Mechanistic Studies of the Deslongchamps Annulation

Article abstract of DOI:10.1021/acs.joc.7b02341

The Cs₂CO₃-mediated annulations ("Deslongchamps annulations") of three spirocyclic benzoquinone monoketals 5b-d with an ester or acyl substituent at C-2 to two tert-butyl esters of λδ-unsaturated β-ketocarboxyl acids ("Nazarov reagents" 2a,b) were monitored ¹H NMR spectroscopically. This revealed that a primary product, by all likelihood the Michael adduct, forms fast and prior to the appearance of the Deslongchamps adduct. These primary products form reversibly. This was proved by two crossover and four scavenging experiments. Therein, components already incorporat.

Full text of DOI:10.1021/acs.joc.7b02341

Subscriber access provided by UNIVERSITY OF ADELAIDE LIBRARIES
Article
Mechanistic Studies of the Deslongchamps Annulation
Michael Kreibich, Denis Petrovi#, and Reinhard Brückner
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.7b02341 • Publication Date (Web): 13 Nov 2017
Downloaded from http://pubs.acs.org on November 15, 2017
Just Accepted
“Just Accepted” manuscripts have been peer-reviewed and accepted for publication. They are posted
online prior to technical editing, formatting for publication and author proofing. The American Chemical
Society provides “Just Accepted” as a free service to the research community to expedite the
dissemination of scientific material as soon as possible after acceptance. “Just Accepted” manuscripts
appear in full in PDF format accompanied by an HTML abstract. “Just Accepted” manuscripts have been
fully peer reviewed, but should not be considered the official version of record. They are accessible to all
readers and citable by the Digital Object Identifier (DOI®). “Just Accepted” is an optional service offered
to authors. Therefore, the “Just Accepted” Web site may not include all articles that will be published
in the journal. After a manuscript is technically edited and formatted, it will be removed from the “Just
Accepted” Web site and published as an ASAP article. Note that technical editing may introduce minor
changes to the manuscript text and/or graphics which could affect content, and all legal disclaimers
and ethical guidelines that apply to the journal pertain. ACS cannot be held responsible for errors
or consequences arising from the use of information contained in these “Just Accepted” manuscripts.
The Journal of Organic Chemistry is published by the American Chemical Society.
1155 Sixteenth Street N.W., Washington, DC 20036
Published by American Chemical Society. Copyright © American Chemical Society.
However, no copyright claim is made to original U.S. Government works, or works
produced by employees of any Commonwealth realm Crown government in the course
of their duties.

Page 1 of 21
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
Mechanistic Studies of the Deslongchamps Annulation
Michael Kreibich,[a] Denis Petrović,[a,b] and Reinhard Brückner*[a]
[a] Institut für Organische Chemie, AlbertꢀLudwigsꢀUniversität, Albertstraße 21, 79104 Freiburg im Breisgau, Germany
[b] New address: Cilag AG, Hochstr. 201, CHꢀ8205 Schaffhausen, Switzerland
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
Supporting Information
ABSTRACT: The Cs2CO3ꢀmediated annulations (“Deslongchamps annulations”) of three spirocyclic benzoquinone monoketals
5bꢀd with an ester or acyl substituent at Cꢀ2 to two tertꢀbutyl esters of γ,δꢀunsaturated βꢀketocarboxyl acids (“Nazarov reagents”;
2a,b) were monitored 1HꢀNMR spectroscopically. This revealed that a primary product, by all likelihood the Michael adduct, forms
fast and prior to the appearance of the Deslongchamps adꢀ
duct. These primary products form reversibly. This was
proved by two crossꢀover and four scavenging experiments.
Therein, components already incorporated in one of the
mentioned primary products ended up in Deslongchamps
adducts different from the one, which would have resulted
if the respective primary product had reacted alone. Howevꢀ
er, these experiments leave open whether our primary prodꢀ
ucts are intermediates en route to Deslongchamps products
or whether they represent dead ends.
ꢀ INTRODUCTION
Scheme 2). However, most references left this issue open,
simply referring to the process as an “anionic cycloaddition”.26
As described in the pioneering study,3 the simple diastereoseꢀ
The term “Deslongchamps annulation” acknowledges the
eponymous investigator´s merits for a [2+4] annulation apꢀ
lectivity of the Cs2CO3ꢀmediated Deslongchamps annulation
of the Nazarov reagent 2 (R = Me) with methyl cyclohexꢀ2ꢀenꢀ
1ꢀoneꢀ2ꢀcarboxylate (1, EWG = CO2Me, Rx = H) is solventꢀ
dependent: It furnished cis,synꢀ4 (EWG = CO2Me, R = Me, Rx
proach to functionalized decalin frameworks.1 It entails differꢀ
ent reactants than the [2+4] Robinson annulation: In Deslongꢀ
champs´ approach the two carbon atoms contributor is an acꢀ
ceptorꢀsubstituted cyclohexenone 1 while the four carbon atꢀ
= H) with 95:5 to 99.5:0.5 preferences over cis,antiꢀ4 (EWG =
oms contributor is a γ,δꢀunsaturated active methylene comꢀ
pound (“Nazarov reagent2”; Scheme 1). In most instances, the
latter is a γ,δꢀunsaturated βꢀketoester 2. Archetypical Deslongꢀ
champs annulations provide cisꢀfused decalindiones at the iniꢀ
tial stage (→3; 1 carbonyl group fully enolized) and after
de(alkoxycarbonylation) (→4). Deslongchamps annulations
have been used since 25 years for accessing cisꢀdecalins.3ꢀ21
The latter comprise a variety of steroids4,5,8ꢀ13,15 including the
cardenolides oubagenin16,18 and ouabain18 and a related tricyꢀ
clic triterpenoid named cassaine.20 Over the years the substrate
scope of this reaction has grown steadily.6,7,13,14,17,19,21
CO2Me, R = Me, Rx = H) in what were called "less polar solꢀ
vents" (benzene, THF, AcOEt, CHCl3, and CH2Cl2).3 In DMF
and MeCN, which were referred to as “very polar solvents”,
the cis,synꢀ4:cis,antiꢀ4 ratios were only 54:46 and 75:25, reꢀ
spectively.3 Deslongchamps and Lavallée interpreted these reꢀ
sults as "strong evidence for the existence of a DielsꢀAlder
mechanism in less polar solvents"3 and that "it is likely that the
reaction takes place via a sequential double Michael addition
in the more polar solvent"3,27
.
Scheme 1. Deslongchamps annulations of CO2tBu-
containing Nazarov reagents 2 with acceptor-substituted
cyclohexenones 1 (examples: ref.1) or with acceptor-
substituted benzoquinone monoketals 5a-d (examples:
ref.21). Deslongchamps annulations with compound 5b
were studied in the present investigation again and De-
slongchamps annulations with compounds 5c,d for the first
time.
A while ago we disclosed modified Deslongchamps annulaꢀ
tions.21 They employ benzoquinone monoketals 5 as the two
carbon atoms contributor (Scheme 1, bottom) and deliver cisꢀ
fused octalindiones both initially (→ cis,synꢀ6; 1 carbonyl
group fully enolized) and after removing the CO2tBu group
(→ cis,synꢀ7). The newly accessible products cis,synꢀ6 and
cis,synꢀ7 are valuable22 because they possess an extra C=C
bond compared to cis,synꢀ3 and cis,synꢀ4. It allows to perform
followꢀup transformations.23
Two mechanisms of Deslongchamps annulations are discussed
− or at least held possible − in the literature: a DielsꢀAlder reꢀ
action or two sequential Michael additions24,25
(
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 2 of 21
orientation30 (as defined in Scheme 1) in a number of cases but
in an antiꢀorientation31 more frequently.
1
2
3
4
5
6
7
8
9
Scheme 2. The Deslongchamps annulations of Scheme 1 as
an overall transformation (middle; the de-tert-butoxy-
carbonylation step is not comprised) and with regard to
the originally discussed mechanisms: concerted bond for-
mations at C-α and at C-δ (“anionic Diels-Alder reaction”;
top) vs. sequential bond formations at C-α first and at C-δ
subsequently (“sequential Michael additions"; bottom).[a]
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
kexo
kendo
O
O
O
O
Rx
OMe
OMe
Rx
R
H
R
H
anionic
Diels-Alder
reaction
O
tBuO
tBuO
O
O
O
We disagree with the preceding analysis with respect to the
concertedness of the annulation in “less polar solvents”. If one
accepts the DimrothꢀReichardt parameter ET(30) as a measure
for solvent polarity,28 the order of increasing polarity of the
mentioned solvents is the following: benzene (ET = 34.3), THF
(ET = 37.4), AcOEt (ET = 38.1), CHCl3 (ET = 39.1), CH2Cl2
(ET = 40.7), DMF (ET = 43.2), and MeCN (ET = 45.6). Firstly,
this ordering does not parallel the variation of the syn:antiꢀ
ratios. The latter rather increase from 95:5 in the least polar
exo-8 or -9
endo-8 or -9
H
H
,
H
H
, H
CO2Me
R
CO2Me
R
R
O
O
O
Cs2CO3,
CH2Cl2
CO2Me
+
without
OH
CO2tBu
cis,syn-3 or -6
O
OH
CO2tBu
cis,anti-3 or -6
Rx
Rx
Rx
CO2tBu
solvent, namely benzene (⇒ ꢀEa,formation of antiꢀ vs. synꢀadduct
=
1 or 5
2
1.65 kcal/mol), to 99.5:0.5 in CHCl3, i. e., at medium polarity
(⇒ ꢀEa,formation of antiꢀ vs. synꢀadduct = 3.13 kcal/mol), to decrease
sharply in the most polar solvents DMF (54:46) and MeCN
(75:25) (⇒ ꢀEa,formation of antiꢀ vs. synꢀadduct = 0.09 and 0.65 kcal/mol,
respectively). Secondly, the assumption that an increase of poꢀ
larity would benefit the DielsꢀAlder mechanism to a lesser exꢀ
tent than the sequential Michael additions appears questionꢀ
able. After deprotonating the Nazarov reagent to an acceptorꢀ
substituted enolate, the latter proceeds to react to an acceptorꢀ
free enolate. The DielsꢀAlder mechanism realizes this in a sinꢀ
gle step while the sequential Michael addition mechanism reꢀ
quires two steps because of the intermediacy of another accepꢀ
torꢀsubstituted enolate (10/11;
H
,
H
H
,
H
H
sequential
Michael
additions
O
H
O
O
O
OMe
R
Rx
OMe
R
Rx
H
O
H
H
tBuO
O
O
O
OtBu
iso-10 or - 11[a]
(= diastereomers, not conformers)
10 or 11
ksyn
kanti
[a]
For orbital overlap and ringꢀstrain constraints, respectively, the newly formꢀ
ing ring must adopt a boat (grey shades) rather than chair conformation (not
shown). The transition structures for the second Michael additions, i.e. 10/11
and isoꢀ10/isoꢀ11, are depicted with the highest possible similarity to the Dielsꢀ
Alder transition states exoꢀ8/exoꢀ9 and endoꢀ8/endoꢀ9 respectively. This shall
not express any energetical preference for these geometries, though.− In this
Scheme, each compound except the Nazarov reagent has a pair of formula
numbers. The first number in each such pair refers to a cyclohexadienone, a cyꢀ
clohexadienoneꢀbased transition state, a cyclohexadienoneꢀbased intermediate
or a cyclohexadienoneꢀbased product. The second number in each formula
number pair refers to the analogous cyclohexenone(ꢀbased species).
Scheme 2). Thus, neither mechanism changes the overall
charge nor does it create an additional charge. As a conseꢀ
quence we see no compelling reason why there should be a
sizable solvent effect at all, let alone a differential solvent efꢀ
fect. Thirdly, it should be remembered that there is no aꢀprioriꢀ
reason why a DielsꢀAlder reaction would be more subject to
simple diastereocontrol than a Michael addition.29 On top, it
seems unclear why simple diastereocontrol in a DielsꢀAlder
mechanism of the Deslongchamps annulation would favor the
synꢀ vs. the antiꢀdiastereomer of the annulation products (cisꢀ
3,
According to Deslongchamps et al.3 the acceptorꢀsubstituted
cyclohexenone 1 (EWG = CO2Me, Rx = H; Scheme 1), a parꢀ
ticular Nazarov reagent 2 (R = Me, Scheme 1), and Cs2CO3
gave the annulation product cis,synꢀ3 (EWG = CO2Me, Rx =
H, R = Me) via a sequential Michael addition pathway in aceꢀ
tonitrile. This statement was based on the following observaꢀ
tions: After 30 min7 at −15°C, the reactants delivered essenꢀ
tially what was called a “single Michael adduct”3 (53% yield7).
Scheme 2): A survey of the stereochemistry of the [4+2]ꢀ
annulation products, which were obtained from uncharged
1,3ꢀdienes and alkyl cyclohexꢀ2ꢀenꢀ1ꢀoneꢀ2ꢀcarboxylates (1,
EWG = CO2R; Scheme 1) − often in the presence of a Lewis
acid − reveals that the CO2R group ended up in a synꢀ
2
ACS Paragon Plus Environment

Page 3 of 21
The Journal of Organic Chemistry
When the latter was reꢀdissolved in acetonitrile at room temꢀ for our investigations comprised (1) monitoring the progress
perature, reꢀtreated with Cs2CO3 for 3.5 h,7 and freed from the
CO2tBu group by TsOH in refluxing benzene the followꢀup
product cis,synꢀ4 of the annulation product cis,synꢀ3 (EWG =
CO2Me, Rx = H, R = Me) resulted as a 68:323 or 70:307
cis,syn:cis,anti mixture (55% yield7). When the original reacꢀ
tants were combined in acetonitrile at room temperature right
from the beginning and reacted without an interruption and
then freed from the CO2tBu group they gave the same followꢀ
up product cis,synꢀ4 as a 75:25 cis,syn:cis,anti mixture.3,7 The
nearꢀidentity of these selectivities led the cited study3 to sugꢀ
gest that the Michael addition occurred on the annulation route
– as an “overture reaction” of sorts. A subsequent cyclization
would render the Deslongchamps adduct.3 However, this inꢀ
terpretation fails to recognize an alternative analysis: the Miꢀ
chael adduct in question forms off the annulation route in what
would be a “deadꢀend equilibrium”.32 When reꢀexposed to
Cs2CO3 in acetonitrile this Michael adduct might revert to the
reactants, which, thereupon, give the annulation product by an
anionic DielsꢀAlder reaction. The possibility that such Michael
adducts form reversibly was neither considered in the suggestꢀ
ed scenario of being formed on the annulation route.3
of the respective Deslongchamps annulations by discontinuous
probing, (2) performing crossꢀover experiments, and (3) exeꢀ
cuting scavenging experiments. Calculations were undertaken,
too, but did not help.33
1
2
3
4
5
6
7
8
ꢀ RESULTS AND DISCUSSION
Synthesizing Deslongchamps Adducts From Benzoquinone
Monoketals
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
The substrate portfolio of Scheme 3 allowed for six Deslongꢀ
champs annulations engaging the acceptorꢀsubstituted benzoꢀ
quinone monoketals 5bꢀd and the Nazarov reagents 2a34 and
b.35 We realized them as already reported21 (5b + 2a; 5d + 2a)
or for the first time (5b + 2b; 5c + 2a; 5c + 2b; 5d + 2b). After
purification by flashꢀchromatography on silica gel,36 this proꢀ
vided the Deslongchamps adducts cis,synꢀ6aꢀf in 71ꢀ95%
yield22 exclusively as enols (δOH = 12.49−12.62 ppm in CDCl3
solution) rather than βꢀketoesters (Scheme 4).
Scheme 3. Conceivable roles of Michael adducts during the
Deslongchamps annulations investigated in the present
study.
6a
cis,syn-
6c
cis,syn-
6e
cis,syn-
Figure 1. Single crystal structures of cis,syn-6a37 (left),
cis,syn-6c38 (middle), and cis,syn-6e39 (right) specifying the
relative configurations of the three newly generated stere-
ogenic centers.[a]
[a]
The decalin scaffolds are oriented like in the drawing of Scheme 3. Four of
the decalin substituents are depicted with bold bonds. The remainder of this ilꢀ
lustration uses thin bonds – for not obscuring the focus on the new stereocenꢀ
ters.
The cis,synꢀconfiguration of H at Cꢀ8a, EWG at Cꢀ4a, and R at
Cꢀ5 was proved for compounds 6a, c, and e by single crystal
structure analyses (c.f. Figure 137,38,39) and assumed by analogy
for compounds 6b, d, and f.
The incertitude about the mechanism of the Deslongchamps
annulation hampers designing novel cycloalkenonecarboxylate
/ Nazarov reagent pairs in order to expand the product portfoꢀ
lio. Having touched the field twice,17,21 we looked at the role
of Michael adducts in Deslongchamps annulations anew.
Scheme 3 specifies these entities as cesium enolates Csꢀ13ꢀ18.
It places them in the context of the three mechanistic variants
in line with the analyses of the preceding paragraphs. Howevꢀ
er, the Michael adducts Csꢀ13ꢀ18 in Scheme 3 are different
than Deslongchamps’: because their two carbon atoms conꢀ
tributors are acceptorꢀsubstituted benzoquinone monoketals
5bꢀd rather than cyclohexenones 1. The mechanistic toolꢀkit
Scheme 4. The Deslongchamps annulations, whose mecha-
nism was studied in the present investigation (details: see
text). The conceivable constitutional and configurational
isomers of the protonated forms of the Michael adducts de-
rived from the shown reactants are depicted in footnote
44.[a]
3
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 4 of 21
CO2Me
Me
O
Me
Me
O
1
2
3
4
5
6
7
CO2Me
H
H
H
Cs2CO3
CH2Cl2
+
H
H
H
O
OH
CO2tBu
OH
CO2tBu
O
O
O
O
CO2tBu
60
:
40
cis,syn-6a
(8% rel-% keto tautomer)
5b
2a
(1.05 equiv.)
3.47 ppm (s) 4.87 ppm (s)
7.20 ppm
(d, 4J = 3.1 Hz)
5.98 ppm
6.54 ppm
(d, J = 10.2 Hz) (d, J = 10.3 Hz)
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
[a]
Our studies for ref.21 had provided compound cis,syn-
6a in 89% yield and compound cis,syn-6b in 99% yield.
Figure 2. Progress with time (t) of the Deslongchamps an-
nulation numbered “1” in Scheme 4; after 80 min the ad-
duct cis,syn-6a21 had formed in 93% yield [yield quantifi-
cations: 300 MHz H-NMR integrals of characteristic res-
onances (indicated under the formulas) relative to the low-
The Deslongchamps adducts cis,synꢀ6aꢀf were deꢀtertꢀ
butoxycarbonylated in two steps (Scheme 4): 1) ester cleavage
by trifluoroacetic acid (0°C, 2 h); 2) decarboxylation of the
crude βꢀketocarboxylic acid (benzene; either room temperaꢀ
ture / 8 days or reflux / 2 h. After purification by flashꢀ
chromatography on silica gel,36 this furnished the decalindiꢀ
ones cis,synꢀ7aꢀf in up to 90% yield.22 An Xꢀray structural
analysis proved the (stereo)structure of compound cis,synꢀ7a
(as published earlier21).
