.1127.
(2-Bromocyclohept-1-en-1-yl)(phenyl)methanol (Table 2,
entry 9) was prepared using the procedure described above.
Clear colourless oil. Rf 0.3 (3:7, v/v EtOAc/hexane). nmax/cmꢁ1
3390, 2934, 1448, 1332, 1017. dH (300 MHz, CDCl3) 7.47–7.27
(m, 5H), 6.04 (s, 1H), 2.83 (d, J 6.3, 2H), 2.26–2.06 (m, 2H),
1.79–1.55 (m, 4H), 1.37–1.18 (m, 2H). dC (75 MHz, CDCl3)
142.8, 141.3, 128.1, 127.1, 125.2, 124.4, 76.4, 41.6, 31.5,
27.8, 26.4, 25.2. m/z (HR-ESI) Found (MþH)þ, 281.0535,
C14H17BrO, requires (MþH)þ, 281.0536.
Procedure for the haloformylation reaction
PBr3 (10.8 mL, 115 mmol) was added dropwise to a stirred
solution of DMF (9.8 mL, 128 mmol) in chloroform (75 mL) at
08C. The reaction mixture was allowed to stir for 1 h, at which
time the appropriate ketone (50 mmol) was added and the
mixture heated to reflux for an additional 3 h. The solution was
then cooled to room temperature, transferred to a flask of ice
water and neutralized with solid NaHCO3. The aqueous phase
was extracted with CH2Cl2 (3 ꢀ 50 mL) and the combined
organic layers washed with NaHCO3 (2 ꢀ 20 mL of a saturated
aqueous solution), dried (MgSO4) and the volatiles evaporated.
The resulting residue was purified by flash column chroma-
tography to afford, after concentration of the appropriate frac-
tions, compounds 10a,[14] 10o[15] and 10p,[16] which matched
previously reported data.
(2-Bromo-3,4-dihydronaphthalen-1-yl)(phenyl)methanol
(Table 2, entry 10) was prepared using the procedure described
above. Clear colourless oil. Rf 0.2 (3:7, v/v EtOAc/hexane).
n
max/cmꢁ1 3387, 3027, 2831, 1491, 1448, 1239, 1026. dC
(300 MHz, CDCl3) 7.56–7.52 (m, 2H), 7.42–7.36 (m, 2H),
7.33–7.25 (m, 2H), 7.16–7.12 (m, 2H), 7.04–6.98 (m, 1H),
6.46 (d, J 5.7, 1H), 3.12–2.86 (m, 4H), 2.70 (d, J 5.7, 1H,
-OH). dC (75 MHz, CDCl3) 141.24, 136.08, 135.56, 131.64,
128.37, 127.51, 127.06, 126.92, 126.33, 126.18, 125.63, 125.20,
74.38, 35.93, 29.52. m/z (HR-EI) Found (MþH)þ, 314.0308,
C17H15BrO, requires (MþH)þ, 314.0306.
1-(2-Bromo-3,4-dihydronaphthalen-1-yl)-2-methylpropan-
1-ol (Table 2, entry 11) was prepared using the procedure
described above. Clear colourless oil. Rf 0.3 (3:7, v/v EtOAc/
hexane). nmax/cmꢁ1 3448, 3061, 2957, 1480, 1016. dH
(300 MHz, CDCl3) 7.98–7.95 (m, 1H), 7.19–7.12 (m, 3H),
4.84 (d, J 10.2, 1H), 2.94–2.72 (m, 4H), 2.37–2.24 (m, 1H),
2.13 (s, 1H, -OH), 1.17 (d, J 6.6, 3H), 0.74 (d, J 6.6, 3H). dC
(75 MHz, CDCl3) 136.0, 133.0, 127.7, 127.4, 126.5, 126.2,
125.8, 119.9, 81.2, 36.5, 32.3, 30.1, 20.2, 19.2. m/z (HR-EI)
Found (Mꢂ)þ, 281.0533, C14H17BrO, requires (Mꢂ)þ, 281.0536.
Procedure for the Grignard addition reaction
The appropriate bromoaldehyde 10a, o or p (15 mmol) was
added dropwise to a stirred solution of R1MgX (23 mmol) in
THF (40 mL) at ꢁ788C. The reaction mixture was maintained at
this temperature, with stirring, for 1 h. At this time it was
quenched with NH4Cl (10 mL of a saturated aqueous solution).
The aqueous solution was extracted with EtOAc (3 ꢀ 20 mL)
and the combined organic layers washed with brine (20 mL),
dried (MgSO4) and the volatiles evaporated. The resulting res-
idue was purified by flash column chromatography to afford,
after concentration of the appropriate fractions, the title bromo
alcohols.
Procedure for the PCC oxidation to provide b-bromo
ketones 9
Bromoalcohols as prepared above (10 mmol) were dissolved in
CH2Cl2 (30 mL), pyridiniumchloro chromate (2.59 g, 12 mmol)
was then added and the mixture allowed to stir for 6–18 h at
room temperature. The solution was then diluted with ether
(10 mL) and passed through a plug of neutral alumina. The fil-
trate was concentrated under reduced pressure and the crude
residue purified by flash column chromatography to afford, after
concentration of the appropriate fractions, the bromo ketones 9.
Yields in Table 2 correspond to the formation of these com-
pounds in two-steps from the starting b-bromo aldehyde.
(2-Bromocyclohex-1-en-1-yl)(phenyl)methanone (9a) was
prepared as a pale yellow oil using the procedure described
above and provided 1H- and 13C-NMR spectra consistent with
the reported structure.[17]
(2-Bromocyclohex-1-en-yl(phenyl)methanol (Table 2, entries
1–5) was prepared as a clear colourless oil using the procedure
described above and provided 1H- and 13C-NMR spectra consis-
tent with the reported structure.[17]
1-(2-Bromocyclohex-1-en-1-yl)ethanol (Table 2, entry 6)
was prepared as a clear colourless oil using the procedure
1
described above and provided H- and 13C-NMR spectra con-
sistent with the reported structure.[15]
1-(2-Bromocyclohex-1-en-1-yl)-2-methylpropan-1-ol (Table 2,
entry 7) was prepared using the procedure described above. White
low melting solid. Rf 0.3 (1:9, v/v EtOAc/hexanes). nmax/cmꢁ1
3308, 2933, 1728, 1447, 1334, 1257, 1025. dH (300 MHz,
CDCl3) 4.37 (d, J 9.3, 1H), 2.54–2.49 (m, 2H), 2.34–2.26 (m,
1H), 2.05–1.96 (m, 1H), 1.83–1.59 (m, 5H), 1.04 (d, J 6.9, 3H),
1-(2-Bromocyclohex-1-en-1-yl)ethenone (9l) was prepared
as a pale yellow oil using the procedure described above and

RESEARCH FRONT
Enabling Discoveries in NHC Catalysis: Assembly of 1-acyl-2-alkylcycloalkenes
1155
provided 1H- and 13C-NMR spectra consistent with the reported
structure.[18]
NMP (9.0 equiv.) and b-bromoketone 7 (1.0 equiv.) in THF at
158C. The mixture was stirred at room temperature for 1 h then
quenched with HCl (1 M aqueous solution) and the phases
separated. The aqueous layer was extracted with diethyl ether
and washed with NaHCO3 (saturated aqueous solution). The
combined organic layers were dried (MgSO4), and the volatiles
evaporated. The resulting residue was purified by flash column
chromatography. Yields of isolated material are reported in
Table 2.
1-(2-Bromocyclohex-1-en-1-yl)-2-methylpropan-1-one (9m) was
prepared using the procedure described above. Pale yellow oil.
Rf 0.3 (1:9, v/v EtOAc/hexanes). nmax/cmꢁ1 2935, 1695, 1466,
1203, 980. dH (300 MHz, CDCl3) 3.13 (quint., J 7.2, 1H),
2.55–2.50 (m, 2H), 2.30–2.25 (m, 2H), 1.79–1.68 (m, 4H),
1.14 (d, J 7.2, 6H). dC (75 MHz, CDCl3) 211.0, 139.6, 119.7,
39.6, 36.1, 29.9, 24.3, 21.5, 18.1.
(2-Bromocyclohex-1-en-1-yl)(4-methoxyphenyl)methanone
(9n) was prepared using the procedure described above. Pale
yellow oil. Rf 0.3 (1:9, v/v EtOAc/hexanes). nmax/cmꢁ1 2935,
1660, 1598, 1508, 1253, 1170. dH (300 MHz, CDCl3) 7.91 (d, J
9.0, 2H), 6.96 (d, J 9.0, 2H), 3.88 (s, 3H), 2.62–2.58 (m, 2H),
2.35–2.31 (m, 2H), 1.86–1.77 (m, 4H). dC (75 MHz, CDCl3)
196.4, 164.2, 138.1, 132.1, 127.6, 119.7, 114.2, 55.6, 35.6, 29.8,
24.4, 21.6. m/z (HR-ESI) Found (MþH)þ, 295.0326,
C14H15BrO2 requires (MþH)þ, 295.0334.