1
field singlet (δAr-H = 7.66 ppm) of 2,4,6-tribromotoluene,
1
which was present as a H-NMR standard]. Overview plot
of concentration/time pairs on white background and, in
grey boxes, analogous close-up plots for the early stages of
this reaction. In the close-up at right, the vertical grey line
shows that after 1.5 min ≥90% 5b and >90% 2a were con-
sumed and ≤10% cis,syn-6a had formed.41
Monitoring Deslongchamps Annulations
We probed the Deslongchamps annulations of Scheme 4 at
room temperature for the intermediacy of Michael adducts. To
this end we monitored their progress HꢀNMR spectroscopiꢀ
Technically, the Deslongchamps annulations of Scheme 4
were monitored as follows. The benzoquinone monoketal 5bꢀd
[1 equiv.; 0.25 mmol except for preparing cis,synꢀ6c
(0.50 mmol) and cis,synꢀ6f (2.5 mmol)], the Nazarov reagent
2a,b (1.05 equiv.), and 2,4,6ꢀtribromotoluene (for calibrating
1
cally. This was done discontinuously, namely by sampling and
examining 10ꢀ12 aliquots from the respective reaction mixꢀ
ture.40 Each such mixture was heterogeneous because Cs2CO3
or the cesium enolates Csꢀ2, to which they should give rise, is
incompletely soluble41 in the solvent (in CH2Cl2). As a conseꢀ
quence we could not help changing the Cs2CO3/solute ratio by
our sampling. Therefore we could not aspire for concentraꢀ
tion/time profiles at an exactitude level, which would allowing
to calculate rate constants. Because of this limitation we did
not steady the progress of our annulations by a thermostat.
1
the HꢀNMR integrals; 0.50 equiv.) were dissolved in CH2Cl2
(4−40 mL; c5bꢀd = 0.06 mol/L). Each annulation was started by
adding solid Cs2CO3 (1.00 equiv.) while stirring magnetically
from then onward. Aliquots of 0.4 mL were sampled from the
resulting suspension by a plastic syringe starting after 1 min.
We sampled again after 2, 3, 4, 6, 8, 10, 20, 40, and 80 min
(and also after 160 and 320 min when monitoring the forꢀ
mation of cis,synꢀ6f). Each sample was applied without delay
to a short chromatography column filled with silica gel. Eluꢀ
tion with AcOEt (3 mL) and evaporation of the eluent providꢀ
ed 10ꢀ12 Cs2CO3ꢀfree mixtures per annulation. Their contents
of unconsumed starting materials 5 and 2 and already formed
1
annulates cis,synꢀ6a-f were quantified HꢀNMR spectroscopiꢀ
cally (300 MHz, CDCl3) relative to a fixed amount of 2,4,6ꢀ
tribromotoluene added as a standard.42
4
ACS Paragon Plus Environment

Page 5 of 21
The Journal of Organic Chemistry
1
2
3
4
5
6
7
8
9
10
Scheme 5. Cross-over experiment I.[a] Dieses Schema
verweist 2 × auf Lit.-stelle44.
Figure 3. Conceivable structures of the Michael adducts
13-18 intervening in the formation of the Deslongchamps
adducts 6a-d.
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
The resulting concentration/time diagrams (Figure 2 and in
Section SI-4 of the Supporting Information) show that reacꢀ
tants 2 and 5 are already gone after a minute or a few minutes
(vs. cis,synꢀ6f: after 4 min). Concomitantly, less than 10% of
whatever Deslongchamps adduct had formed, often considerꢀ
ably less. The yields of the latter surpassed the 70% threshold
no earlier than 7ꢀ37 min later(vs. cis,synꢀ6f: 5 h later). It reꢀ
quired an hour or so until the reactions giving cis,synꢀ6aꢀe
were mostly over. Undisputably, our Deslongchamps subꢀ
strates did not react to give Deslongchamps products directꢀ
ly.43 We stopped monitoring when yields of 93% cis,synꢀ6a
(Figure 2), 98% cis,synꢀ6b (2nd concentration/time diagram in
Section SI-4 of the Supporting Information), 89% cis,synꢀ6c
(3rd concentration/time diagram loc. cit.), 97% cis,synꢀ6d (4th
concentration/time diagram loc. cit.), 83% cis,synꢀ6e (5th conꢀ
centration/time diagram loc. cit.), and 82% cis,synꢀ6f (6th conꢀ
centration/time diagram loc. cit.) were attained. I. e., each
primary product − or Michael adduct44 (formula: Figure 3; corꢀ
roborated by isolating the latter starting from reactants 5b and
2a43) − had continued to react giving a Deslongchamps adꢀ
duct eventually.
[a]
We started the Deslongchamps annulations 5b + 2a → 13 → cis,synꢀ6a
(numbered “1” in Scheme 4) and 5c + 2b → 16 → cis,synꢀ6d (numbered “4” in
Scheme 4) separately but concomitantly. After 2 min we combined the two
mixtures. After 2 h the nature and relative amounts of the resulting Deslongꢀ
1
champs adducts were assessed HꢀNMR spectroscopically (500 MHz, CDCl3).
In addition to the “regular products” cis,synꢀ6a (resulting from 13) and cis,synꢀ
6d (resulting from 16) we found the “crossꢀover products” cis,synꢀ6b (resulting
from 5b + 2b) and cis,synꢀ6c (resulting from 5c + 2a). The latter pairings
would have been impossible if the Michael adducts 13 and 16 had not reꢀ
formed their respective precursors 5b/2a and 5c/2b over the course of the reacꢀ
tion time; that is, these Michael adducts form reversibly.
Performing Deslongchamps Annulations as Cross-Over
Experiments
We wondered whether our (surmised) Michael adducts44 preꢀ
cede Deslongchamps products by forming irreversibly on the
respective reaction coordinate. Dubbed “variant 2” in Scheme
3 this mechanism would entail Michael adducts as genuine inꢀ
termediates. Alternatively, our (surmised) Michael adducts44
might form reversibly. This is conceivable off or on the pathꢀ
way giving Deslongchamps adducts. It would correspond to
what Scheme 3 designates as the variants “1” and “3” of the
plausible Deslongchamps annulation mechanisms, respectiveꢀ
ly. In the “variant 1” mechanism the Michael adduct arises off
the formation route of the Deslongchamps adduct. Representꢀ
ing a dead end, this Michael adduct must revert to the subꢀ
strates before the latter have a chance to form the Deslongꢀ
champs adduct by an anionic DielsꢀAlder reaction. We disꢀ
carded the variant 2 mechanism – including an irreversible
Michael adduct fomation – and gained support for the variants
1 or 3 – having a reversible Michael adduct fomation in comꢀ
mon – by the crossꢀover experiments shown in Scheme 5 and
Scheme 6.
According to Scheme 5 two Deslongchamps annulations were
started as parallel reactions. In the first flask the benzoquinone
monoketal 5b and the Nazarov reagent 2a were poised for the
Deslongchamps annulation numbered “1” in Scheme 4. Howꢀ
ever, we let the reaction undisturbed for only 2 minutes. At
this duration the monitoring experiment of Figure 2 predicted
a ~90% yield of the Michael adducts44 13 and a ~10% yield of
the ensuing Deslongchamps adduct cis,synꢀ6a. In the second
flask we let the benzoquinone monoketal 5c and the Nazarov
reagent 2b initiate the Deslongchamps annulation numbered
“4” in Scheme 4, and again for only 2 minutes. For this moꢀ
ment in time the monitoring experiment of the 4th concentraꢀ
tion/time diagram in Section SI-4 of the Supporting Inforꢀ
mation let us expect the Michael adducts44 16 to have been
5
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 6 of 21
cursors 5b/2b and 5c/2a under the reaction conditions; i. e., these Michael adꢀ
ducts form reversibly.
formed in about 90% yield and the ensuing Deslongchamps
1
2
3
4
5
6
7
8
adduct cis,synꢀ6d in less than 10% yield. We then pooled the
two surmised 90:10 mixtures in a single flask. After another
118 min the Deslongchamps adducts, which had resulted by
then were worked up by filtering the reaction mixture through
a pad of silica, eluting with AcOEt, and evaporating the solꢀ
We started another pair of Deslongchamps annulations sepaꢀ
rately and in parallel – from the same substrates as before
(Scheme 5) but swapping their pairings (Scheme 6). In flask 1
the benzoquinone monoketal 5b and the Nazarov reagent 2b
were combined for undergoing the Deslongchamps annulation
numbered “2” in Scheme 4. In flask 2 the benzoquinone
monoketal 5c and the Nazarov reagent 2a were combined for
undergoing the Deslongchamps annulation “3”. We left the
first mixture undisturbed for 1 min and the second for 2 min.
These time laps should have sufficed for ca. 90% Michael adꢀ
ducts44 14 and 15, respectively, to form plus ca. 10% of the
Deslongchamps adducts cis,synꢀ6b and c, respectively. This
expectation followed from the closeꢀups in the earlier monitorꢀ
ings (2nd and 3rd concentration/time diagram in Section SI-4 of
the Supporting Information, respectively). Combining the two
reaction mixtures then, allowing them to react for another 118
min, working them up, and analyzing them NMRꢀ
spectroscopically like in Scheme 5 revealed the presence of
the regular Deslongchamps products cis,synꢀ6b (46 relꢀ%) and
cis,synꢀ6c (31 relꢀ%) and of the crossꢀover products cis,synꢀ6a
(6 relꢀ%) and cis,synꢀ6d (17 relꢀ%). Thus the constituents 5b
and 2b of the Michael adduct 14 ended up not only in the
“regular” Deslongchamps adduct cis,synꢀ6b but also in the
“crossed” Deslongchamps adducts cis,synꢀ6a and cis,synꢀ6d,
respectively. Similarly, the constituents 5c and 2a of the Miꢀ
chael adduct 15 ended up not only in the “regular” Deslongꢀ
champs adduct cis,synꢀ6c but in the “crossed” Deslongchamps
adducts cis,synꢀ6d and cis,synꢀ6a, respectively, as well. This
outcome would be inexplicable unless the Michael adducts 14
and 15 had formed reversibly, i. e., reꢀformed their precursors
5b/2b and 5c/2a, respectively, under the reaction conditions.
1
vent. A 500 MHz HꢀNMR spectrum of a CDCl3 solution of
the residue revealed the presence of not just two entities
[cis,synꢀ6a (28 relꢀ%) + cis,synꢀ6d (53 relꢀ%)] but four [+
cis,synꢀ6b (12 relꢀ%) + cis,synꢀ6c (7 relꢀ%)]. This observation
establishes that the Michael adducts 13 and 16 must have unꢀ
dergone >19% reversal to their precursors 5b/2a and 5c/2b,
respectively. Otherwise 5b could not have combined with 2b
giving the crossꢀover product cis,synꢀ6b and, likewise, 5c
could not have combined with 2a giving the crossꢀover prodꢀ
uct cis,synꢀ6c. Differently expressed, the occurrence of these
crossꢀover products proves that the Michael adducts 13 and 16
form reversibly.
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
Scheme 6. Cross-over experiment II.[a] Dieses Schema
verweist 2 × auf Lit.-stelle44.
CO2Me
iBu
Cs2CO3
(1.00 eq.),
CH2Cl2
O
iBu
O
CO2Me
mixed at
room temp.
+
room temp.,
1 min;
O
O
O
O
O
O
CO2tBu
CO2tBu
conjugate base of Micha-
el adduct isomers 14a-h
(formulas: footnote 45)
5b
2b
(1.00 eq.)
COMe
Me
Cs2CO3
(1.00 eq.),
CH2Cl2
O
Me
O
COMe
+
room temp.,
2 min;
O
O
O
O
O
O
CO2tBu
CO2tBu
work up
conjugate base of Micha-
el adduct isomers 15a-h
(formulas: footnote 45)
after 120 min;
5c
2a
(1.0 eq.)
and 1H NMR
We ascertained that the crossꢀover products cis,synꢀ6b/6c of
the crossꢀover experiment of Scheme 5 arose under kinetic,
not thermodynamic control. This was done by exposing a mixꢀ
ture of the Deslongchamps adducts cis,synꢀ6b and c to the
conditions of the crossꢀover experiment (CH2Cl2 solution,
2 equiv. of solid Cs2CO3, room temp.) but 3 times longer. Afꢀ
ter 1, 2, 3, and 6 h, 1HꢀNMR spectroscopic (500 MHz, CDCl3)
examinations revealed identity with the original mixture of
cis,synꢀ6b and c. If these Michael adducts had reverted to their
precursors with similar rates, the latter would have recomꢀ
bined to a total of 4 Michael adducts cis,synꢀ6aꢀd. Accordingꢀ
ly, the Deslongchamps annulations of Scheme 5 proceeded irꢀ
reversibly. An analogous exposure of the crossꢀover products
cis,synꢀ6a/6d of the crossꢀover experiment of Scheme 6 to a
suspension of solid Cs2CO3 in CH2Cl2 revealed that those
compounds formed irreversibly, too.
CO2Me
Me
CO2Me
iBu
5.98 ppm
O
5.95 ppm
O
(d, J = 10.2 Hz)
(d, J = 10.2 Hz)
3
3
H
H
H
H
2
O
2
O
OH
OH
6.54 ppm
(d, J = 10.3 Hz)
6.53 ppm
(d, J = 10.2 Hz)
O
O
CO2tBu
CO2tBu
cis,syn-6b
cis,syn-6a
6
:
17
:
:
46
:
31
+
+
COMe
COMe
O Me
O
iBu
6.01 ppm
5.98 ppm
(d, J = 10.2 Hz)
(d, J = 10.2 Hz)
3
3
H
H
H
H
2
O
2
O
OH
OH
CO2tBu
6.54 ppm
6.57 ppm
(d, J = 10.2 Hz)
O
O
(d, J = 10.3 Hz)
CO2tBu
cis,syn-6d
cross-over products
cis,syn-6c
regular products
[a]
We started the Deslongchamps annulations 5b + 2b → 14 → cis,synꢀ6b
(numbered “2” in Scheme 4) and 5c + 2a → 15 → cis,synꢀ6c (numbered “3” in
Scheme 4) separately and a delay of 1 min. 1 and 2 min, respectively, after
launching these reactions, we combined the two mixtures. After 2 h the nature
and relative amounts of the resulting Deslongchamps adducts were assessed
1HꢀNMR spectroscopically (500 MHz, CDCl3). In addition to the “regular
products” cis,synꢀ6b (resulting from 14) and cis,synꢀ6c (resulting from 15) we
found the “crossꢀover products” cis,synꢀ6a (resulting from 5b + 2a) and
cis,synꢀ6d (resulting from 5c + 2b). The latter pairings would have been imposꢀ
sible unless the Michael adducts 14 and 15 had reꢀformed their respective preꢀ
Scavenging Experiments
Crossꢀover experiments are elaborated variants of scavenging
experiments. For instance, the crossꢀover experiment of
Scheme 5 engaged (1) the benzoquinone monoketal 5b in a
preꢀreaction with the Nazarov reagent 2a and (2) the benzoꢀ
6
ACS Paragon Plus Environment

Page 7 of 21
The Journal of Organic Chemistry
quinone monoketal 5c in a preꢀreaction with the Nazarov reaꢀ tants 5b and 2a could still afford the Deslongchamps adduct
1
2
3
4
5
6
7
8
gent 2b. Whenever the first preꢀreaction proceeded backwards,
regenerating some benzoquinone monoketal 5b and an identiꢀ
cal amount of the Nazarov reagent 2a, chances were a scavꢀ
enging reagent for either of the latter was present due to the
concomitant partial reversal of the second preꢀreaction: the latꢀ
ter would provide the benzoquinone monoketal 5c, a scavenꢀ
ger for the mentioned Nazarov reagent 2a, along with the
Nazarov reagent 2b, a scavenger for the mentioned benzoquiꢀ
none monoketal 5b. In the experiments described in the folꢀ
lowing, we did not regenerate a pair of scavengers from a perꢀ
tinent preꢀreaction. We rather added a single scavenger as a
pure compound.
cis,synꢀ6a. Alternatively, the same Michael adduct 13 regenerꢀ
ated the benzoquinone monoketal 5b (along with 2a) such that
it could combine with the scavenger giving the Michael adduct
14 fast and the respective Deslongchamps adduct cis,synꢀ6b
slowly. In the event, a 1HꢀNMR analysis of the crude products
present after 3 h characterized them as a 59:41 mixture of the
Deslongchamps adduct cis,synꢀ6a of the original reactants and
the Deslongchamps adduct cis,synꢀ6b incorporating the scavꢀ
enger.45 The experiment shown in the bottom part of Scheme 7
began with the benzoquinone monoketal 5b and at first nothꢀ
ing but the Nazarov reagent 2b and from 1 min (2nd concentraꢀ
tion/time diagram in Section SI-4 of the Supporting Inforꢀ
mation) onward one equivalent of the Nazarov reagent 2a,
added as a scavenger. After 3 h, we had obtained a 64:36 mixꢀ
ture of the Deslongchamps adduct cis,synꢀ6b of the original
reactant pairing and the Deslongchamps adduct cis,synꢀ6a of
the scavenger.
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
Scheme 7. Scavenging experiments I, using the benzoqui-
none monoketal 5b.[a]
Cs2CO3
(1.00 eq.),
CH2Cl2;
room temp.,
2 min;
CO2Me
Me
It is noteworthy that we obtained oppositely composed mixꢀ
tures of the Deslongchamps adducts cis,synꢀ6a and cis,synꢀ6b
in the scavenging experiments for Scheme 7. No matter which
was the original and which scavenging Nazarov reagent, there
was a slight preference for delivering the Deslongchamps adꢀ
duct of the original reagent pairing. The respective yield difꢀ
ferences are 59%−41% = 18% and 64%−36% = 28%, respecꢀ
tively. If kinetic rather than thermodynamic control of the
portfolio of Deslongchamps adduct formation prevailed here
as in our crossꢀover experiments (Scheme 5, Scheme 6) these
yield differences would be due to the 2 minutes and 1 minute
advances, which the original reactant combinations had under
the conditions of Scheme 7. Unfortunately, the respective
monitorings (5b + 2a → cis,synꢀ6a: see Figure 2 for t = 2 min;
5b + 2b → cis,synꢀ6b: see 2nd concentration/time diagram in
Section SI-4 of the Supporting Information for t = 1 min) are
not sufficiently precise to bear on the suspicion that, in addiꢀ
tion, part of these yield biases stem from the Michael adducts
13 and 14 rather being on than off the Deslongchampsꢀ
delivering reaction coordinate.
O
then 2b (1.00 eq.); 3 h
O
O
O
Me
CO2tBu
conjugate base of Micha-
13a-h
el adduct isomers
(formulas: footnote 45)
O
scavenging product
regular product
CO2tBu
:
59
41
2a
(1.00 eq.)
CO2Me
Me
CO2Me
O
O
iBu
O
H
H
3
H
H
3
CO2Me
+
:
2
2
OH
CO2tBu
OH
CO2tBu
O
O
O
O
O
O
5b
iBu
cis,syn-6a
cis,syn-6b
64
36
scavenging product
regular product
CO2Me
iBu
O
O
CO2tBu
O
then 2a (1.00 eq.); 3 h
2b
(1.00 eq.),
O
O
CO2tBu
conjugate base of Micha-
Cs2CO3
(1.00 eq.),
CH2Cl2;
14a-h
el adduct isomers
(formulas: footnote 45)
room temp.,
1 min;
Scheme 8. Scavenging experiments II, using the benzoqui-
none monoketal 5c.[a]
[a]
Top: interfering in the formation of the Deslongchamps adduct cis,synꢀ6a
from the Nazarov reagent 2a via the Michael adduct 13 by adding, 2 min after
launching the respective reaction, the Nazarov reagent 2b as a scavenger (+ 5b
→ cis,synꢀ6b). Bottom: interfering in the formation of the Deslongchamps adꢀ
duct cis,synꢀ6b from the Nazarov reagent 2b via the Michael adduct 14 and by
adding, 1 min after launching the respective reaction, the Nazarov reagent 2a as
a scavenger (+ 5b → cis,synꢀ6a). In both experiments, the nature and relative
amounts of the resulting Deslongchamps adducts were assessed after 3 h 1Hꢀ
NMR spectroscopically (500 MHz, CDCl3).