(2-Methylenecyclohex-1-en-1-yl)(phenyl)methanone (6a)
was prepared as a clear colourless oil using both methods A
and B and provided 1H- and 13C-NMR spectra consistent with
the reported structure.[2c]
(2-Butylcyclohex-1-en-1-yl)(phenyl)methanone (6b) was
prepared using method A. Clear colourless oil. Rf 0.3 (1:9, v/v
EtOAc/hexanes). nmax/cmꢁ1 2928, 1660, 1447, 1277, 1246. dH
(300 MHz, CDCl3) 7.91–7.88 (m, 2H), 7.59–7.53 (m, 1H), 7.48–
7.43 (m, 2H), 2.22–2.19 (m, 2H), 2.14–2.11 (m, 2H), 1.87 (t, J
7.8, 2H), 1.74–1.69 (m, 4H), 1.36–1.26 (m, 2H), 1.56–1.08 (m,
2H), 0.74 (t, J 7.2, 3H). dC (75 MHz, CDCl3) 201.5, 138.3, 136.8,
132.9, 132.3, 129.2, 128.4, 34.7, 30.1, 28.3, 27.5, 22.5, 22.4,
22.2, 13.7. m/z (HR-EI) Found (M)þ, 242.1666, C17H22O
requires (M)þ, 242.1671.
(2-Bromophenyl)(2-methylcyclohex-1-en-1-yl)methanone
(6c) was prepared using method A. Clear colourless oil. Rf 0.3
(1:9, v/v EtOAc/hexanes). nmax/cmꢁ1 2932, 1667, 1644, 1430,
1289, 1236. dH (300 MHz, CDCl3) 7.57–7.54 (m, 1H), 7.36–
7.33 (m, 2H), 7.27–7.21 (m, 1H), 2.23–2.18 (m, 2H), 2.14–2.13
(m, 2H), 1.71–1.70 (m, 3H), 1.66–1.61 (m, 4H). dC (75 MHz,
CDCl3) 198.9, 145.5, 142.4, 133.3, 132.1, 131.0, 129.2, 127.4,
119.4, 33.5, 26.9, 22.3, 22.1, 21.7. m/z (HR-ESI) Found
(MþNa)þ, 301.0190, C14H15BrO requires (MþNa)þ, 301.0204.
(3-Bromophenyl)(2-methylcyclohex-1-en-1-yl)methanone
(6d) was prepared as a clear colourless oil using method A and
provided 1H- and 13C-NMR spectra consistent with the reported
structure.[2c]
(2-Bromocyclohept-1-en-1-yl)(phenyl)methanone (9o) was
prepared using the procedure described above. Pale yellow oil.
Rf 0.3 (1:19, v/v EtOAc/hexane). nmax/cmꢁ1 2925, 1667, 1595,
1448, 1260. dH (300 MHz, CDCl3) 7.94–7.91 (m, 2H), 7.56–
7.51 (m, 1H), 7.46–7.41 (m, 2H), 2.87–2.84 (m, 2H), 2.35–2.32
(m, 2H), 1.78–1.69 (m, 6H). dC (75 MHz, CDCl3) 197.2, 141.8,
134.0, 133.3, 129.3, 128.5, 123.5, 41.4, 31.6, 30.4, 25.8, 25.4.
m/z (HR-ESI) Found (MþH)þ, 279.0379, C14H15BrO, requires
(MþH)þ, 279.0379.
(2-Bromo-3,4-dihydronaphthanen-1-yl)(phenyl)methanone
(9p) was prepared, then directly subjected to cross-coupling, at
which point full characterization was performed on 6p.
1-(2-Bromo-3,4-dihydronaphthalen-1-yl)-2-methylpropan-
1-one (9q) was prepared using the procedure described above.
Pale yellow oil. Rf 0.2 (1:19, v/v EtOAc/hexane). nmax/cmꢁ1
3061, 1670, 1593, 1484, 1280. dH (300 MHz, CDCl3) 7.20–7.12
(m, 3H), 6.89–6.86 (m, 1H), 3.09 (quint., J 6.9, 1H), 2.99–2.93
(m, 2H), 2.86–2.80 (m, 2H), 1.20 (d, J 6.9, 6H). dC (75 MHz,
CDCl3) 209.5, 140.0, 133.2, 131.5, 128.0, 127.9, 126.9, 123.8,
120.6, 41.0, 34.3, 29.2, 17.9. m/z (HR-ESI) Found (MþH)þ,
279.0379, C14H15BrO, requires (MþH)þ, 279.0379.