Scheme 7 shows two scavenging experiments starting from the
benzoquinone monoketal 5b. The experiment reproduced in
the top half affected first just the Nazarov reagent 2a. After 2
min, the Michael adduct 13 should have resulted in ca. 90%
yield (cf. the respective monitoring experiment: Figure 2). We
added the Nazarov reagent 2b as a scavenger. From then onꢀ
ward, the original Michael adduct 13 and/or the original reacꢀ
7
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 8 of 21
Cs2CO3
(1.00 eq.),
CH2Cl2;
room temp.,
2 min;
COMe
Me
In the course of Deslongchamps annulations of acceptorꢀ
O
1
2
3
4
5
6
substituted benzoquinone monoketals (and, by extrapolation,
possibly also of acceptorꢀsubstituted cyclohexenones in genꢀ
eral) Michael adducts form within minutes, in about 90%
yield, and reversibly. None of this was known before. In conꢀ
trast, the Deslongchamps adducts formed irreversibly (and, by
extrapolation, related Deslongchamps adducts might do so as
well). This was neither demonstrated before.
then 2b (1.00 eq.); 3 h
O
O
O
Me
CO2tBu
conjugate base of Micha-
15a-h
el adduct isomers
(formulas: footnote 45)
O
scavenging product
regular product
CO2tBu
7
8
9
:
47
53
2a
(1.00 eq.)
COMe
Me
COMe
iBu
Viewed differently, our reactants underwent Michael additions
for starters and not DielsꢀAlder reactions. By this preference
they seized the only opportunity to form a C−C bond without
turning an acceptorꢀsubstituted into an acceptorꢀfree enolate.
Proceding to a Deslongchamps adduct from there – either by
an intramolecular Michael addition of the initial Michael adꢀ
duct or after dissociation into the reactants via an anionic
DielsꢀAlder reaction – requires going from an acceptorꢀ
substituted to an acceptorꢀfree enolate. Overcoming the correꢀ
sponding energy barrier seems to cost time – so much, in fact,
that the original Michael adducts formed reversibly rather than
irreversibly.
O
O
O
H
H
3
H
H
3
COMe
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
+
:
2
2
OH
CO2tBu
OH
CO2tBu
O
O
O
O
O
O
5c
iBu
cis,syn-6c
cis,syn-6d
39
61
scavenging product
regular product
COMe
iBu
O
O
CO2tBu
O
then 2a (1.00 eq.); 3 h
2b
(1.00 eq.),
O
O
CO2tBu
conjugate base of Micha-
el adduct isomers
(formulas: footnote 45)
Cs2CO3
(1.00 eq.),
CH2Cl2;
room temp.,
2 min;
16a-h
That property, however, prevented us from determining
whether these Michael adducts arose off the route to the Deꢀ
slongchamps adducts (mechanism “1” of Scheme 3) or on it
(mechanism “3” of Scheme 3). Accordingly, it remains unꢀ
known whether the productꢀforming step of Deslongchamps
annulations like ours is the second Michael addition or an aniꢀ
onic DielsꢀAlder reaction.46
[a]
Top: interfering in the formation of Deslongchamps adduct cis,synꢀ6c from
the Nazarov reagent 2a via the Michael adduct 15 by adding, 2 min after
launching the respective reaction, the Nazarov reagent 2b as a scavenger (+ 5c
→ cis,synꢀ6d). Bottom: interfering in the formation of the Deslongchamps adꢀ
duct cis,synꢀ6d from the Nazarov reagent 2b via the Michael adduct 16 by addꢀ
ing, 2 min after launching the respective reaction, the Nazarov reagent 2a as a
scavenger (+ 5c → cis,synꢀ6c). In both experiments, the nature and relative
amounts of the resulting Deslongchamps adducts were assessed after 3 h 1Hꢀ
NMR spectroscopically (500 MHz, CDCl3).
ꢀ EXPERIMENTAL SECTION
General Working Technique: All reactions were carried out unꢀ
der an N2ꢀatmosphere. Reaction flasks were dried in vacuo with a
heat gun prior to use. Liquids were added with a syringe through a
septum. Solids were added in an N2ꢀcounterflow. THF was disꢀ
tilled over potassium, Et2O over sodium/potassium alloy, and
CH2Cl2 was distilled over CaH2 under an N2ꢀatmosphere prior to
use. Other solvents and reagents were purchased and used without
further purification. Flash chromatography:36 MachereyꢀNagel
silica gel 60® (230ꢀ400 mesh). All eluents were distilled prior to
use. Chromatography conditions are documented as in, for examꢀ
ple, "[a cm × b cm, cC6H12:EtOAc = c:d (v:v), e mL] ... F10ꢀ20",
which means: a column with a diameter of a cm was packed with
b cm of silica, it was eluted with cC6H12 and EtOAc in a c:d ratio
(v:v), fractions of the size of e mL were taken, and the product
was isolated from fractions 10ꢀ20. Nuclear magnetic resonance
Scheme 8 is an analogous documentation of two scavenging
experiments starting from the benzoquinone monoketal 5c.
They concern successive additions of the Nazarov reagents 2a
and 2b (at top) and vice versa (at bottom). Proceeding as deꢀ
scribed for the scavenging experiments of Scheme 7, we found
that in either case we obtained a mixture of two Deslongꢀ
champs adducts (Scheme 8).45 Surprisingly, in either case the
major adduct stemmed from the Nazarov reagent, which was
added as the scavenger. This observation shows that the Miꢀ
chael adducts 15 and 16, which must have formed first (acꢀ
cording to the monitorings of the 3rd and 4th concentration/time
diagram in Section SI-4 of the Supporting Information, reꢀ
spectively) underwent extensive reversal to their precursors
5c/2a and 5c/2b, respectively, on the timeꢀscale of Deslongꢀ
champs adduct formation. However, the twoꢀfold predomiꢀ
nance of the scavenging product must have another reason: a
preferred loss and/or decomposition of the originally added
Nazarov reagent. In that context we note that the relative
amount of Cs2CO3 automatically dropped to 0.5 equiv. when
we added the second, that is scavenging Nazarov reagent.
1
spectra: Bruker Avance 500 (500 MHz and 125 MHz for H and
13C respectively), Bruker Avance 400 spectrometer (400 MHz and
100 MHz for 1H and 13C respectively) and Avance 300 specꢀ
1
trometer (300 MHz for H respectively) referenced internally by
1
the Hꢀ and 13C NMR signals of the solvent [CDCl3: 7.26 ppm
(1H) and 77.16 ppm (13C); (CD3)2CO: 2.05 ppm (1H) and
29.84 ppm (13C); (CH3)4Si: 0.00 ppm (1H) and 0.00 ppm (13C)].
1H NMR data are reported as follows: chemical shift (δ in ppm),
multiplicity (s for singlet; d for doublet; t for triplet; sept for sepꢀ
tet, m for multiplet; mc for symmetrical multiplet; br for broad
signal), number of protons (concluded from the integrals), couꢀ
pling constant(s) (Hz), specific assignment or integral. 13C NMR
data are reported in terms of chemical shift and assignment. For
AB signals the highꢀfield part was named A and the lowꢀfield part
ꢀ CONCLUSION
8
ACS Paragon Plus Environment

Page 9 of 21
The Journal of Organic Chemistry
B. The atom numbering used for NMR assignments follows the
The title compound was prepared from (E)ꢀ5ꢀmethylhexꢀ2ꢀenoic
1
2
3
4
5
6
7
8
IUPAC nomenclature unless noted otherwise. High-resolution
mass spectra were obtained on a Finnigan MAT 8200 instrument
(EI: 70 eV; CI/NH3: 110 eV) using an orbitrap analyzer. Ele-
mental analyses were obtained on a CHNS analysator Elementar
Vario EL. Melting points were determined in a Büchi melting
point apparatus using open glass capillaries and are uncorrected.
IR spectra were obtained on an FTꢀIR Perkin Elmer Paragon
1000 spectrometer as a film of the substance on a polyethyleneꢀ
foil (SpectraꢀTech Inc.; selfꢀabsorption may compete in the reꢀ
gions 2920ꢀ2850, 1480ꢀ1430, and 740ꢀ700 cm–1.
acid and monoꢀtertꢀbutylmalonate. Oxalyl chloride (3.0 mL,
35 mmol, 1.1 equiv.) was added dropwise to a solution of DMF
(2.7 mL, 34 mmol, 1.1 equiv.) in CH2Cl2 (31 mL) at –10°C within
5 min. (E)ꢀ5ꢀMethylhexꢀ2ꢀenoic acid (4.0 g, 31 mmol, 1.0 equiv.)
was added in one portion. The mixture was stirred for 35 min. In
another flask iPrMgCl (2.8 M, 45 mL, 4.1 equiv.) was added at
0°C dropwise to a solution of monoꢀtertꢀbutylmalonate (10 mL,
66 mmol, 2.1 equiv.) in THF (47 mL). The mixture was stirred for
10 min. At 0°C the solution of the acid chloride was added dropꢀ
wise within 30 min via cannula to the solution of the magnesium
enolate. The resulting mixture was stirred for 30 min at room
temp. The reaction was quenched at 0°C by the addition of HCl
(conc., 20 mL) and water (20 mL). The layers were separated. The
aqueous layer was extracted with EtOAc (3 × 80 mL). The comꢀ
bined organic layers were washed with a saturated aqueous soluꢀ
tion of NH4CO3 (3 × 80 mL) until the aqueous layer was no longꢀ
er acidic. The combined aqueous layers were reꢀextracted with
EtOAc (2 × 80 mL). The combined organic layers were dried over
MgSO4. The solvent was evaporated and the residue was purified
by flash chromatography on silica gel36 [7.5 cm × 16.5 cm,
cC6H12:EtOAc 100:1 (v:v) to 2:1, 100 mL] to render the title
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
Synthesizing Nazarov Reagents and Benzoquinone Mono-
ketals:
tert-Butyl (E)-3-Oxohex-4-enoate (2a)
1
compound (F21ꢀ33; 3.89 g, 55%) as a pale yellow oil. H NMR
The title compound was prepared from crotonic acid and monoꢀ
tertꢀbutylmalonate:47 Oxalyl chloride (4.4 mL, 52 mmol,
1.1 equiv.) was added dropwise to a solution of DMF (4.0 mL,
51 mmol, 1.1 equiv.) in CH2Cl2 (45 mL) at –10°C within 5 min.
Crotonic acid (4.0 g, 47 mmol, 1.0 equiv.) was added in one porꢀ
tion. The mixture was stirred for 45 min. In another flask iPrMgCl
(300.13 MHz, CDCl3): δ = 0.91 (d, J8,7 = 6.2 Hz, 6H, 2 × CH3 of
enol), 0.93 (d, J8,7 = 6.2 Hz, 6H, 2 × CH3 of keto), 1.46 (s, 9H, tBuof
keto), 1.49 (s, 9H, tBuof enol), 1.73 (mc, 1H, 7ꢀHof enol), 1.78 (mc, 1H,
4
7ꢀHof keto), 2.06 (ddd, J6,5 = 7.6 Hz, J6,7 = 6.7 Hz, J6,4 = 1.3 Hz,
4
2H, 6ꢀH2 of enol), 2.13 (ddd, J6,5 = 7.3 Hz, J6,7 = 6.8 Hz, J6,4
=
1.4 Hz, 2H, 6ꢀH2 of keto), 3.48 (s, 2H, 2ꢀH2 of keto), 4.90 (s, 1H, 2ꢀHof
4
4
(1.9
M
, in THF, 0.1 L, 4.1 equiv.) was added dropwise to a soluꢀ
enol), 5.74 (dqd, J4,5 = 15.5 Hz, J4,6 = 1.4 Hz, J4, 3ꢀOH = 1.4 Hz,
tion of monoꢀtertꢀbutylmalonate (15 mL, 98 mmol, 2.1 equiv.) in
THF (70 mL) at 0°C. Stirring was continued for 10 min. At 0°C
the solution obtained from crotonic acid was added dropwise
within 30 min via cannula to the solution of the magnesium enoꢀ
late. The resulting mixture was stirred at room temp. for another
30 min. The reaction was quenched by adding HCl (conc., 15 mL)
and water (20 mL). The layers were separated. The aqueous layer
was extracted with EtOAc (3 × 80 mL). The combined organic
layers were washed with a saturated aqueous solution of NaHCO3
(3 × 80 mL) until the aqueous layer was no longer acidic. The
combined aqueous layers were reꢀextracted with EtOAc (2 ×
80 mL). The combined organic layers were dried over MgSO4.
The solvent was evaporated and the residue was purified by flash
chromatography on silica gel36 [7.5 cm × 15 cm, cC6H12:EtOAc
10:1 (v:v) to 2:1, 100 mL] to render the title compound (F9ꢀ12;
3.95 g, 46%) as a pale orange oil. 1H NMR (300.13 MHz,
CDCl3): δ = 1.46 (s, 9H, tBuof keto), 1.49 (s, 9H, tBuof enol), 1.85
(dd, 2H, J6,5 = 6.9 Hz, 4J6,4 = 1.6 Hz, 6ꢀH3 of enol), 1.93 (dd, 3H, J6,5
= 6.8 Hz, 4J6,4 = 1.7 Hz, 6ꢀH3 of keto), 3.47 (s, 2H, 2ꢀH2 of keto), 4.87
1H, 4ꢀHof enol), 6.14 (dt, J4,5 = 15.8 Hz, 4J4,6 = 1.4 Hz, 1H, 4ꢀHof keꢀ
to), 6.59 (dt, J5,4 = 15.3 Hz, J5,6 = 7.6 Hz, 1H, 5ꢀHof enol), 6.85 (dt,
4
J5,4 = 15.8 Hz, J5,6 = 7.4 Hz, 1H, 5ꢀHof keto), 12.03 (d, J3ꢀOH,4
=
1.1 Hz, 1H, 3ꢀOHof enol). The preceding NMR signals agree with
the literature.21
Methyl 8-Oxo-1,4-dioxaspiro[4.5]deca-6,9-diene-7-carboxylate
(5b)
A
solution
of
methyl
2ꢀhydroxyꢀ5ꢀ(2ꢀ
5.55 mmol,
hydroxyethoxy)benzoate47
(1.18 g,
1.0 equiv.) and NaHCO3 (1.59 g, 18.9 mmol,
3.4 equiv.) in CH2Cl2 (110 mL) was stirred at room
temp. for 20 min under exclusion of light. PhI(O2CCF3) (2.87 g,
6.66 mmol, 1.2 equiv.) was added in one portion and stirring was
continued for 30 min. The reaction mixture was cooled to 0°C,
washed with ice cold water (110 mL), and the layers were sepaꢀ
rated immediately. The organic layer was recooled in an ice bath
for 3 min and washed with iceꢀcold water once more (110 mL).
The layers were separated immediately. The organic layer was
dried over MgSO4. The solvent was evaporated at a maximum of
30°C (water bath) and the residue was immediately (previously
prepared) purified by flash chromatography on silica gel36
[3.5 cm × 10 cm, cC6H12:EtOAc:CH2Cl2 3:1:1 (v:v:v), 20 mL] to
render the title compound (F7ꢀ9; 330 mg, 93%) as a yellow solid.
4
(s, 1H, 2ꢀHof enol), 5.77 (dqd, 1H, J4,3 = 15.4 Hz, J4,6 = 1.7 Hz,
4
4J4,3ꢀOH = 1.6 Hz, 4ꢀHof enol), 6.18 (qd, 1H, J4,5 = 15.8 Hz, J4,6
=
1.7 Hz, 4ꢀHof keto), 6.62 (qd, 1H, J5,4 = 15.4 Hz, J5,6 = 6.9 Hz, 5ꢀHof
enol), 6.89 (qd, 1H, J5,4 = 15.8 Hz, J5,6 = 6.8 Hz, 5ꢀHof keto), 12.01
4
(d, 1H, J3ꢀOH,4 = 1.3 Hz, 3ꢀOHof enol). These NMR signals agree
with the literature.7
1
Melting point: 40ꢀ43°C. H NMR (400.13 MHz, CDCl3): δ =
3.84 (s, 3H, OMe), 4.17 (s, 4H, 2ꢀH2 and 3ꢀH2), 6.20 (d, J9,10
=
tert-Butyl (E)-7-Methyl-3-oxooct-4-enoate (2b)
4
10.2 Hz, 1H, 9ꢀH), 6.60 (dd, J10,9 = 10.2 Hz, J10,6 = 3.1 Hz, 1H,
4
10ꢀH), 7.20 (d, J6,10 = 3.1 Hz, 1H, 6ꢀH). 13C NMR (100.6 MHz,
CDCl₃): δ = 52. 7 (OMe)A, 66.2 (Cꢀ2 and Cꢀ3)A, 98.3 (Cꢀ5)B,
129.9 (Cꢀ9)A, 130.9 (Cꢀ7)B, 142.3 (Cꢀ10)A, 146.9 (Cꢀ6)A, 164.1
[(C=O)OMe]B, 181.1 (Cꢀ8)B; A the indicated 13C nuclei – they are
nonꢀquaternary – were identified in an edHSQC spectrum by their
B
crosspeaks with directly bonded protons; the indicated 13C nuꢀ
9
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 10 of 21
clei are quaternary and were distinguished in an HMBC spectrum
H). IR (CDCl3): ν̃ = 2895, 1700, 1675, 1640, 1385, 1360, 1285,
2
3
4
1250, 1145, 1030, 975, 945, 830, 745 cm−1. Elemental analysis:
C10H10O4 (194.2); Calcd: C: 61.85%, H: 5.19%; found: C:
61.96%, H: 5.32%. HRMS (pos. APCI) m/z: [M + H]+ calcd for
C10H11O4, 195.0652; found, 195.0653.
1
2
3
4
5
6
7
8
by their crosspeaks due to J, J and/or J couplings to "remote"
protons. edHSQC ["shortꢀrange C,HꢀCOSY spectrum"
(100.6/400.13 MHz), CDCl₃] [δC(13C) ↔ δH(1H)]: δC = 52.7
(OMe) ↔ δH = 3.84 (OMe); δC = 66.2 (Cꢀ2 and Cꢀ3) ↔ δH = 4.17
(2ꢀH2 and 3ꢀH2); δC = 129.9 (Cꢀ9) ↔ δH = 6.20 (9ꢀH); δC = 142.3
(Cꢀ10) ↔ δH = 6.60 (10ꢀH); δC = 146.9 (Cꢀ6) ↔ δH = 7.20 (6ꢀH).
HMBC ["longꢀrange C,HꢀCOSY spectrum" (100.6/400.13 MHz),
CDCl₃] [δC(13C) ↔ δH(1H)]: δC = 98.3 (Cꢀ5) ↔ δH = 4.17 (2ꢀH2
and 3ꢀH2), δH = 6.20 (9ꢀH), δH = 6.60 (10ꢀH), and δH = 7.20 (6ꢀ
H); δC = 130.9 (Cꢀ7) ↔ δH = 3.84 (OMe), δH = 6.20 (9ꢀH), δH =
6.60 (10ꢀH), and δH = 7.20 (6ꢀH); δC = 164.1 [(C=O)OMe] ↔ δH
= 3.84 (OMe), δH = 6.20 (9ꢀH), and δH = 7.20 (6ꢀH); δC = 181.1
(Cꢀ8) ↔ δH = 6.20 (9ꢀH), δH = 6.60 (10ꢀH), and δH = 7.20 (6ꢀH).