Furan-2-yl(2-methylcyclohex-1-en-1-yl)methanone (6f) was
prepared using method A. Clear colourless oil. Rf 0.3 (1:19, v/v
EtOAc/hexane). nmax/cmꢁ1 2933, 1759, 1643, 1463, 1294,
1018. dH (300 MHz, CDCl3) 7.57–7.55 (m, 1H), 7.05–7.03
(m, 1H), 6.48–6.45 (m, 1H), 2.27–2.16 (m, 2H), 2.06–1.97
(m, 2H), 1.64–1.58 (m, 4H), 1.56 (s, 3H). dC (75 MHz, CDCl3)
188.5, 152.5, 146.3, 135.9, 131.6, 119.3, 112.1, 31.1, 27.0, 22.3,
22.1, 20.9. m/z (HR-ESI) Found (MþH)þ, 191.1068, C12H14O2,
requires (MþH)þ, 191.1067.
General procedures for the preparation
of 1-acyl-2-alkylcycloalkenes 6
Method A: From b-keto enol phosphate 7
1-Acyl-2-alkylcycloalkenes 6 were prepared according to
the procedure of Weiler,[8] from the corresponding enol phos-
phate intermediate 7. Thus, MeLi (4.0 equiv. of a 1.6-M solution
in Et2O) was added to a stirred solution of CuI (2.0 equiv.) in dry
Et2O at 08C. The resulting clear solution was cooled to ꢁ788C
and phosphate 5 (1.0 equiv.), slowly added. The mixture was
maintained at this temperature for 1 h after which time it was
quenched with NH4Cl (saturated aqueous solution), extracted
with Et2O, washed with dilute NH3 in brine, then brine, the
organics were dried (MgSO4), filtered, concentrated, and the
crude residue purified via flash column chromatography. Yields
of isolated material are reported in Table 1.
(2-Methylcyclohexa-1,3-dien-1-yl)(phenyl)methanone (6g)
was prepared as a clear colourless oil using method A and
provided 1H- and 13C-NMR spectra consistent with the reported
structure.[2c]
(2-methyl-1H-inden-3-yl)(phenyl)methanone (6h) was prepared
1
as a clear colourless oil using method A and provided H- and
13C-NMR spectra consistent with the reported structure.[2c]
(2-Ethylcyclohex-1-en-1-yl)(phenyl)methanone (6i) was pre-
pared as a clear colourless oil using method B and provided 1H-
and 13C-NMR spectra consistent with the reported structure.[2c]
Phenyl(2-propylcyclohex-1-en-1-yl)methanone (6j) was pre-
pared as a clear colourless oil using method B. Rf 0.3 (1:9, v/v
EtOAc/hexanes). nmax/cmꢁ1 2929, 1663, 1448, 1245. dH
(300 MHz, CDCl3) 7.91–7.89 (m, 2H), 7.59–7.50 (m, 1H),
7.46–7.41 (m, 2H), 2.23–2.20 (m, 2H), 2.13–2.10 (m, 2H),
1.86 (t, J 7.5, 2H), 1.75–1.66 (m, 4H), 1.42–1.30 (m, 2H),
0.73 (t, J 7.5, 3H). dC (75 MHz, CDCl3) 201.4, 138.0, 136.9,
132.9, 129.2, 128.4, 127.0, 36.9, 28.2, 27.6, 22.5, 22.2, 21.1,
Method B: From b-bromo cycloalkenone 9
1-Acyl-2-alkylcycloalkenes 6 were prepared according to
Cahiez,[11f] through iron catalyzed coupling with the corre-
sponding b-bromo ketones 9. Thus, R2MgBr (1.5 equiv.) was
slowly added to a stirred solution of Fe(acac)3 (0.01 equiv.),

RESEARCH FRONT
1156
S. J. Ryan et al.
13.9. m/z (HR-EI) Found (Mꢂ)þ, 228.1530, C16H20O requires
(Mꢂ)þ, 228.1514.
(b) L. Candish, D. W. Lupton, Org. Lett. 2010, 12, 4836. doi:10.1021/
OL101983H
(c) S. J. Ryan, L. Candish, D. W. Lupton, J. Am. Chem. Soc. 2011, 133,
4694. doi:10.1021/JA111067J
[3] (a) For examples of acyl azolium catalysis see: K. Y-K. Chow,
J. W. Bode, J. Am. Chem. Soc. 2004, 126, 8126. doi:10.1021/
JA047407E
(2-(But-3-en-1-yl)cyclohex-1-en-1-yl)(phenyl)methanone
(6k) was prepared as a clear colourless oil using method B and
provided 1H- and 13C-NMR spectra consistent with the reported
structure.[2c]
1-(2-Methylcyclohex-1-en-1-yl)methanone (6l) was pre-
pared as a clear colourless oil using method B and provided
1H- and 13C-NMR spectra consistent with the reported
structure.[19]
2-Methyl-1-(2-methylcyclohex-1-en-1-yl)propan-1-one
(6m) was prepared as a clear colourless oil using method B and
provided 1H- and 13C-NMR spectra consistent with the reported
structure.[2c]
(4-Methoxyphenyl)(2-methylcyclohex-1-en-1-yl)methanone
(6n) was prepared as a clear colourless oil using method B and
provided 1H- and 13C-NMR spectra consistent with the reported
structure.[2c]
(b) N. T. Reynolds, J. Read de Alaniz, T. Rovis, J. Am. Chem. Soc.
2004, 126, 9518. doi:10.1021/JA046991O
(c) For selected studies involving acyl azoliums, see: C. Burstein,
F. Glorius, Angew. Chem. Int. Ed. 2004, 43, 6205. doi:10.1002/ANIE.
200461572
(d) S. S. Sohn, E. L. Rosen, J. W. Bode, J. Am. Chem. Soc. 2004, 126,
1437 0. doi:10.1021/JA044714B
(e) A. Chan, K. A. Scheidt, Org. Lett. 2005, 7, 905. doi:10.1021/
OL050100F
(f) K. Zeitler, Org. Lett. 2006, 8, 637. doi:10.1021/OL052826H
(g) B. E. Maki, A. Chan, E. M. Phillips, K. A. Scheidt, Org. Lett. 2007,
9, 371. doi:10.1021/OL062940F
(h) H. U. Vora, T. Rovis, J. Am. Chem. Soc. 2007, 129, 13796.
doi:10.1021/JA0764052
(i) B. E. Maki, E. V. Patterson, C. J. Cramer, K. A. Sheidt, Org. Lett.
2009, 11, 3942. doi:10.1021/OL901545M
(j) E. M. Phillips, M. Wadamoto, H. S. Roth, A. W. Ott, K. A. Scheidt,
Org. Lett. 2009, 11, 105. doi:10.1021/OL802448C
(k) H. U. Vora, T. Rovis, J. Am. Chem. Soc. 2010, 132, 2860.
doi:10.1021/JA910281S
(2-Methylcyclohept-1-en-1-yl)(phenyl)methanone (6o) was
prepared as a clear colourless oil using method B and provided
1H- and 13C-NMR spectra consistent with the reported
structure.[2c]
(2-Methyl-3,4-dihydronaphthalen-1-yl)(phenyl)methanone
(6p) was prepared as a clear colourless oil using method B. Rf 0.2
(1:19, v/v EtOAc/hexane). nmax/cmꢁ1 3063, 2957, 1667, 1596,
1448, 1018. dH (300 MHz, CDCl3) 8.06–8.02 (m, 2H), 7.58–
7.52 (m, 1H), 7.46–7.41 (m, 2H), 7.19 (d, J 7.5, 1H), 7.12 (dt, J
7.5, 1.2, 1H), 7.04 (dt, J 7.5, 1.2, 1H), 6.84 (d, J 7.5, 1H), 2.97 (t,
J 8.4, 2H), 2.42 (t, J 8.4, 2H), 1.85 (s, 3H). dC (75 MHz, CDCl3)
199.3, 136.9, 136.6, 133.7, 133.3, 133.1, 132.7, 129.3, 128.5,
127.4, 126.5, 126.3, 124.0, 29.5, 27.7, 20.8. m/z (HR-ESI) Found
(MþH)þ, 249.1270, C18H16O, requires (MþH)þ, 249.1274.
2-Methyl-1-(2-methyl-3,4-dihydronaphthalen-1-yl)propan-
1-one (6q) was prepared using method B. Clear colourless oil. Rf
0.3 (1:19, v/v EtOAc/hexane). nmax/cmꢁ1 3061, 2957, 1671,
1448, 1282, 1018. dH(300 MHz, CDCl3) 7.15–7.11 (m, 3H),
6.80–6.77 (m, 1H), 2.91 (quint., J 6.6, 1H), 2.80 (t, J 8.1, 2H),
2.28 (d, J 8.1, 2H), 1.88 (s, 3H), 1.15 (d, J 6.6, 6H). dC (75 MHz,
CDCl3) 212.9, 136.4, 135.3, 134.5, 132.4, 127.5, 126.7, 126.5,
123.6, 40.9, 29.9, 27.9, 20.8, 18.0. m/z (HR-ESI) Found
(MþH)þ, 215.1431, C15H18O, requires (MþH)þ, 215.1430.
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