DQF-COSY ["H,HꢀCOSY spectrum" (400.13 MHz), CDCl3]
7-Benzoyl-1,4-dioxaspiro[4.5]deca-6,9-dien-8-one (5d)
[2ꢀHydroxyꢀ5ꢀ(2ꢀhydroxyethoxy)phenyl]phenylꢀ
methanone47 (501 mg, 1.49 mmol, 1.0 equiv.)
and NaHCO3 (490 mg, 5.83 mmol, 3.0 equiv.)
were suspended in CH2Cl2 (39 mL) and the susꢀ
pension was stirred at room temp. for 20 min
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
under exclusion of light. PhI(O2CCF3)2 (919 mg, 2.14 mmol,
1.1 equiv.) was added in one portion and stirring was continued
for 30 min. The reaction mixture was cooled in an ice bath for
5 min and washed with ice cold water (70 mL). The layers were
separated immediately and the organic layer was cooled in an ice
bath for 3 min and again washed with ice cold water (60 mL). The
layers were separated immediately and the organic layer was dried
over MgSO4. The solvent was evaporated at a maximum of 30°C
(water bath) and the residue was immediately (previously preꢀ
pared) purified by flash chromatograpy on silica gel36 [3 cm ×
10 cm, cC6H12:EtOAc:CH2Cl2 3:1:1 (v:v:v), 20 mL] to render the
title compound (F6ꢀ14; 437 mg, 88%) as a yellow solid. Melting
[δH(1H) ↔ δH(1H)]: δH = 6.60 (10ꢀH) ↔ δH = 6.20 (9ꢀH); δH
7.20 (6ꢀH) ↔ δH = 6.60 (10ꢀH). IR (CDCl3): ν = 3055, 2990,
=
̃
2955, 2900, 2850, 1745, 1685, 1650, 1275, 1220, 1140, 1045,
980, 945, 915 cm−1. HRMS (pos. APCI) m/z: [M + H]+ calcd for
C10H11O5, 211.0601; found, 211.0601.
7-Acetyl-1,4-dioxaspiro[4.5]deca-6,9-dien-8-one (5c)
1ꢀ(2ꢀHydroxyꢀ5ꢀ(2ꢀhydroxyethoxy)phenyl)ethanꢀ1ꢀ
one47 (201 mg, 1.02 mmol, 1.0 equiv.) and NaHCO3
(297 mg, 3.06 mmol, 3.0 equiv.) were suspended in
1
point: 83ꢀ85°C. H NMR (400.13 MHz, CDCl3): δ = 4.17 (mc,
4H, 2ꢀH2, 3ꢀH2), 6.25 (d, J9,10 = 10.1 Hz, 1H, 9ꢀH), 6.70 (dd, J10,9
4
CH2Cl2 (20 mL) and the suspension was stirred at
= 10.1 Hz, J10,6 = 3.1 Hz, 1H, 10ꢀH), 6.77 (d, J6,10 = 3.1 Hz, 1H,
room temp. for 20 min under exclusion of light. PhI(O2CCF3)2
(482 mg, 1.12 mmol, 1.1 equiv.) was added in one portion and
stirring was continued for 30 min. The reaction mixture was
cooled in an ice bath for 5 min and washed with ice cold water
(35 mL). The layers were separated immediately and the organic
layer was cooled in an ice bath for 3 min and washed again with
ice cold water (35 mL). The layers were separated immediately.
The organic layer was dried over MgSO4. The solvent was evapoꢀ
rated at a maximum of 30°C (water bath) and the residue was
immediately purified by flash chromatography on silica gel36
[2 cm × 10 cm, cC6H12:EtOAc:CH2Cl2 7:3:1 (v:v:v), 9 mL]. This
rendered the title compound (F3ꢀ9; 170 mg, 86%) as a pale orange
6ꢀH), 7.43ꢀ7.48 (m, 2H, metaꢀH2), 7.56ꢀ7.61 (m, 1H, paraꢀH),
7.82ꢀ7.84 (m, 2H, orthoꢀH2). 13C NMR (100.6 MHz, CDCl3): δ =
66.2 (Cꢀ2 and Cꢀ3)A, 98.3 (Cꢀ5)B, 128.7 (Cꢀmeta)A, 129.3 (Cꢀ9)A,
129.7 (Cꢀortho)A, 134.0 (Cꢀpara)A, 136.3 (Cꢀipso)B, 138.8 (Cꢀ7)B,
A
142.6 (Cꢀ6)A, 143.5 (Cꢀ10)A, 182.9 (Cꢀ8)B, 192.7 [(C=O)Ph]B;
the indicated 13C nuclei – they are nonꢀquaternary – were identiꢀ
fied in an edHSQC spectrum by their crosspeaks with directly
B
bonded protons; the indicated 13C nuclei are quaternary and
were distinguished in a HMBC spectrum by their crosspeaks due
to 2J, 3J and/or 4J couplings to "remote" protons. edHSQC
["shortꢀrange C,HꢀCOSY spectrum" (100.6/400.13 MHz), CDCl3]
[δC(13C) ↔ δH(1H)]: δC = 66.2 (Cꢀ2 and Cꢀ3) ↔ δH = 4.17 (2ꢀH2,
3ꢀH2); δC = 128.7 (Cꢀmeta) ↔ δH = 7.46 (metaꢀH); δC = 123.0 (Cꢀ
9) ↔ δH = 6.25 (9ꢀH); δC = 129.7 (Cꢀortho) ↔ δH = 7.83 (orthoꢀ
H); δC = 134.0 (Cꢀpara) ↔ δH = 7.61 (paraꢀH); δC = 142.6 (Cꢀ6)
↔ δH = 6.77 (6ꢀH); δC = 143.5 (Cꢀ10) ↔ δH = 6.70 10ꢀH).
HMBC ["longꢀrange C,HꢀCOSY spectrum" (100.6/400.13 MHz),
CDCl3] [δC(13C) ↔ δH(1H)]: δC = 98.3 (Cꢀ5) ↔ δH = 4.17 (2ꢀH2,
3ꢀH2), δH = 6.25 (9ꢀH), and δH = 6.77 (6ꢀH); δC = 136.3 (Cꢀipso)
↔ δH = 7.46 (metaꢀH); δC = 138.8 (Cꢀ7) ↔ δH = 6.25 (9ꢀH) and
δH = 6.77 (6ꢀH); δC = 182.9 (Cꢀ8) ↔ δH = 6.25 (9ꢀH), δH = 6.70
(10ꢀH), and δH = 6.77 (6ꢀH); δC = 192.7 [(C=O)Ph] ↔ δH = 6.25
(9ꢀH), δH = 6.77 (6ꢀH), and δH = 7.83 (orthoꢀH). DQF-COSY
["H,HꢀCOSY spectrum" (400.13 MHz), ] [δH(1H) ↔ δH(1H)]: δH
= 6.70 10ꢀH ↔ δH = 6.25 (9ꢀH); δH = 6.77 (6ꢀH) ↔ δH = 6.70 10ꢀ
H; δH = 7.58 (paraꢀH) ↔ δH = 7.46 (metaꢀH); δH = 7.83 (orthoꢀH)
1
oil. H NMR (500.32 MHz, CDCl3): δ = 2.51 (s, 3H, COMe ),
4.17 (s, 4H, 2ꢀH2, 3ꢀH2), 6.19 (d, J9,10 = 10.1 Hz, 1H, 9ꢀH), 6.62
4
(dd, J10,9 = 10.1 Hz, J10,6 = 3.2 Hz, 1H, 10ꢀH), 7.13 (d, J6,10
=
3.2 Hz, 1H, 6ꢀH). 13C NMR (500.3 MHz, CDCl3): δ = 30.9
(COMe)A, 66.2 (Cꢀ2, Cꢀ3)A, 98.5 (Cꢀ5)B, 130.0 (Cꢀ9)A, 137.0 (Cꢀ
7)B, 142.8 (Cꢀ10)A, 146.0 (Cꢀ6)A, 183.5 (Cꢀ8)B, 197.4 (COMe)B; A
the indicated 13C nuclei – they are nonꢀquaternary – were identiꢀ
fied in an edHSQC spectrum by their crosspeaks with directly
bonded protons; the indicated 13C nuclei are quaternary and
B
were distinguished in a HMBC spectrum by their crosspeaks due
to 2J, 3J and/or 4J couplings to "remote" protons. edHSQC
["shortꢀrange C,HꢀCOSY spectrum" (125.8/500.32 MHz), CDCl3]
[δC(13C) ↔ δH(1H)]: δC = 30.9 (COMe) ↔ δH = 2.51 (COMe); δC
= 66.3 (Cꢀ2, Cꢀ3) ↔ δH = 4.17 (2ꢀH2, 3ꢀH2); δC = 130.0 (Cꢀ9) ↔
δH = 6.19 (9ꢀH); δC = 142.8 (Cꢀ10) ↔ δH = 6.62 (10ꢀH); δC
=
↔ δH = 7.46 (metaꢀH). IR (CDCl3): ν̃ = 3060, 2960, 2895, 1680,
146.0 (Cꢀ6) ↔ δH = 7.13 (6ꢀH). HMBC ["longꢀrange C,HꢀCOSY
spectrum" (125.8/500.32 MHz), CDCl3] [δC(13C) ↔ δH(1H)]: δC =
98.5 (Cꢀ5) ↔ δH = 4.17 (2ꢀH2, 3ꢀH2), δH = 6.19 (9ꢀH), δH = 6.62
(10ꢀH), and δH = 7.13 (6ꢀH); δC = 137.0 (Cꢀ7) ↔ δH = 2.51
([CO]Me ), δH = 6.19 (9ꢀH), and δH = 7.13 (6ꢀH); δC = 142.8 (Cꢀ
10) ↔ δH = 6.19 (9ꢀH), and δH = 7.13 (6ꢀH); δC = 146.0 (Cꢀ6) ↔
δH = 6.19 (9ꢀH), and δH = 6.62 (10ꢀH); δC = 183.5 (Cꢀ8) ↔ δH =
6.19 (9ꢀH), δH = 6.62 (10ꢀH), and δH = 7.13 (6ꢀH); δC = 197.4
(COMe) ↔ δH = 2.51 (COMe), δH = 6.19 (9ꢀH), and δH = 7.13 (6ꢀ
1645, 1600, 1580, 1270, 1220, 1145, 1115, 1065, 980, 945, 915
cm−1. Elemental analysis: C15H12O4 (256.3); Calcd: C: 70.31%,
H: 4.72%; found: C: 70.09%, H: 4.65%. HRMS (pos. APCI) m/z:
[M + H]+ calcd for C15H13O4, 257.0808; found, 257.0809.
Synthesizing Deslongchamps Adducts:
10
ACS Paragon Plus Environment

Page 11 of 21
The Journal of Organic Chemistry
8'-(tert-Butyl)
4a'-Methyl
(4a'S,5'S,8a'S)-7'-Hydroxy-5'-
4.19 (8aꢀH) and δH = 6.54 (2ꢀH). DQF-COSY ["H,HꢀCOSY specꢀ
trum" (500.32 MHz), CDCl3] [δH(1H) ↔ δH(1H)]: δH = 1.07 (5'ꢀ
H3) ↔ δH = 2.77 (5ꢀH); δH = 2.51 (6ꢀH2) ↔ δH = 2.77 (5ꢀH); δH =
3.73 (1'ꢀH1) ↔ δH = 3.89 (1''ꢀH2); δH = 3.73 (1'ꢀH1) ↔ δH = 4.03
(1'ꢀH2); δH = 3.89 (1''ꢀH2) ↔ δH = 4.03 (1'ꢀH2); δH = 5.98 (3ꢀH) ↔
1
2
3
4
methyl-4'-oxo-6',8a'-dihydro-4'H-spiro(naphthalene-2,1'-
[1,3]dioxolane)-4a',8'(5'H)-dicarboxylate (cis,synꢀ6a)
δH = 6.54 (2ꢀH). IR (CDCl3): ν̃ = 2980, 2890, 1745, 1680, 1640,
5
6
7
8
1400, 1370, 1295, 1235, 1155, 1090, 1075, 1050, 1015, 950 cm−1.
Elemental analysis: C20H26O8 (394.4); Calcd: C: 60.90%, H:
6.64%; found: C: 60.55%, H: 6.59%. HRMS (neg. APCI) m/z:
[M + NH4]+ calcd for C20H30O8N, 412.1966; found, 412.1967.
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
8'-(tert-Butyl)
4a'-Methyl
(4a'S,5'S,8a'S)-7'-Hydroxy-5'-
isobutyl-4'-oxo-6',8a'-dihydro-4'H-spiro(naphthalene-2,1'-
[1,3]dioxolane)-4a',8'(5'H)-dicarboxylate (cis,synꢀ6b)
Cs2CO3 (553 mg, 1.70 mmol, 1.05 equiv.) was added to a solution
of benzoquinone monoketal 5b (340 mg, 1.62 mmol, 1.0 equiv.)
and βꢀketoester 2a (356 mg, 1.94 mmol, 1.2 equiv.) in CH2Cl2
(54 mL) at 25°C in one portion. The reaction mixture was stirred
at 25°C for 3.5 h and filtered through a pad of celite® (2 cm ×
1 cm). The pad was rinsed with EtOAC (75 mL). The solvent was
evaporated and the residue was purified by flash chromatography
on silica gel36 [3 cm × 15 cm, cC6H12:EtOAC 4:1 to 1:1 (v:v),
20 mL] to render the title compound (F5ꢀ24; 593 mg, 93%) as a
1
colorless solid. Melting point: 49ꢀ51°C. H NMR (500.32 MHz,
TMS as internal standard, CDCl3): δ = 1.07 (d, J5',5 = 6.9 Hz, 3H,
5'ꢀH3 of keto), 1.10 (d, J5',5 = 6.9 Hz, 3H, 5'ꢀH3 of enol), 1.46 (s, 9H, 3
× 8''ꢀMeof keto), 1.48 (s, 9H, 3 × 8''ꢀMeof enol), 2.51 (m, 2H, 6ꢀH2 of
enol), 2.77 (m, 1H, 5ꢀHof enol), 3.65 (s, 3H, CO2Meof enol), 3.70 (s,
3H, CO2Meof keto), 3.71ꢀ3.75 (m, 1H, 1'ꢀH1of enol)*, 3.85ꢀ3.93 (m,
2H, 1''ꢀH2 of enol)*, 4.01ꢀ4.05 (m, 1H, 1'ꢀH2of enol)*, 4.19 (s, 1H, 8aꢀ
Cs2CO3 (309 mg, 947 ꢁmol, 1.1 equiv.) was added to a solution of
benzoquinone monoketal 5b (181 mg, 861 ꢁmol, 1.0 equiv.) and
Nazarov reagent 2b (253 mg, 1.12 mmol, 1.3 equiv.) in CH2Cl2
(21 mL) at 25°C in one portion. The mixture was stirred at 25°C
for 3.5 h and filtered through a pad of silica gel (2 cm × 1 cm).
The pad was rinsed with EtOAc (40 mL) and the solvent was
evaporated. The residue was purified by flash chromatography on
silica gel36 [2.5 cm × 15 cm, cC6H12:EtOAc 8:1 to 4:1 (v:v),
20 mL] to render the title compound (F7ꢀ27; 269 mg, 72%) as
colorless needles. Melting point: 103ꢀ105°C. 1H NMR
(400.13 MHz, CDCl3): δ = 0.72 (d, J5'''ꢀH,5''ꢀH = 6.4 Hz, 3H, 5'''ꢀH3
of keto), 0.74 (d, J5'''ꢀH,5''ꢀH = 6.5 Hz, 3H, 5'''ꢀH3 of enol), 0.86 (d, J5''''ꢀ
Hof enol), 5.98 (d, J3,2 = 10.2 Hz, 1H, 3ꢀH of enol), 6.12 (d, J3,2
=
10.4 Hz, 1H, 3ꢀH of keto), 6.54 (d, J2,3 = 10.2 Hz, 1H, 2ꢀH of enol),
6.57 (d, J2,3 = 10.2 Hz, 1H, 2ꢀH of keto), 12.62 (7ꢀOH); *: assignꢀ
ment interchangeable. 13C NMR (125.8 MHz, TMS as internal
standard, CDCl3): δ = 15.9 (Cꢀ5')A, 28.2 (3 × 8''ꢀMe)A, 29.9 (Cꢀ
5)A, 35.2 (Cꢀ6)A, 44.2 (Cꢀ8a)A, 51.8 (CO2Me)A, 61.7 (Cꢀ4a)B, 64.5
(Cꢀ1'')*,A, 66.4 (Cꢀ1')*,A, 81.2 (Cꢀ8'')B, 94.9 (Cꢀ8)B, 104.7 (Cꢀ1)B,
127.2 (Cꢀ3)A, 146.1 (Cꢀ2)A, 169.6 (Cꢀ4a')B, 171.6 (Cꢀ8')B, 175.5
= 6.3 Hz, 3H, 5''''ꢀH3 of keto),0.87 (d, J5''''ꢀH,5''ꢀH = 6.6 Hz, 3H,
H,5''ꢀH
A
(Cꢀ7)B, 197.4 (Cꢀ4)B; the indicated 13C nuclei – they are nonꢀ
5''''ꢀH3 of enol), 1.09 (ddd, Jgem = 13.9 Hz, J5'ꢀH(1),5 = 10.0 Hz, J5'ꢀ
quaternary – were identified in an edHSQC spectrum by their
= 3.8 Hz, 1H, 5'ꢀH1of enol), 1.40ꢀ1.58 (m, 1H, 5ꢀHof enol),
H(1),5''ꢀH
B
crosspeaks with directly bonded protons; the indicated 13C nuꢀ
1.45 (s, 9ꢀH, 3 × CH3 of keto), 1.48 (s, 9ꢀH, 3 × CH3 of enol), 1.78
(ddd, Jgem = 14.1 Hz, J5'ꢀH(2),5 = 10.0 Hz, J5'ꢀH(2),5''ꢀH = 4.2 Hz, 1H,
5'ꢀH1of enol), ABꢀsignal (δA = 2.41, δB = 2.60, JAB = 18.7, , addiꢀ
tionally split by JA,5 = 9.8 Hz, and JB,5 = 7.8 Hz, 6ꢀH2 of enol), 2.71
(dddd, J5ꢀH,5'ꢀH(1) = J5ꢀH,5'ꢀH(2) = 9.9 Hz, J5ꢀH,6ꢀH(B) = 7.7 Hz, J5ꢀH,5'ꢀ
H(1) = 2.9 Hz, 1H, 5ꢀHof enol), 3.72 (ddd, J1'ꢀH(1),1''ꢀH(A) = 8.1 Hz, Jgem
= 7.4 Hz, J1'ꢀH(1),1''ꢀH(B) = 6.2 Hz, 1H, 1'ꢀH1of enol)*, ABꢀsignal (δA =
3.86, δB = 3.91, JAB = 8.1 Hz, additionally split by JA,1'ꢀH(1) = 8.1
Hz, JA,1'H(2) = 6.1 Hz, JB,1'ꢀH(1) = 6.2 Hz, and JB,1'ꢀH(2) = 3.5 Hz, 1''ꢀ
H2 of enol)**, 4.04 (ddd, Jgem = 7.4 Hz, J1'ꢀH(2),1''ꢀH(A) = 6.1 Hz, J1'ꢀ
clei are quaternary and were distinguished in an HMBC spectrum
2
3
4
by their crosspeaks due to J, J and/or J couplings to "remote"
protons; * assignment interchangeable. edHSQC ["shortꢀrange
C,HꢀCOSY spectrum" (125.8/500.32 MHz), CDCl3] [δC(13C) ↔
δH(1H)]: δC = 15.9 (Cꢀ5') ↔ δH = 1.07 (5'ꢀH3); δC = 28.2 (3 × 8''ꢀ
Me) ↔ δH = 2.77 (3 × 8''ꢀMe); δC = 29.9 (Cꢀ5) ↔ δH = 2.77 (5ꢀH);
δC = 35.2 (Cꢀ6) ↔ δH = 2.51 (6ꢀH2); δC = 44.2 (Cꢀ8a) ↔ δH
=
4.19 (8aꢀH); δC = 51.8 (CO2Me) ↔ δH = 3.65 (CO2Me); δC = 64.5
(Cꢀ1'') ↔ δH = 3.89 (1''ꢀH2); δC = 66.4 (Cꢀ1') ↔ δH = 3.73 (1'ꢀH1);
δC = 66.4 (Cꢀ1') ↔ δH = 4.03 (1'ꢀH2); δC = 127.2 (Cꢀ3) ↔ δH =
5.98 (3ꢀH); δC = 146.1 (Cꢀ2) ↔ δH = 6.54 (2ꢀH). HMBC ["longꢀ
range C,HꢀCOSY spectrum" (125.8/500.32 MHz), CDCl3]
[δC(13C) ↔ δH(1H)]: δC = 61.7 (Cꢀ4a) ↔ δH = 1.07 (5'ꢀH3), δH =
2.51 (6ꢀH2), δH = 2.77 (5ꢀH), δH = 4.19 (8aꢀH), and δH = 5.98 (3ꢀ
H); δC = 81.2 (Cꢀ8'') ↔ δH = 2.77 (3 × 8''ꢀMe); δC = 94.9 (Cꢀ8) ↔
δH = 4.19 (8aꢀH), δH = 6.54 (2ꢀH), and δH = 12.62 (7ꢀOH); δC =
104.7 (Cꢀ1) ↔ δH = 3.73 (1'ꢀH1), δH = 3.89 (1''ꢀH2), δH = 4.03 (1'ꢀ
H2), δH = 4.19 (8aꢀH), δH = 5.98 (3ꢀH), and δH = 6.54 (2ꢀH); δC =
169.6 (Cꢀ4a') ↔ δH = 2.77 (5ꢀH), δH = 3.65 (CO2Me), δH = 4.19
(8aꢀH), and δH = 5.98 (3ꢀH); δC = 171.6 (Cꢀ8') ↔ δH = 4.19 (8aꢀ
H); δC = 175.5 (Cꢀ7) ↔ δH = 1.07 (5'ꢀH3), δH = 2.51 (6ꢀH2), δH =
= 3.5 Hz, 1H, 1'ꢀH2of enol)*, 4.17 (s, 1H, 8aꢀH), 5.96 (d,
H(2),1''ꢀH(B)
J3,2 = 10.2 Hz, 1H, 3ꢀHof enol), 6.07 (d, J3,2 = 10.3 Hz, 1H, 3ꢀH of keꢀ
to), 6.53 (d, J2,3 = 10.2 Hz, 1H, 2ꢀHof enol), 6.56 (d, J2,3 = 10.2 Hz,
1H, 2ꢀH of keto), 12.60 (s, 1H, 7ꢀOHof enol);*,** assignment interꢀ
changeable. 13C NMR (100.6 MHz, CDCl3): δ = 21.3 (Cꢀ5''')A,
243.0 (Cꢀ5'''')A, 25.8 (Cꢀ5'')A, 28.3 (3 × CH3)A, 32.9 (Cꢀ5)A, 34.0
(Cꢀ6)A, 40.1 (Cꢀ5')A, 44.4 (Cꢀ8a)A, 52.0 (CO2Me)A, 62.6 (Cꢀ4a)B,
64.7 (Cꢀ1'')A,*, 66.6 (Cꢀ1')A,*, 81.3 (C(CH3)3)B, 95.1 (Cꢀ8)B, 104.9
(Cꢀ1)B, 127.2 (Cꢀ3)A, 146.1 (Cꢀ2)A, 169.9 (Cꢀ4a')B, 171.7 (Cꢀ8')B,
175.8 (Cꢀ7)B, 197.9 (Cꢀ4)B; * assignment interchangeable; the
A
indicated 13C nuclei – they are nonꢀquaternary – were identified in
an edHSQC spectrum by their crosspeaks with directly bonded
protons; B the indicated 13C nuclei are quaternary and were distinꢀ
4.19 (8aꢀH), and δH = 12.62 (7ꢀOH); δC = 197.4 (Cꢀ4) ↔ δH
=
11
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 12 of 21
2
3
guished in an HMBC spectrum by their crosspeaks due to J, J
20 mL] to render the title compound (F5ꢀ22; 90.2 mg, 95%) as
4
pale orange crystals. Melting point: 121ꢀ125°C. 1H NMR
(400.13 MHz, CDCl3): δ = 0.91 (d, J5',5 = 6.8, 3H, 5'ꢀH3 of keto),
1.04 (d, J5',5 = 6.9 Hz, 3H, 5'ꢀH3 of enol), 1.46 (s, 9H, 3 × 8''ꢀMe of keꢀ
to), 1.49 (s, 9H, 3 × 8''ꢀMe of enol), 2.01 [s, 3H, C(=O)Meof enol], 2.51
(mc, 2H, 6ꢀH2 of enol), 2.65ꢀ2.71 (m, 1H, 5ꢀH of enol), 3.74 (ddd, J1'ꢀ
1
2
3
4
5
6
7
8
and/or J couplings to "remote" protons. edHSQC ["shortꢀrange
C,HꢀCOSY spectrum" (100.6/400.13 MHz), CDCl3] [δC(13C) ↔
δH(1H)]: δC = 21.3 (Cꢀ5''') ↔ δH = 0.74 (5'''ꢀH3); δC = 24.0 (Cꢀ
5'''') ↔ δH = 0.87 (5''''ꢀH3); δC = 25.8 (Cꢀ5'') ↔ δH = 1.49 (5''ꢀH);
δC = 28.3 (3 × CH3) ↔ δH = 1.48 (3 × CH3); δC = 32.9 (Cꢀ5) ↔ δH
= 2.71 (5ꢀH); δC = 34.0 (Cꢀ6) ↔ δH = 2.41 (6ꢀHA); δC = 34.0 (Cꢀ
6) ↔ δH = 2.60 (6ꢀHB); δC = 40.1 (Cꢀ5') ↔ δH = 1.09 (5'ꢀH1); δC =
40.1 (Cꢀ5') ↔ δH = 1.78 (5'ꢀH2); δC = 44.4 (Cꢀ8a) ↔ δH = 4.17
(8aꢀH); δC = 52.0 (CO2Me) ↔ δH = 3.64 (CO2Me); δC = 64.7 (Cꢀ
1'') ↔ δH = 3.86 (1''ꢀHA); δC = 64.7 (Cꢀ1'') ↔ δH = 3.91 (1''ꢀHB);
= 8.1 Hz, Jgem = 7.4 Hz, J1'ꢀH(1),1''ꢀH(B) = 6.1 Hz, 1H, 1'ꢀ
H(1),1''ꢀH(A)
H1of enol)*, AB signal (δA = 3.89, δB = 3.93, JAB = 8.1 Hz, A part
additionally split by J1''ꢀH(A),1'ꢀH(1) = 8.1 Hz, J1''ꢀH(A),1'ꢀH(2) = 6.1 Hz,
B part additionally split by J1''ꢀH(B),1'ꢀH(1) = 6.1 Hz, J1''ꢀH(B),1'ꢀH(2)
3.5 Hz, 1''ꢀH2 of enol)*, 4.03 (s, 1H, 8aꢀHof enol) superimposed by
4.05 (ddd, Jgem= 7.4 Hz, J1'ꢀH(2),1''ꢀH(A) = 6.1 Hz, J1'ꢀH(1),1''ꢀH(B)
=
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
=
δC = 66.6 (Cꢀ1') ↔ δH = 3.72 (1'ꢀH1); δC = 66.6 (Cꢀ1') ↔ δH
=
3.4 Hz, 1H, 1'ꢀH2of enol)*, 4.24 (mc, 1H, 1'ꢀH2 of keto)**, 4.37 (mc,
1H, 1''ꢀH2 of keto)**, 6.01 (d, J3,2 = 10.2 Hz, 1H, 3ꢀHof enol), 6.17 (d,
J3,2 = 10.2 Hz, 1H, 3ꢀHof keto), 6.57 (d, J2,3 = 10.2 Hz, 1H, 2ꢀHof
enol), 6.64 (d, J2,3 = 10.1 Hz, 1H, 2ꢀHof keto), 12.49 (s, 1H, 7ꢀOHof
enol); *,** assignment interchangeable. 13C NMR (100.6 MHz,
CDCl3): δ = 16.0 (Cꢀ5')A, 27.3 [C(=O)Me]A, 28.4 (3 × Cꢀ8''Me)A,
30.5 (Cꢀ5)A, 35.4 (Cꢀ6)A, 43.5 (Cꢀ8a)A, 64.7 (Cꢀ1'')*, A, 65.5 (Cꢀ
4a)B, 66.6 (Cꢀ1')*, A, 81.6 (Cꢀ8'')B, 93.9 (Cꢀ8)B, 104.8 (Cꢀ1)B,
127.8 (Cꢀ3)A, 146.3 (Cꢀ2)A, 171.4 (Cꢀ7)B, 176.9 (Cꢀ8')B, 199.5 (Cꢀ
4.04 (1'ꢀH2); δC = 127.2 (Cꢀ3) ↔ δH = 5.96 (3ꢀH); δC = 146.1 (Cꢀ
2) ↔ δH = 6.53 (2ꢀH). HMBC ["longꢀrange C,HꢀCOSY specꢀ
trum" (100.6/400.13 MHz), CDCl3] [δC(13C) ↔ δH(1H)]: δC = 62.6
(Cꢀ4a) ↔ δH = 1.09 (5'ꢀH1), δH = 2.60 (6ꢀHB), δH = 4.17 (8aꢀH),
δH = and 5.96 (3ꢀH); δC = 81.3 (C(CH3)3) ↔ δH = 1.48 (3 × CH3);
δC = 95.2 (Cꢀ8) ↔ δH = 2.41 (6ꢀHA), δH = 2.60 (6ꢀHB), δH = 4.17
(8aꢀH), δH = 6.53 (2ꢀH), and δH = 12.60 (7ꢀOH); δC = 104.9 (Cꢀ1)
↔ δH = 2.41 (6ꢀHA), δH = 3.72 (1'ꢀH1), δH = 3.86 (1''ꢀHA), δH
=
A
4a')B, 203.3 (Cꢀ4)B; *assignment interchangeable; the indicated
3.91 (1''ꢀHB), δH = 4.04 (1'ꢀH2), δH = 4.17 (8aꢀH), δH = 5.96 (3ꢀH),
and δH = 6.53 (2ꢀH); δC = 169.9 (Cꢀ4a') ↔ δH = 2.71 (5ꢀH), δH =
3.64 (CO2Me), δH = 4.17 (8aꢀH), and δH = 5.96 (3ꢀH); δC = 171.7
(Cꢀ8') ↔ δH = 4.17 (8aꢀH); δC = 175.8 (Cꢀ7) ↔ δH = 1.09 (5'ꢀH1),
13C nuclei – they are nonꢀquaternary – were identified in an
edHSQC spectrum by their crosspeaks with directly bonded proꢀ
B
tons; the indicated 13C nuclei are quaternary and were distinꢀ
2
3
δH = 2.41 (6ꢀHA), δH = 2.60 (6ꢀHB), δH = 4.17 (8aꢀH), and δH
=
guished in a HMBC spectrum by their crosspeaks due to J, J
4
and/or J couplings to "remote" protons. edHSQC ["shortꢀrange
12.60 (7ꢀOH); δC = 197.9 (Cꢀ4) ↔ δH = 2.71 (5ꢀH), δH = 4.17 (8aꢀ
H), and δH = 6.53 (2ꢀH). DQF-COSY ["H,HꢀCOSY spectrum"
(400.13 MHz), CDCl3] [δH(1H) ↔ δH(1H)]: δH = 1.49 (5''ꢀH) ↔
δH = 0.74 (5'''ꢀH3), δH = 0.87 (5''''ꢀH3), and δH = 1.09 (5'ꢀH1); δH =
1.78 (5'ꢀH2) ↔ δH = 1.09 (5'ꢀH1) and δH = 1.49 (5''ꢀH); δH = 2.60
(6ꢀHB) ↔ δH = 2.41 (6ꢀHA); δH = 2.71 (5ꢀH) ↔ δH = 1.09 (5'ꢀH1),
δH = 1.78 (5'ꢀH2), δH = 2.41 (6ꢀHA), and δH = 2.60 (6ꢀHB); δH =
3.86 (1''ꢀHA) ↔ δH = 3.72 (1'ꢀH1); δH = 3.91 (1''ꢀHB) ↔ δH = 3.72
(1'ꢀH1); δH = 4.04 (1'ꢀH2) ↔ δH = 3.72 (1'ꢀH1), δH = 3.86 (1''ꢀHA),
and δH = 3.91 (1''ꢀHB); δH = 6.53 (2ꢀH) ↔ δH = 5.96 (3ꢀH). IR
C,HꢀCOSY spectrum" (100.6/400.13 MHz), CDCl3] [δC(13C) ↔
δH(1H)]: δC = 16.0 (Cꢀ5') ↔ δH = 1.04 (5'ꢀH3); δC = 27.3
[C(=O)Me] ↔ δH = 2.01 [C(=O)Me]; δC = 28.4 (3 × Cꢀ8''ꢀMe) ↔
δH = 1.49 (3 × 8''ꢀMe); δC = 30.5 (Cꢀ5) ↔ δH = 2.68 (5ꢀH); δC =
35.4 (Cꢀ6) ↔ δH = 2.51 (6ꢀH2); δC = 43.5 (Cꢀ8a) ↔ δH = 4.03 (8aꢀ
H); δC = 64.7 (Cꢀ1'') ↔ δH = 3.91 (1''ꢀH2); δC = 66.6 (Cꢀ1') ↔ δH
= 3.74 (1'ꢀH1); δC = 66.6 (Cꢀ1') ↔ δH = 4.04 (1'ꢀH2); δC = 127.8
(Cꢀ3) ↔ δH = 6.01 (3ꢀH); δC = 146.3 (Cꢀ2) ↔ δH = 6.57 (2ꢀH).
HMBC ["longꢀrange C,HꢀCOSY spectrum" (100.6/400.13 MHz),
CDCl3] [δC(13C) ↔ δH(1H)]: δC = 65.5 (Cꢀ4a) ↔ δH = 1.04 (5'ꢀ
H3), δH = 2.01 [C(=O)Me], δH = 4.03 (8aꢀH), and δH = 6.01 (3ꢀH);
δC = 81.6 (Cꢀ8'') ↔ δH = 1.49 (8'''ꢀH9); δC = 93.9 (Cꢀ8) ↔ δH =
2.51 (6ꢀH2) and δH = 4.03 (8aꢀH); δC = 104.8 (Cꢀ1) ↔ δH = 4.03
(8aꢀH) and δH = 6.01 (3ꢀH); δC = 171.4 (Cꢀ7) ↔ δH = 4.03 (8aꢀH);
δC = 176.9 (Cꢀ8') ↔ δH = 2.51 (6ꢀH2) and δH = 4.03 (8aꢀH); δC =
199.5 (Cꢀ4a') ↔ δH = 6.57 (2ꢀH); δC = 203.3 (Cꢀ4) ↔ δH = 2.01
[C(=O)Me], δH = 1.04 (5'ꢀH3), and δH = 4.03 (8aꢀH). IR (CDCl3):
(CDCl3): ν̃ = 2950, 1745, 1680, 1640, 1400, 1370, 1300, 1230,
1160, 1100, 1065, 1020, 995, 975, 950 cm−1. Elemental analysis:
C23H32O8 (436.50); Calcd: C 63.29%, H 7.39%; Found:
C 63.15%, H 7.35%.
8'-(tert-Butyl)
(4a'R,5'S,8a'R)-4a'-Acetyl-7'-hydroxy-5'-
methyl-4'-oxo-4a',5',6',8a'-tetrahydro-4'H-spiro(naphthalene-
2,1'-[1,3]dioxolane)-8'-carboxylate (cis,synꢀ6c)
ν̃ = 2920, 2850, 1720, 1675, 1640, 1460, 1365, 1295, 1230, 1145,
1090, 1035, 1005, cm−1. Elemental analysis: C20H26O7 (378.4);
Calcd: C: 63.48%, H: 6.93%; Found: C: 63.10%, H: 7.13%.
HRMS (pos. APCI) m/z: [M + Na]+ calcd for C20H26O7Na,
401.1576; found, 401.1577.
8'-(tert-Butyl)
isobutyl-4'-oxo-4a',5',6',8a'-tetrahydro-4'H-
spiro(naphthalene-2,1'-[1,3]dioxolane)-8'-carboxylate (cis,synꢀ
6d)
(4a'R,5'S,8a'R)-4a'-Acetyl-7'-hydroxy-5'-
Cs2CO3 (85.9 mg, 264 ꢁmol, 1.05 equiv.) was added to the soluꢀ
tion of benzoquinone monoketal 5c (48.4 mg, 249 ꢁmol,
1.0 equiv.) and βꢀketoester 2a (48.4 mg, 263 ꢁmol, 1.05 equiv.) in
CH2Cl2 (4 mL) at 25°C in one portion. The reaction mixture was
stirred at 25°C for 3.5 h and filtered through a pad of silica gel
(2 cm × 1 cm). The pad was rinsed with EtOAc (20 mL). The solꢀ
vent was evaporated and the redisu was purified by flash chromaꢀ
tography an silica gel36 [2 cm × 15 cm, cC6H12:EtOAc 9:1 (v:v),
12
ACS Paragon Plus Environment

Page 13 of 21
The Journal of Organic Chemistry
δH = 0.95 (5'ꢀH1), δH = 2.43 (6ꢀH1), δH = 2.57 (6ꢀH2), δH = 2.61
1
2
3
4
5
6
7
8
9
(5ꢀH), δH = 4.02 (8aꢀH), and δH = 12.49 (OH); δC = 199.9 (Cꢀ4)
↔ δH = 2.61 (5ꢀH), δH = 4.02 (8aꢀH), δH = 5.99 (3ꢀH), and δH =
6.56 (2ꢀH); δC = 203.7 (Cꢀ4a') ↔ δH = 2.43 (6ꢀH1), δH = 2.57 (6ꢀ
H2), δH = 2.61 (5ꢀH), δH = 4.02 (8aꢀH), and δH = 5.99 (3ꢀH).
DQF-COSY ["H,HꢀCOSY spectrum" (500.32 MHz), CDCl3]
[δH(1H) ↔ δH(1H)]: δH = 1.45 (5''ꢀH) ↔ δH = 0.72 (5'''ꢀH3); δH =
1.45 (5''ꢀH) ↔ δH = 0.85 (5''''ꢀH3); δH = 1.45 (5''ꢀH) ↔ δH = 1.76
(5'ꢀH2); δH = 1.76 (5'ꢀH2) ↔ δH = 0.95 (5'ꢀH1); δH = 1.76 (5'ꢀH2)
↔ δH = 1.45 (5''ꢀH); δH = 2.57 (6ꢀH2) ↔ δH = 2.43 (6ꢀH1); δH =
2.61 (5ꢀH) ↔ δH = 0.95 (5'ꢀH1); δH = 2.61 (5ꢀH) ↔ δH = 1.76 (5'ꢀ
H2); δH = 2.61 (5ꢀH) ↔ δH = 2.43 (6ꢀH1); δH = 3.90 (1''ꢀH2) ↔ δH
= 3.72 (1'ꢀH1); δH = 4.06 (1'ꢀH2) ↔ δH = 3.72 (1'ꢀH1); δH = 4.06
(1'ꢀH2) ↔ δH = 3.90 (1''ꢀH2); δH = 6.56 (2ꢀH) ↔ δH = 5.99 (3ꢀH).
Cs2CO3 (282 mg, 0.87 mmol, 1.05 equiv.) was added to a solution
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
of benzoquinone monoketal 5c (160 mg, 0.82 mmol, 1.0 equiv.)
and βꢀketoester 2b (242 mg, 1.07 mmol, 1.3 equiv.) in CH2Cl2
(16 mL) in one portion at 25°C. The reaction mixture was stirred
at 25°C for 2 h and filtered through a pad of celite® (2 cm ×
1 cm). The pad was rinsed with EtOAC (40 mL). The solvent was
evaporated and the residue was purified by flash chromatography
on silica gel36 [2 cm x 15 cm, cC6H12:EtOAC 10:1 to 1:1 (v:v),
20 mL] to render the title compound (F7ꢀ21; 260 mg, 75%) as
colorless solid. Melting point: 134ꢀ136°C. 1H NMR
(500.32 MHz, CDCl3): δ = 0.72 (d, J5''',5'' = 6.5 Hz, 3H, 5'''ꢀH3 of
enol), 0.85 (d, J5'''',5'' = 6.5 Hz, 3H, 5''''ꢀH3 of enol), 0.94ꢀ1.00 (m, 1H,
5'ꢀH1of enol), 1.40ꢀ1.52 (m, 1H, 5''ꢀH of enol), 1.49 (s, 9H, 3 x 8''ꢀMe of
enol), 1.73ꢀ1.79 (m, 1H, 5'ꢀH2of enol), 2.01 (s, 3H, 4a'ꢀMe of enol), 2.04
(s, 3H, 4a'ꢀMe of keto), 2.39ꢀ2.46 (m, 6ꢀH1of enol), 2.54ꢀ2.64 (m, 3H,
5ꢀH and 6ꢀH2of enol), 3.70ꢀ3.74 (m, 1'ꢀH1of enol)*, 3.85ꢀ3.94 (m, 2H,
IR (CDCl3): ν̃ = 2955, 1720, 1675, 1645, 1300, 1220, 1155, 1100,
1030, 975, 950 cm−1. Elemental analysis: C23H32O7 (420.50);
Calcd: C 65.70%, H 7.67%; Found: C 65.60%, H 7.51%.
HRMS (neg. APCI) m/z: [M − H]− calcd for C23H31O7, 419.2075,
found, 419.2077.
8'-(tert-Butyl)
(4a'S,5'S,8a'R)-4a'-Benzoyl-7'-hydroxy-5'-
methyl-4'-oxo-4a',5',6',8a'-tetrahydro-4'H-spiro(naphthalene-
2,1'-[1,3]dioxolane)-8'-carboxylate (cis,synꢀ6e)
1''ꢀH2 of enol)*, 4.02 (s, 1H, 8a'ꢀH of enol), 4.04ꢀ4.08 (m, 1H, 1'ꢀH2
of
enol)*, 5.99 (d, J3,2 = 10.2 Hz, 1H, 3ꢀH enol), 6.12 (d, J3,2
=
of
10.3 Hz, 1H, 3ꢀH of keto), 6.56 (d, J2,3 = 10.2 Hz, 1H, 2ꢀH of enol),
6.63 (d, J2,3 = 10.2 Hz, 1H, 2ꢀH of keto), 12.49 (s, 1H, OH of enol); *:
assignment interchangeable. 13C NMR (125.8 MHz, CDCl3): δ =
21.2 (Cꢀ5''')A, 23.9 (Cꢀ5'''')A, 25.9 (Cꢀ5'')A, 27.2 (Cꢀ4a'ꢀMe)A, 28.4
(Cꢀ8''ꢀMe)A, 33.3 (Cꢀ5)A, 34.0 (Cꢀ6)A, 39.9 (Cꢀ5')A, 43.6 (Cꢀ8a)A,
64.7 (Cꢀ1')A,*, 66.2 (Cꢀ4a)B, 66.7 (Cꢀ1'')A,*, 81.6 (Cꢀ8'')B, 93.9 (Cꢀ
8)B, 104.8 (Cꢀ1)B, 127.7 (Cꢀ3)A, 146.2 (Cꢀ2)A, 171.4 (Cꢀ8')B,
177.1 (Cꢀ7)B, 199.9 (Cꢀ4)B, 203.7 (Cꢀ4a')B; A the indicated 13C nuꢀ
clei – they are nonꢀquaternary – were identified in an edHSQC
Cs2CO3 (85.6 mg, 263 ꢁmol, 1.05 equiv.) was added to a solution
of benzoquinone monoketal 5d (64.1 mg, 250 ꢁmol, 1.0 equiv.)
and βꢀketoester 2a (48.4 mg, 263 ꢁmol, 1.05 equiv.) in CH2Cl2
(4 mL) at 25°C in one portion. The reaction mixture was stirred at
25°C for 3.5 h and filtered through a pad of celite® (2 cm ×
1 cm). The pad was rinsed with EtOAc (20 mL). The solvent was
evaporated and the residue was purified by flash chromatography
on silica gel36 [2 cm × 15 cm, cC6H12:EtOAC 8:1 to 4:1 (v:v),
20 mL] to render the title compound (F9ꢀ20; 78.1 mg, 71%) as
colorless needles. Melting point: 130ꢀ134°C. 1H NMR
(400.13 MHz, CDCl3): δ = 1.10 (s, 9H, 3 × 8''ꢀMe of enol), 1.20 (d,
J5',5 = 6.7, 3H, 5'ꢀH3 of enol), 1.67 (s, 9H, 3 × 8''ꢀMe of keto), 1.80 (d,
J5',5 = 7.3 Hz, 3H, 5'ꢀH3 of keto), AB signal (δA = 2.58, δB = 2.63,
JAB = 18.8 Hz, A part additionally split by J6ꢀH(A),5 = 8.1 Hz, B
part additionally split by J6ꢀH(B),5 = 9.1 Hz, 6ꢀH2 of enol), 2.82 (ddq,
J5,6ꢀH(B) = 9.2 Hz, J5,6ꢀH(A) = 8.3 Hz, J5,5' = 7.0, 1H, 5ꢀHof enol), 3.72
(ddd, J1'ꢀH(1),1''ꢀH(B) = 8.1 Hz, Jgem = 7.4 Hz, J1'ꢀH(1),1''ꢀH(A) = 5.9 Hz,
1H, 1'ꢀH1of enol)*, ABꢀSignal (δA = 3.85, δB = 3.87, A part addiꢀ
tionally split by J1''ꢀH(A),1'ꢀH(1) = 5.8 Hz, J1''ꢀH(A),1'ꢀH(2) = 4.0 Hz, B
B
spectrum by their crosspeaks with directly bonded protons; the
indicated 13C nuclei are quaternary and were distinguished in a
2
3
4
HMBC spectrum by their crosspeaks due to J, J and/or J couꢀ
plings to "remote" protons; * assignment interchangeable.
edHSQC
["shortꢀrange
C,HꢀCOSY
spectrum"
(125.8/500.32 MHz), CDCl3] [δC(13C) ↔ δH(1H)]: δC = 21.2 (Cꢀ
5''') ↔ δH = 0.72 (5'''ꢀH3); δC = 23.9 (Cꢀ5'''') ↔ δH = 0.85 (5''''ꢀH3);
δC = 25.9 (Cꢀ5'') ↔ δH = 1.45 (5''ꢀH); δC = 27.2 (Cꢀ4a'ꢀMe) ↔ δH
= 2.01 (4a'ꢀMe); δC = 28.4 (Cꢀ8''ꢀMe) ↔ δH = 1.49 (3 x 8''ꢀMe); δC
= 33.3 (Cꢀ5) ↔ δH = 2.61 (5ꢀH); δC = 34.0 (Cꢀ6) ↔ δH = 2.43 (6ꢀ
H1); δC = 34.0 (Cꢀ6) ↔ δH = 2.57 (6ꢀH2); δC = 39.9 (Cꢀ5') ↔ δH =
0.95 (5'ꢀH1); δC = 39.9 (Cꢀ5') ↔ δH = 1.76 (5'ꢀH2); δC = 43.6 (Cꢀ
8a) ↔ δH = 4.02 (8aꢀH); δC = 64.6 (Cꢀ1') ↔ δH = 3.72 (1'ꢀH1); δC
= 64.6 (Cꢀ1') ↔ δH = 4.06 (1'ꢀH2); δC = 66.7 (Cꢀ1'') ↔ δH = 3.90
(1''ꢀH2); δC = 127.7 (Cꢀ3) ↔ δH = 5.99 (3ꢀH); δC = 146.2 (Cꢀ2) ↔
δH = 6.56 (2ꢀH). HMBC ["longꢀrange C,HꢀCOSY spectrum"
(125.8/500.32 MHz), CDCl3] [δC(13C) ↔ δH(1H)]: δC = 66.2 (Cꢀ
4a) ↔ δH = 0.95 (5'ꢀH1), δH = 1.76 (5'ꢀH2), δH = 1.76 (5'ꢀH2), δH =
2.01 (4a'ꢀMe), δH = 2.43 (6ꢀH1), δH = 2.57 (6ꢀH2), δH = 2.61 (5ꢀH),
δH = 4.02 (8aꢀH), δH = 5.99 (3ꢀH), and δH = 6.56 (2ꢀH); δC = 81.6
(Cꢀ8'') ↔ δH = 1.49 (3 x 8''ꢀMe); δC = 93.9 (Cꢀ8) ↔ δH = 2.43 (6ꢀ
H1), δH = 2.57 (6ꢀH2), δH = 4.02 (8aꢀH), δH = 6.56 (2ꢀH), and δH =
12.49 (OH); δC = 104.8 (Cꢀ1) ↔ δH = 2.43 (6ꢀH1), δH = 2.57 (6ꢀ
H2), δH = 3.72 (1'ꢀH1), δH = 3.90 (1''ꢀH2), δH = 4.06 (1'ꢀH2), δH =
4.02 (8aꢀH), δH = 5.99 (3ꢀH), and δH = 6.56 (2ꢀH); δC = 171.4 (Cꢀ
8') ↔ δH = 2.57 (6ꢀH2) and δH = 4.02 (8aꢀH); δC = 177.1 (Cꢀ7) ↔
part additionally split by J1''ꢀH(B),1'ꢀH(1) = 8.1 Hz, J1''ꢀH(B),1'ꢀH(2)
5.5 Hz, 2H, 1'ꢀH2 of enol)*, 4.04 (ddd, Jgem = 7.4 Hz, J1'ꢀH(2),1''ꢀH(B)
=
=
5.7 Hz, J1'ꢀH(2),1''ꢀH(A) = 4.2 Hz, 1H, 1'ꢀH2 of enol)*, 4.23 (s, 1H, 4aꢀ
Hof enol), 6.18 (d, J3,2 = 10.3 Hz, 1H, 3ꢀHof enol), 6.66 (d, J2,3
=
10.2 Hz, 1H, 2ꢀHof enol), 6.72 (d, J2,3 = 10.5 Hz, 1H, 2ꢀHof keto),
7.32 (m, 2H, 2 × metaꢀHof enol), 7.46 (m, 1H, paraꢀHof enol), 7.50ꢀ
7.53 (m, 2H, 2 × orthoꢀHof enol), 12.60 (s, 1H, 7ꢀOHof enol);
*assignment interchangeable. 13C NMR (100.6 MHz, CDCl3): δ =
16.3 (Cꢀ5')A, 27.9 (3 × Cꢀ8''ꢀMe)A, 31.8 (Cꢀ5)A, 35.5 (Cꢀ6)A, 44.8
13
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 14 of 21
(Cꢀ8a)A, 63.9 (Cꢀ4a)B, 64.7 (Cꢀ1')*, A, 66.6 (Cꢀ1'')*, A, 80.9 (Cꢀ
gel36 [2 cm × 16 cm, cC6H12:EtOAC 3:1 (v:v), 9 mL] to render
8'')B, 93.9 (Cꢀ8)B, 104.8 (Cꢀ1)B, 127.9 (Cꢀ3)A, 128.3 (2 × Cꢀ
meta)A, 128.9 (2 × Cꢀortho)A, 131.8 (Cꢀpara)A, 136.4 (Cꢀipso)B,
147.0 (Cꢀ2)A, 171.3 (Cꢀ7)B, 176.8 (Cꢀ8')B, 197.6 (Cꢀ4a')B, 199.4
(Cꢀ4)B; *assignment interchangeable; A the indicated 13C nuclei –
they are nonꢀquaternary – were identified in an edHSQC spectrum
1
2
3
4
5
6
7
8
the title compound (F5ꢀ22; 55.1 mg, 71%) as colorless solid.
1
Melting Point: 115ꢀ118°C. H NMR (400.13 MHz, CDCl3): δ =
0.77 (d, J5''',5'' = 6.5 Hz, 3H, 5'''ꢀH3 of enol)*, 0.90 (d, J5'''',5'' = 6.6 Hz,
3H, 5''''ꢀH3 of enol)*, 1.10 (s, 9H, tBuꢀH9 of enol), 1.19 (ddd, J5'ꢀH',5'ꢀH(2)
= 14.2 Hz, J5'ꢀH(1),5''ꢀH = 9.8 Hz, J5'ꢀH(1),5ꢀH = 2.9 Hz, 1H, 5'ꢀH1of enol),
B
by their crosspeaks with directly bonded protons; the indicated
1.50ꢀ1.58 (m, 1H, 5''ꢀHof enol), 1.67 (s, 9H, tBuꢀH9 keto), 1.95
of
13C nuclei are quaternary and were distinguished in a HMBC
(ddd, J5'ꢀH(2),5'ꢀH(1) = 14.2 Hz, J5'ꢀH(2),5''ꢀH = 9.8 Hz, J5'ꢀH(2),5ꢀH
4.4 Hz, 1H, 5'ꢀH2of enol), ABꢀSignal (δA = 2.53 Hz, δB = 2.65 Hz,
JAB = 18.7 Hz additionally split by J6ꢀH(A),5ꢀH = 9.6 Hz, J6ꢀH(B),5ꢀH
7.7 Hz, 2H, 6ꢀH2 enol), 2.74 (ddd, J5ꢀH,6ꢀH(A) = 9.7 Hz, J5,6ꢀ
=
2
3
4
spectrum by their crosspeaks due to J, J and/or J couplings to
"remote" protons. edHSQC ["shortꢀrange C,HꢀCOSY spectrum"
(100.6/400.13 MHz), CDCl3] [δC(13C) ↔ δH(1H)]: δC = 16.3 (Cꢀ
5') ↔ δH = 1.2 (5'ꢀH3); δC = 27.9 (3 × Cꢀ8''ꢀMe) ↔ δH = 1.10 (3 ×
8''ꢀMe); δC = 31.8 (Cꢀ5) ↔ δH = 2.86 (5ꢀH); δC = 35.5 (Cꢀ6) ↔ δH
= 2.60 (6ꢀH2); δC = 44.8 (Cꢀ8a) ↔ δH = 4.23 (8aꢀH); δC = 64.7 (Cꢀ
1'') ↔ δH = 3.86 (1''ꢀH2); δC = 66.6 (Cꢀ1') ↔ δH = 3.73 (1'ꢀHA); δC
= 66.6 (Cꢀ1') ↔ δH = 4.04 (1'ꢀHB); δC = 127.9 (Cꢀ3) ↔ δH = 6.18
(3ꢀH); δC = 128.3 (2 × Cꢀmeta) ↔ δH = 7.34 (2 × metaꢀH); δC =
128.9 (2 × Cꢀortho) ↔ δH = 7.52 (2 × orthoꢀH); δC = 131.8 (Cꢀ
para) ↔ δH = 7.46 (paraꢀH); δC = 147.0 (Cꢀ2) ↔ δH = 6.66 (2ꢀH);
*assignment interchangeable. HMBC ["longꢀrange C,HꢀCOSY
spectrum" (100.6/400.13 MHz), CDCl3] [δC(13C) ↔ δH(1H)]: δC =
63.9 (Cꢀ4a) ↔ δH = 1.20 (5'ꢀH3), δH = 2.60 (6ꢀH2), δH = 4.23 (8aꢀ
H), and δH = 6.18 (3ꢀH); δC = 80.9 (Cꢀ8'') ↔ δH = 1.10 (3 × 8''ꢀ
Me); δC = 93.9 (Cꢀ8) ↔ δH = 1.10 (3 × 8''ꢀMe), δH = 2.60 (6ꢀH2),
δH = 4.23 (8aꢀH), δH = 12.60 (7ꢀOH), and δH = 1.10 (3 × 8''ꢀMe);
δC = 104.8 (Cꢀ1) ↔ δH = 4.23 (8aꢀH) and δH = 6.18 (3ꢀH); δC =
136.4 (Cꢀipso) ↔ δH = 7.34 (2 × metaꢀH); δC = 171.3 (Cꢀ7) ↔ δH
= 4.23 (8aꢀH); δC = 176.8 (Cꢀ8') ↔ δH = 2.60 (6ꢀH2), δH = 4.23
(8aꢀH), and δH = 12.60 (7ꢀOH); δC = 197.6 (Cꢀ4a') ↔ δH = 7.52 (2
× orthoꢀH) and δH = 4.23 (8aꢀH); δC = 199.4 (Cꢀ4) ↔ δH = 4.23
(8aꢀH) and δH = 6.66 (2ꢀH). DQF-COSY ["H,HꢀCOSY spectrum"
(400.13 MHz), CDCl3] [δH(1H) ↔ δH(1H)]: δH = 2.86 (5ꢀH) ↔ δH
= 2.60 (6ꢀH2) and δH = 1.20 (5'ꢀH3); δH =3.90 (1''ꢀH2) ↔ δH = 3.73
(1'ꢀHA); δH =4.04 (1'ꢀHB) ↔ δH = 3.73 (1'ꢀHA), δH = 3.90 (1''ꢀH2);
=
9
of
4
H(B) = 7.6 Hz, J5,5'ꢀH(1) = 2.8 Hz, 1H, 5ꢀHof enol), 3.68ꢀ3.74 (m, 1H,
1'ꢀH1of enol)**, 3.82ꢀ3.89 (m, 2H, 1''ꢀH2 of enol)**, 4.03ꢀ4.07 (m, 1H,
1'ꢀH2of enol)*, 4.22 (s, 1H, 8aꢀHof enol), 6.10 (d, J3,2 = 10.2 Hz, 1H,
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
3ꢀHof keto), 6.15 (d, J3,2 = 10.2 Hz, 1H, 3ꢀHof enol), 6.57 (d, J2,3
=
9.0 Hz, 1H, 2ꢀHof keto), 6.66 (d, J2,3 = 10.2 Hz, 1H, 2ꢀHof enol), 7.32ꢀ
7.36 (m, 2H, metaꢀH2 of enol), 7.43ꢀ7.47 (m, 1H, paraꢀH), 7.50ꢀ7.52
(m, 2H, orthoꢀH2 of enol), 12.60 (s, 1H, 7ꢀOH); *, **, assignment
interchangeable. 13C NMR (100.6 MHz, CDCl3): δ = 21.4 (Cꢀ
5''')A,*, 23.9 (Cꢀ5'''')A,*, 26.2 (Cꢀ5'')A, 27.8 (3 × Cꢀ8''ꢀMe)A, 34.2
(Cꢀ6)A, 34.7 (Cꢀ5)A, 40.2 (Cꢀ5')A, 44.9 (Cꢀ8a)A, 64.7 (Cꢀ1'')A,**,
64.8 (Cꢀ4a)B, 66.7 (Cꢀ1')A,**, 80.9 (Cꢀ8'')B, 93.9 (Cꢀ8)B, 104.9 (Cꢀ
1)B, 127.8 (Cꢀ3)A, 128.3 (Cꢀmeta)A, 128.9 (Cꢀortho)A, 131.8 (Cꢀ
para)A, 136.5 (Cꢀipso)B, 147.0 (Cꢀ2)A, 171.2 (Cꢀ7)B, 177.0 (Cꢀ8')B,
197.9 (Cꢀ4a')B, 199.9 (Cꢀ4)B; A the indicated 13C nuclei – they are
nonꢀquaternary – were indicated in an edHSQC spectrum by their
B
crosspeaks with directly bonded protons; the indicated 13C nuꢀ
clei are quaternary and were distinguished in a HMBC spectrum
2
3
4
by their crosspeaks due to J, J and/or J couplings to "remote"
protons;*, ** assignment interchangeable. edHSQC ["shortꢀrange
C,HꢀCOSY
spectrum"
(100.6/400.13 MHz),
CDCl3]
[δC(13C) ↔ δH(1H)]: δC = 21.4 (Cꢀ5''') ↔ δH = 0.77 (5'''ꢀH3); δC =
23.9 (Cꢀ5'''') ↔ δH = 0.90 (5''''ꢀH3); δC = 26.2 (Cꢀ5'') ↔ δH = 1.54
(5''ꢀH); δC = 27.8 (3 × Cꢀ8''ꢀMe) ↔ δH = 1.10 (3 × 8''ꢀMe); δC =
34.2 (Cꢀ6) ↔ δH = 2.53 (6ꢀHA); δC = 34.2 (Cꢀ6) ↔ δH = 2.65 (6ꢀ
HB); δC = 34.7 (Cꢀ5) ↔ δH = 2.74 (5ꢀH); δC = 40.2 (Cꢀ5') ↔ δH =
1.19(5'ꢀH1); δC = 40.2 (Cꢀ5') ↔ δH = 1.95 (5'ꢀH2); δC = 44.9 (Cꢀ
8a) ↔ δH = 4.22 (8aꢀH); δC = 64.7 (Cꢀ1'') ↔ δH = 3.85 (1''ꢀH2); δC
= 66.7 (Cꢀ1') ↔ δH = 3.71 1'ꢀH1); δC = 66.7 (Cꢀ1') ↔ δH = 4.05
(1'ꢀH2); δC = 127.8 (Cꢀ3) ↔ δH = 6.15 (3ꢀH); δC = 128.3 (Cꢀ
meta) ↔ δH = 7.34 (metaꢀH); δC = 128.9 (Cꢀortho) ↔ δH = 7.51
(orthoꢀH); δC = 131.8 (Cꢀpara) ↔ δH = 7.45 (paraꢀH); δC = 147.0
(Cꢀ2) ↔ δH = 6.66 (2ꢀH). HMBC ["longꢀrange C,HꢀCOSY specꢀ
trum" (100.6/400.13 MHz), CDCl3] [δC(13C) ↔ δH(1H)]: δC = 64.8
(Cꢀ4a) ↔ δH = 1.95 (5'ꢀH2), δH = 2.65 (6ꢀHB), δH = 4.22 (8aꢀH),
and δH = 6.15 (3ꢀH); δC = 80.9 (Cꢀ8'') ↔ δH = 1.10 (3 × 8''ꢀMe);
δC = 93.9 (Cꢀ8) ↔ δH = 2.53 (6ꢀHA), δH = 2.65 (6ꢀHB), δH = 4.22
(8aꢀH), δH = 6.66 (2ꢀH), and δH = 12.60 (7ꢀOH); δC = 104.9 (Cꢀ
1) ↔ δH = 2.53 (6ꢀHA), δH = 3.71 (1'ꢀH1), δH = 4.05 (1'ꢀH2), δH =
4.22 (8aꢀH), δH = 6.15 (3ꢀH), and δH = 6.66 (2ꢀH); δC = 136.5 (Cꢀ
ipso) ↔ δH = 7.34 (metaꢀH); δC = 171.2 (Cꢀ7) ↔ δH = 4.22 (8aꢀ
H); δC = 177.0 (Cꢀ8') ↔ δH = 2.53 (6ꢀHA), δH = 2.65 (6ꢀHB), δH =
4.22 (8aꢀH), and δH = 12.60 (7ꢀOH); δC = 197.9 (Cꢀ4a') ↔ δH =
δH =6.66 (2ꢀH) ↔ δH = 6.18 (3ꢀH); δH =7.46 (paraꢀH) ↔ δH
=
7.34 (metaꢀH); δH =7.52 (orthoꢀH) ↔ δH =7.34 (metaꢀH). IR
(CDCl3): ν̃ = 2980, 1690, 1670, 1640, 1300, 1230, 1160, 1090,
1050, 990, 950 cm−1. HRMS (pos. APCI) m/z: [M + Na]+ calcd
for C25H28O7Na, 463.1733; found, 463.1734.
8'-(tert-Butyl)
(4a'S,5'S,8a'R)-4a'-Benzoyl-7'-hydroxy-5'-
isobutyl-4'-oxo-4a',5',6',8a'-tetrahydro-4'H-
spiro(naphthalene-2,1'-[1,3]dioxolane)-8'-carboxylate (cis,synꢀ
6f)
4.22 (8aꢀH) and δH = 7.51 (orthoꢀH); δC = 199.9 (Cꢀ4) ↔ δH
=
4.22 (8aꢀH) and δH = 6.66 (2ꢀH). DQF-COSY ["H,HꢀCOSY specꢀ
trum" (400.13 MHz), CDCl3] [δH(1H) ↔ δH(1H)]: δH = 0.77 (5'''ꢀ
H3) ↔ δH = 1.54 (5''ꢀH); δH = 0.90 (5''''ꢀH3) ↔ δH = 1.54 (5''ꢀH);
δH = 1.19 (5'ꢀH1) ↔ δH = 1.54 (5''ꢀH) and δH = 1.95 (5'ꢀH2); δH =
1.95 (5'ꢀH2) ↔ δH = 2.74 (5ꢀH); δH = 2.53 (6ꢀHA) ↔ δH = 2.65 (6ꢀ
HB) and δH = 2.74 (5ꢀH); δH = 2.65 (6ꢀHB) ↔ δH = 2.74 (5ꢀH); δH
= 6.15 (3ꢀH) ↔ δH = 6.66 (2ꢀH); δH = 7.34 (metaꢀH) ↔ δH = 7.45
Cs2CO3 (56.5 mg, 173 ꢁmol, 1.05 equiv.) was added to a solution
of benzoquinone monoketal 5d (42.3 mg, 165 ꢁmol, 1 equiv.) and
βꢀketoester 2b (36.8 mg, 173 ꢁmol, 1.05 equiv.) in CH2Cl2 (6 mL)
at 25°C in one portion. The reaction mixture was stirred at 25°C
for 22 h and filtered through a pad of celite® (2 cm × 1 cm). The
pad was rinsed with EtOAC (15 mL). The solvent was evaporated
and the residue was purified by flash chromatography on silica
(paraꢀH) and δH = 7.51 (orthoꢀH). IR: (CH2Cl2): ν
̃
= 2445, 1690,
14
ACS Paragon Plus Environment

Page 15 of 21
The Journal of Organic Chemistry
1670, 1640, 1300, 1250, 1230, 1155, 1090, 1025, 985, 950 cm−1.
δH = 2.04 (8ꢀH1) and δH = 2.53 (8ꢀH2); δH = 4.19 (1''ꢀH2) ↔ δH =
HRMS (pos. APCI) m/z: [M + Na]+ calcd for C28H34O7Na,
2.85 (1'ꢀH1); δH = 6.54 (2ꢀH) ↔ δH = 6.01 (3ꢀH). IR (Film): υ =
2935, 1730, 1695, 1680, 1520, 1245, 1185, 1120, 1055, 1020,
940, 915 cmꢀ1. HRMS (pos. APCI) m/z: [M + Na]+ calcd for
C15H18O6Na, 317.0996; found, 317.0997.
1
2
3
4
505.2202; found, 505.2205.
Methyl
(4a'S,5'S,8a'S)-5'-Methyl-4',7'-dioxo-6',7',8',8a'-
tetrahydro-4'H-spiro(naphthalene-2,1'-[1,3]dioxolane)-
4a'(5'H)-carboxylate (cis,synꢀ7a)
5
Methyl
(4a'S,5'S,8a'S)-5'-isobutyl-4',7'-dioxo-6',7',8',8a'-
6
7
8
tetrahydro-4'H-spiro(naphthalene-2,1'-[1,3]dioxolane)-
4a'(5'H)-carboxylate (cis,synꢀ7b)
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
At 0°C F3CCO2H (1 mL) was added dropwise to the solution of
Deslongchamps adduct cis,synꢀ6a (40.6 mg, 103 ꢁmol, 1 equiv.)
in CH2Cl2 (4 mL) within 5 min and stirring was continued at 0°C
for 2 h. The solvent was removed and F3CCO2H was removed
azeotropically with C6H6 (3 × 4 mL) under reduced pressure. The
remaining solid was dissolved in C6H6 (4 mL) and stirred at room
temp. for 8 d. The solvent was evaporated and the residue was puꢀ
rified by flash chromatography on silica gel36 [2 cm × 15 cm,
cC6H12:EtOAc 8:1 to 1:1 (v:v), 20 mL] to render the title comꢀ
At 0°C F3CCO2H (1 mL) was added dropwise to a solution of the
Deslongchamps adduct cis,synꢀ6b (45.0 mg, 0.10 mmol,
1.0 equiv.) in CH2Cl2 (4 mL) within 5 min. The mixture was
stirred at 0°C for 2 h. The solvent was removed and F3CCO2H
was removed azeotropically with C6H6 (3 × 4 mL) under reduced
pressure. The remaining solid was dissolved in C6H6 (4 mL) and
stirred at room temp. for 8 d. The solvent was evaporated and the
residue was purified by flash chromatography on silica gel36
[2 cm × 15 cm, cC6H12:EtOAc 8:1 to 1:1 (v:v), 20 mL] to render
pound (F36ꢀ50; 22.8 mg, 75%) as colorless solid. Melting point:
1
87ꢀ94°C. H NMR (400.13 MHz, CDCl₃): δ = 1.12 (d, J5',5
6.6 Hz, 3H, 5'ꢀH3), 2.04 (dd, J8ꢀH(1),8ꢀH(2) = 16.4 Hz, J8ꢀH(1),8a
5.9 Hz, 1H, 8ꢀH1), 2.44 (ddd, J6ꢀH(1),6ꢀH(2) = 15.2 Hz, J6ꢀH(1),5
4.1 Hz, J6ꢀH(1),8ꢀH(2) = 1.9 Hz, 1H, 6ꢀH1), 2.53 (ddd, J8ꢀH(2),8ꢀH(1)
=
=
=
=
1
the title compound (F30ꢀ38; 25.9 mg, 75%) as colorles oil. H
NMR (400.13 MHz, CDCl₃): δ = 0.70 (d, J5''',5'' = 6.4 Hz, 3H, 5'''ꢀ
H3), 0.85 (d, J5'''',5'' = 6.6 Hz, 3H, 5''''ꢀH3), 1.22 (ddd, J5'ꢀH(1),5'ꢀH(2)
=
16.4 Hz, J8ꢀH(2),6ꢀH(1) = J8ꢀH(2), 8a = 2.3 Hz, 1H, 8ꢀH2), 2.71ꢀ2.78 (m,
1H, 6ꢀH2), 2.77ꢀ2.85 (m, 1H, 5ꢀH), 3.41 (dd, J8a,8ꢀH(1) = 5.8 Hz,
J8a,8ꢀH(2) = 2.6 Hz, 1H, 8aꢀH), 3.77 (s, 3H, CO2Me), 3.82ꢀ3.89 (m,
1H, 1'ꢀH1)*, 3.95ꢀ4.03 (m, 2H, 1'ꢀH2 and 1''ꢀH1)*, 4.15ꢀ4.20 (m,
14.2 Hz, J5'ꢀ(1),6 = 9.9 Hz, J5'ꢀH(1),5 = 2.3 Hz, 1H, 5'ꢀH1), 1.39ꢀ1.50
(m, 1H, 5''ꢀH), 1.67 (ddd, J5'ꢀH(2),5'ꢀH(1) = 14.2 Hz, J5'ꢀH(2),5 = 9.0 Hz,
J5'ꢀH(2),5' = 4.3 Hz, 1H, 5'ꢀH2), 2.01 (dd, J8ꢀH(1),8ꢀH(2) = 16.4 Hz, J8ꢀ
= 5.8 Hz, 1H, 8ꢀH1), 2.54 [ddd, J8ꢀH(2),8ꢀH(1) = 16.6 Hz, J8ꢀ
1H, 1''ꢀH2)*, 6.01 (d, J3,2 = 10.2 Hz, 1H, 3ꢀH), 6.54 (d, J2,3
=
H(1),8a
H(2),8a = 2.4 Hz, 4J8ꢀH(2),6 = 1.4 Hz (the existence of this 4ꢀbond Wꢀ
coupling indicates an equatorial position of this 8ꢀH), 1H, 8ꢀH2],
2.58 (m, 2H, 6ꢀH2), 2.67 (dddd, J5,6 = 18.6 Hz, J5,5'ꢀH(2) = 9.6 Hz,
10.2 Hz, 1H, 2ꢀH);* assignment interchangeable. 13C NMR
(100.6 MHz, CDCl₃): δ = 16.4 (Cꢀ5')A, 33.6 (Cꢀ5)A, 37.5 (Cꢀ8)A,
45.5 (Cꢀ6)A, 46.5 (Cꢀ8a)A, 52.5 (CO2Me)A, 61.6 (Cꢀ4a)B, 64.8 (Cꢀ
1'')A,*, 65.9 (Cꢀ1')A,*, 104.3 (Cꢀ1)B, 127.5 (Cꢀ3)A, 143.7 (Cꢀ2)A,
170.1 (CO2Me)B, 196.1 (Cꢀ4)B, 207.2 (Cꢀ7)B; * assignment interꢀ
changeable; A the indicated 13C nuclei – they are nonꢀquaternary –
were identified in an edHSQC spectrum by their crosspeaks with
J5,6 = 7.3 Hz, J5,5'ꢀH(1) = 2.2 Hz, 1H, 5ꢀH), 3.42 (dd, J8a,8ꢀH(1)
=
5.8 Hz, J8a,8ꢀH(2) = 2.3 Hz, 1H, 8aꢀH), 3.77 (s, 3H, CO2Me), 3.82ꢀ
3.56 (m, 1H, 1'ꢀH1)*, 3.95ꢀ4.00 (m, 1H, 1''ꢀH1)**, 4.00ꢀ4.04 (m,
1H, 1'ꢀH2)*, 4.17ꢀ4.22 (m, 1H, 1''ꢀH2)**, 5.98 (d, J3,2 = 10.2 Hz,
1H, 3ꢀH), 6.54 (d, J2,3 = 10.3 Hz, 1H, 2ꢀH); *,** assignment interꢀ
changeable. 13C NMR (100.6 MHz, CDCl₃): δ = 21.3 (Cꢀ5''')A,
23.8 (Cꢀ5'''')A, 25.9 (Cꢀ5'')A, 36.6 (Cꢀ5)A, 37.5 (Cꢀ8)A, 39.8 (Cꢀ
5')A, 43.7 (Cꢀ6)A, 46.6 (Cꢀ8a)A, 52.6 (CO2Me)A, 62.5 (Cꢀ4a)B,
64.8 (Cꢀ1'')A,*, 66.0 (Cꢀ1')A,*, 104.4 (Cꢀ1)B, 127.3 (Cꢀ3)A, 143.6
B
directly bonded protons; the indicated 13C nuclei are quaternary
and were distinguished in an HMBC spectrum by their crosspeaks
2
3
4
due to J, J and/or J couplings to "remote" protons. edHSQC
["shortꢀrange C,HꢀCOSY spectrum" (100.6/400.13 MHz), CDCl₃]
[δC(13C) ↔ δH(1H)]: δC = 16.4 (Cꢀ5') ↔ δH = 1.12 (5'ꢀH3); δC =
33.6 (Cꢀ5) ↔ δH = 2.81 (5ꢀH); δC = 37.5 (Cꢀ8) ↔ δH = 2.04 (8ꢀ
H1); δC = 37.5 (Cꢀ8) ↔ δH = 2.53 (8ꢀH2); δC = 45.5 (Cꢀ6) ↔ δH =
2.44 (6ꢀH1); δC = 45.5 (Cꢀ6) ↔ δH = 2.74 (6ꢀH2); δC = 46.5 (Cꢀ8a)
↔ δH = 3.41 (8aꢀH); δC = 52.5 (CO2Me) ↔ δH = 3.77 (CO2Me),
δC = 64.8 (Cꢀ1'') ↔ δH = 3.99 (1''ꢀH1); δC = 64.8 (Cꢀ1'') ↔ δH =
4.19 (1''ꢀH2); δC = 65.9 (Cꢀ1') ↔ δH = 2.85 (1'ꢀH1); δC = 65.9 (Cꢀ
1') ↔ δH = 3.99 (1'ꢀH2); δC = 127.5 (Cꢀ3) ↔ δH = 6.01 (3ꢀH); δC =
143.7 (Cꢀ2) ↔ δH = 6.54 (2ꢀH). HMBC ["longꢀrange C,HꢀCOSY
spectrum" (100.6/400.13 MHz), CDCl₃] [δC(13C) ↔ δH(1H)]: δC =
104.3 (Cꢀ1) ↔ δH = 2.04 (8ꢀH1), δH = 3.41 (8aꢀH), δH = 3.99 (1''ꢀ
H1), δH = 3.99 (1'ꢀH2), δH = 4.19 (1''ꢀH2), and δH = 6.01 (3ꢀH); δC
= 170.1 (CO2Me) ↔ δH = 2.81 (5ꢀH), δH = 3.41 (8aꢀH), and δH =
(Cꢀ2)A, 170.3 (CO2Me)B, 196.5 (Cꢀ4)B, 207.3 (Cꢀ7)B; *assignment
A
interchangeable;
the indicated 13C nuclei – they are nonꢀ
quaternary – were identified in an edHSQC spectrum by their
B
crosspeaks with directly bonded protons; the indicated 13C nuꢀ
clei are quaternary and were distinguished in an HMBC spectrum
2
3
4
by their crosspeaks due to J, J and/or J couplings to "remote"
protons. edHSQC ["shortꢀrange C,HꢀCOSY spectrum"
(100.6/400.13 MHz), CDCl₃] [δC(13C) ↔ δH(1H)]: δC = 21.3 (Cꢀ
5''') ↔ δH = 0.70 (5'''ꢀH3); δC = 23.8 (Cꢀ5'''') ↔ δH = 0.85 (5''''ꢀH3);
δC = 25.9 (Cꢀ5'') ↔ δH = 1.44 (5''ꢀH); δC = 36.6 (Cꢀ5) ↔ δH = 2.68
(5ꢀH); δC = 37.5 (Cꢀ8) ↔ δH = 2.01 (8ꢀH1); δC = 37.5 (Cꢀ8) ↔ δH
= 2.54 (8ꢀH2); δC = 39.8 (Cꢀ5') ↔ δH = 1.22 (5'ꢀH1); δC = 39.8 (Cꢀ
5') ↔ δH = 1.67 (5'ꢀH2); δC = 43.7 (Cꢀ6) ↔ δH = 2.58 (6ꢀH2); δC =
46.6 (Cꢀ8a) ↔ δH = 3.42 (8aꢀH); δC = 52.6 (CO2Me) ↔ δH = 3.77
(CO2Me); δC = 64.8 (Cꢀ1'') ↔ δH = 3.98 (1''ꢀH1); δC = 64.8 (Cꢀ
1'') ↔ δH = 4.19 (1''ꢀH2); δC = 66.0 (Cꢀ1') ↔ δH = 3.84 (1'ꢀH1); δC
= 66.0 (Cꢀ1') ↔ δH = 4.02 (1'ꢀH2); δC = 127.3 (Cꢀ3) ↔ δH = 5.98
(3ꢀH); δC = 143.6 (Cꢀ2) ↔ δH = 6.54 (2ꢀH). HMBC ["longꢀrange
C,HꢀCOSY spectrum" (100.6/400.13 MHz), CDCl₃] [δC(13C) ↔
3.77 (CO2Me); δC = 196.1 (Cꢀ4) ↔ δH = 2.53 (8ꢀH2) and δH
=
6.54 (2ꢀH); δC = 207.2 (Cꢀ7) ↔ δH = 2.04 (8ꢀH1), δH = 2.53 (8ꢀ
H2), δH = 2.81 (5ꢀH), δH = 3.41 (8aꢀH), and δH = 3.77 (CO2Me).
DQF-COSY ["H,HꢀCOSY spectrum" (400.13 MHz), CDCl3]
[δH(1H) ↔ δH(1H)]: δH = 2.53 (8ꢀH2) ↔ δH = 2.04 (8ꢀH1); δH
=
2.74 (6ꢀH2) ↔ δH = 2.44 (6ꢀH1); δH = 2.81 (5ꢀH) ↔ δH = 1.12 (5'ꢀ
H3), δH = 2.44 (6ꢀH1), and δH = 2.74 (6ꢀH2); δH = 3.41 (8aꢀH) ↔
15
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 16 of 21
δH(1H)]: δC = 62.5 (Cꢀ4a) ↔ δH = 1.22 (5'ꢀH1), δH = 2.54 (8ꢀH2),
↔ δH = 3.20 (8aꢀH); δC = 45.5 (Cꢀ6) ↔ δH = 2.40 (6ꢀH1); δC =
45.5 (Cꢀ6) ↔ δH = 2.86 (6ꢀH2); δC = 64.9 (Cꢀ1'') ↔ δH = 4.01 (1''ꢀ
1
2
3
4
5
6
7
8
δH = 2.58 (6ꢀH2), δH = 3.42 (8aꢀH), and δH = 5.98 (3ꢀH); δC
=
104.4 (Cꢀ1) ↔ δH = 2.01 (8ꢀH1), δH = 3.42 (8aꢀH), δH = 3.84 (1'ꢀ
HA); δC = 64.9 (Cꢀ1'') ↔ δH = 4.18 (1''ꢀHB); δC = 65.9 (Cꢀ1') ↔ δH
= 3.86 (1'ꢀHA); δC = 65.9 (Cꢀ1') ↔ δH = 4.01 (1'ꢀHB); δC = 128.1
(Cꢀ3) ↔ δH = 6.05 (3ꢀH); δC = 144.2 (Cꢀ2) ↔ δH = 6.59 (2ꢀH).
HMBC ["longꢀrange C,HꢀCOSY spectrum" (125.8/500.32 MHz),
CDCl3] [δC(13C) ↔ δH(1H)]: δC = 65.2 (Cꢀ4a) ↔ δH = 1.00 (5ꢀH),
δH = 1.98 (8ꢀH1), δH = 2.13 (COMe), δH = 2.40 (6ꢀH1), δH = 2.49
(8ꢀH2), δH = 2.66 (5'ꢀH3), δH = 2.86 (6ꢀH2), δH = 3.20 (8aꢀH), and
δH = 6.05 (3ꢀH), δC = 104.2 (Cꢀ1) ↔ δH = 1.98 (8ꢀH1), δH = 3.20
(8aꢀH), δH = 3.86 (1'ꢀHA), δH = 4.01 (1''ꢀHA, 1'ꢀHB), δH = 4.18 (1''ꢀ
HB), and δH = 6.05 (3ꢀH), δC = 198.3 (Cꢀ4) ↔ δH = 2.66 (5'ꢀH3),
δH = 3.20 (8aꢀH), and δH = 6.59 (2ꢀH), δC = 204.7 (COMe) ↔ δH
H1), δH = 3.98 (1''ꢀH1), δH = 4.02 (1'ꢀH2), δH = 4.19 (1''ꢀH2), δH =
5.98 (3ꢀH), and δH = 6.54 (2ꢀH); δC = 170.3 (CO2Me) ↔ δH
=
3.42 (8aꢀH); δC = 196.5 (Cꢀ4) ↔ δH = 6.54 (2ꢀH); δC = 207.3 (Cꢀ
7) ↔ δH = 2.01 (8ꢀH1), δH = 2.54 (8ꢀH2), δH = 2.58 (6ꢀH2), and δH
=
3.42 (8aꢀH). DQF-COSY ["H,HꢀCOSY spectrum"
(400.13 MHz), CDCl3] [δH(1H) ↔ δH(1H)]: δH = 0.85 (5''''ꢀH3) ↔
δH = 0.70 (5'''ꢀH3); δH = 1.44 (5''ꢀH) ↔ δH = 0.70 (5'''ꢀH3), δH
0.85 (5''''ꢀH3), and δH = 1.22 (5'ꢀH1); δH = 1.67 (5'ꢀH2) ↔ δH
=
=
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
1.22 (5'ꢀH1) and δH = 1.44 (5''ꢀH); δH = 2.54 (8ꢀH2) ↔ δH = 2.01
(8ꢀH1); δH = 2.68 (5ꢀH) ↔ δH = 1.22 (5'ꢀH1), δH = 1.67 (5'ꢀH2),
and δH = 2.58 (6ꢀH2); δH = 3.42 (8aꢀH) ↔ δH = 2.01 (8ꢀH1) and δH
= 2.54 (8ꢀH2); δH = 4.19 (1''ꢀH2) ↔ δH = 3.84 (1'ꢀH1); δH = 6.54
(2ꢀH) ↔ δH = 5.98 (3ꢀH). IR (Film): υ = 2955, 1745, 1715, 1680,
1240, 1150, 1120, 1110, 1065, 1020, 980, 970, 915, 930, 915 cmꢀ
1. HRMS (pos. ESI) m/z: [M + Na]+ calcd for C18H24O6Na,
359.1465; found, 359.1467.
= 2.66 (5'ꢀH3) and δH = 3.20 (8aꢀH), δC = 207.3 (Cꢀ7) ↔ δH
=
1.00 (5ꢀH), δH = 1.98 (8ꢀH1), δH = 2.40 (6ꢀH1), δH = 2.49 (8ꢀH2),
δH = 2.86 (6ꢀH2), and δH = 3.20 (8aꢀH). DQF-COSY ["H,Hꢀ
COSY spectrum" (500.32 MHz), CDCl3] [δH(1H) ↔ δH(1H)]: δH =
2.49 (8ꢀH2) ↔ δH = 1.98 (8ꢀH1); δH = 2.66 (5ꢀH) ↔ δH = 1.00 (5'ꢀ
H3) and δH = 2.40 (6ꢀH1); δH = 2.86 (6ꢀH2) ↔ δH = 2.40 (6ꢀH1)
and δH = 2.66 (5ꢀH); δH = 3.20 (8aꢀH) ↔ δH = 1.98 (8ꢀH1) and δH
= 2.49 (8ꢀH2); δH = 4.01 (1''ꢀHA, 1'ꢀHB) ↔ δH = 3.86 (1'ꢀHA); δH =
4.18 (1''ꢀHB) ↔ δH = 3.86 (1'ꢀHA) and δH = 4.01 (1''ꢀHA, 1'ꢀHB);
δH = 6.59 (2ꢀH) ↔ δH = 6.05 (3ꢀH). IR (Film): υ = 2940, 1715,
1670, 1265, 1210, 1145, 1120, 1100, 1020, 990, 985, 975, 950,
910 cmꢀ1. HRMS (pos. APCI) m/z: [M + H]+ calcd for C15H19O5,
279.1227; found, 279.1229.
(4a'R,5'S,8a'S)-4a'-Acetyl-5'-methyl-5',6',8',8a'-tetrahydro-
4'H-spiro(naphthalene-2,1'-[1,3]dioxolane)-4',7'(4a'H)-dione
(cis,synꢀ7c)
(4a'R,5'S,8a'S)-4a'-Acetyl-5'-isobutyl-5',6',8',8a'-tetrahydro-
4'H-spiro(naphthalene-2,1'-[1,3]dioxolane)-4',7'(4a'H)-dione
(cis,synꢀ7d)
At 0°C F3CCO2H (1 mL) was added dropwise to a solution of the
Deslongchamps adduct cis,synꢀ6c (39.0 mg, 0.10 mmol,
1.0 equiv.) in CH2Cl2 (4 mL) within 5 min. The mixture was
stirred at 0°C for 2 h. The solvent was removed and F3CCO2H
was removed azeotropically with C6H6 (3 × 4 mL) under reduced
pressure. The remaining solid was dissolved in C6H6 (4 mL) and
stirred at room temp. for 8 d. The solvent was evaporated and the
residue was purified by flash chromatography on silica gel36
[2 cm × 15 cm, cC6H12:EtOAc 8:1 to 1:1 (v:v), 20 mL] to render
the title compound (F40ꢀ50; 25.7 mg, 90%) as colorless solid.
At room temp. F3CCO2H (0.8 mL) was added dropwise to a soluꢀ
tion of the Deslongchamps adduct cis,synꢀ6d (65.6 mg,
0.16 mmol, 1.0 equiv.) in CH2Cl2 (3.1 mL) within 5 min and the
mixture was stirred at room temp. for 2 h. The solvent was reꢀ
moved and F3CCO2H was removed azeotropically with C6H6 (3 ×
1.5 mL) under reduced pressure. The remaining solid was disꢀ
solved in C6H6 (1.6 mL) and heated under reflux for 4 h. The solꢀ
vent was evaporated and the residue was purified by flash chroꢀ
matography on silica gel36 [2 cm × 20 cm, cC6H12:EtOAc 4:1 to
2:1 (v:v), 20 mL] to render the title compound (F22ꢀ43; 26.5 mg,
1
Melting point: 132ꢀ136°C. H NMR (500.32 MHz, CDCl3): δ =
1.00 (d, J5',5 = 6.8 Hz, 3H, 5'ꢀH3), 1.98 (dd, Jgem = 16.3 Hz, J8ꢀ
= 5.7 Hz, 1H, 8ꢀH1), 2.13 (s, 3H, COMe), 2.40 (ddd, Jgem
=
H(1),8a
4
16.2 Hz, J6ꢀH(1),5 = 5.4 Hz, J6ꢀH(1),8ꢀH(2) = 1.9 Hz, 1H, 6ꢀH1), 2.49
(ddd, Jgem = 16.3 Hz, J8ꢀH(2),8a = 2.9 Hz, 4J8ꢀH(2),6ꢀH(1) = 2.0 Hz, 1H,
8ꢀH2), 2.61ꢀ2.70 (m, 1H, 5ꢀH), 2.86 (dd, Jgem = 16.3 Hz, J6ꢀH(2),5
=
11.6 Hz, 1H, 6ꢀH2), 3.20 (dd, J8a,8ꢀH(1) = 5.7 Hz, J8a,8ꢀꢀH(2) = 3.0 Hz,
1H, 8aꢀH), 3.84ꢀ3.89 (m, 1H, 1'ꢀHA)*, 3.98ꢀ4.04 (m, 2H, 1'ꢀHB,
1''ꢀHA)*,**, 4.16ꢀ4.20 (m, 1H, 1''ꢀHB)**, 6.05 (d, J3,2 = 10.2 Hz, 1H,
3ꢀH), 6.59 (d, J2,3 = 10.3 Hz, 1H, 2ꢀH);*,**, assignment interꢀ
changeable. 13C NMR (125.8 MHz, CDCl3): δ = 16.1 (Cꢀ5')A,
28.2 (COMe)A, 33.9 (Cꢀ5)A, 36.8 (Cꢀ8)A, 44.9 (Cꢀ8a)A, 45.5 (Cꢀ
6)A, 64.9 (Cꢀ1'')*, A, 65.2 (Cꢀ4a)B, 65.9 (Cꢀ1')**, A, 104.2 (Cꢀ1)B,
128.1 (Cꢀ3)A, 144.2 (Cꢀ2)A, 198.3 (Cꢀ4)B, 204.7 (COMe)B, 207.3
1
53%) as colorless solid. Melting point: 168ꢀ170°C. H NMR
(500.32 MHz, CDCl3): δ = 0.68 (d, J5''',5'' = 6.6 Hz, 3H, 5'''ꢀH3),
0.83 (d, J5'''',5'' = 6.6 Hz, 3H, 5''''ꢀH3), 1.10 (ddd, Jgem = 14.1 Hz, J5'ꢀ
H(1),5'' = 9.9 Hz, J5'ꢀH(1),5 = 2.3 Hz, 1H, 5'ꢀH1), 1.37ꢀ1.42 (m, 1H, 5ꢀ
H), 1.56 (ddd, Jgem = 14.0 Hz, J5'ꢀH(2),5 = 9.4 Hz, J5'ꢀH(1),5'' = 4.4 Hz,
1H, 5'ꢀH2), 1.94 (dd, Jgem = 16.3 Hz, J8ꢀH(1),8a = 5.6 Hz, 1H, 8ꢀH1),
2.13 (s, 3H, COMe), 2.48ꢀ2.58 (m, 3H, 8ꢀH2, 6ꢀHA, 5ꢀH), 2.74
(dd, Jgem = 17.8 Hz, J6ꢀH(B),5 = 13.0 Hz, 1H, 6ꢀH2), 3.22 (dd, J8a,8ꢀ
A
(Cꢀ7)B; the indicated 13C nuclei – they are nonꢀquaternary –
were identified in an edHSQC spectrum by their crosspeaks with
B
directly bonded protons; the indicated 13C nuclei are quaternary
= 5.7 Hz, J8a,8ꢀH(2) = 2.7 Hz, 1H, 8aꢀH), 3.82ꢀ3.88 (m, 1H, 1'ꢀ
H(1)
HA)*, 3.99ꢀ4.04 (m, 2H, 1'ꢀHB, 1''ꢀHA)*,**, 4.16ꢀ4.22 (m, 1H, 1''ꢀ
HB)**, 6.02 (d, J3,2 = 10.3 Hz, 1H, 3ꢀH), 6.59 (d, J2,3 = 10.2 Hz,
1H, 2ꢀH); *,** assignment interchangeable. 13C NMR (125.8 MHz,
CDCl3): δ = 21.2 (Cꢀ5''')A, 23.8 (Cꢀ5'''')A, 25.8 (Cꢀ5'')A, 28.1
(COMe)A, 36.8 (Cꢀ5)A, 36.8 (Cꢀ8)A, 39.5 (Cꢀ5')A, 43.6 (Cꢀ6)A,
45.2 (Cꢀ8a)A, 64.9 (Cꢀ1'')A,*, 66.0 (Cꢀ4a)B, 66.1 (Cꢀ1')A,**, 104.3
(Cꢀ1)B, 127.9 (Cꢀ3)A, 144.0 (Cꢀ2)A, 198.7 (Cꢀ4)B, 205.0 (COMe)B,
and were distinguished in an HMBC spectrum by their crosspeaks
2
3
4
* **
due to J, J and/or J couplings to "remote" protons; , assignꢀ
ment interchangeable. edHSQC ["shortꢀrange C,HꢀCOSY specꢀ
trum" (125.8/500.32 MHz), CDCl3] [δC(13C) ↔ δH(1H)]: δC = 16.1
(Cꢀ5') ↔ 1.00 (5'ꢀH3); δC = 28.2 (COMe) ↔ δH = 2.13 (COMe);
δC = 33.9 (Cꢀ5) ↔ δH = 2.66 (5ꢀH); δC = 36.8 (Cꢀ8) ↔ δH = 1.98
(8ꢀH1); δC = 36.8 (Cꢀ8) ↔ δH = 2.49 (8ꢀH2); δC = 44.9 (Cꢀ8a)
16
ACS Paragon Plus Environment

Page 17 of 21
The Journal of Organic Chemistry
* **
207.3 (Cꢀ7)B; , assignment interchangeable; A the indicated 13C
1.45 (d, J5',5 = 6.9 Hz, 3H, 5'ꢀH3), 1.88 (dd, Jgem = 16.4 Hz, J8ꢀ
= 5.8 Hz, 1H, 8ꢀH1), 2.40 (ddd, Jgem = 16.4 Hz, J8ꢀH(2),8a
=
=
1
2
3
4
5
6
7
8
nuclei – they are nonꢀquaternary – were identified in an edHSQC
H(1),8a
B
4
spectrum by their crosspeaks with directly bonded protons; the
2.2 Hz, J8ꢀH(2),6ꢀH(1) = 2.2 Hz, 1H, 8ꢀH2), 2.50 (ddd, Jgem
indicated 13C nuclei are quaternary and were distinguished in an
16.5 Hz, J6ꢀH(1),5 = 5.4 Hz, J6ꢀH(1),8ꢀH(2) = 2.0 Hz, 1H, 6ꢀH1), 2.79
(mc, 1H, 5ꢀH), 3.07 (dd, Jgem = 16.4 Hz, J6ꢀH(2),5 = 12.0 Hz, 1H, 6ꢀ
H2), 3.52 (dd, J8a,8ꢀH(1) = 5.7 Hz, J8a,8ꢀH(2) = 2.3 Hz, 1H, 8aꢀH),
4
2
3
4
HMBC spectrum by their crosspeaks due to J, J and/or J couꢀ
plings to "remote" protons. edHSQC ["shortꢀrange C,HꢀCOSY
spectrum" (125.8/500.32 MHz), CDCl3] [δC(13C) ↔ δH(1H)]: δC =
21.2 (Cꢀ5''') ↔ δH = 21.20 (5'''ꢀH3); δC = 23.8 (Cꢀ5'''') ↔ δH = 0.83
(5''''ꢀH3); δC = 25.8 (Cꢀ5'') ↔ δH = 1.43 (5''ꢀH); δC = 28.1 (COMe)
↔ δH = 2.13 (COMe); δC = 36.8 (Cꢀ5) ↔ δH = 2.53 (5ꢀH); δC =
36.8 (Cꢀ8) ↔ δH = 1.94 (8ꢀH1); δC = 36.8 (Cꢀ8) ↔ δH = 2.53 (8ꢀ
H2); δC = 39.5 (Cꢀ5') ↔ δH = 1.10 (5'ꢀH1); δC = 39.5 (Cꢀ5') ↔ δH
= 1.56 (5'ꢀH2); δC = 43.6 (Cꢀ6) ↔ δH = 2.53 (6ꢀHA); δC = 43.6 (Cꢀ
6) ↔ δH = 2.74 (6ꢀHB); δC = 45.2 (Cꢀ8a) ↔ δH = 3.22 (8aꢀH); δC
= 64.9 (Cꢀ1'') ↔ δH = 4.01 (1''ꢀHA); δC = 64.9 (Cꢀ1'') ↔ δH = 4.19
(1''ꢀHB); δC = 66.1 (Cꢀ1') ↔ δH = 3.85 (1'ꢀHA); δC = 66.1 (Cꢀ1')
↔ δH = 4.01 (1'ꢀHB); δC = 127.9 (Cꢀ3) ↔ δH = 6.02 (3ꢀH); δC =
144.0 (Cꢀ2) ↔ δH = 6.59 (2ꢀH). HMBC ["longꢀrange C,HꢀCOSY
spectrum" (125.8/500.32 MHz), CDCl3] [δC(13C) ↔ δH(1H)]: δC =
66.0 (Cꢀ4a) ↔ δH = 1.10 (5'ꢀH1), δH = 1.56 (5'ꢀH2), δH = 1.94 (8ꢀ
H1), δH = 2.13 (COMe), δH = 2.53 (8ꢀH2, 6ꢀHA, 5ꢀH), δH = 2.74
(6ꢀHB), δH = 3.22 (8aꢀH), and δH = 6.02 (3ꢀH); δC = 104.3 (Cꢀ1)
↔ δH = 1.94 (8ꢀH1), δH = 2.53 (8ꢀH2, 5ꢀH), δH = 3.22 (8aꢀH), δH =
3.85 (1'ꢀHA), δH = 4.01 (1'ꢀHB, 1''ꢀHA), δH = 4.19 (1''ꢀHB), and δH
= 6.02 (3ꢀH); δC = 198.7 (Cꢀ4) ↔ δH = 2.53 (8ꢀH2, 6ꢀHA, 5ꢀH), δH
= 3.22 (8aꢀH), and δH = 6.59 (2ꢀH); δC = 205.0 (COMe) ↔ δH =
2.13 (COMe), δH = 2.53 (8ꢀH2, 6ꢀHA, 5ꢀH), and δH = 3.22 (8aꢀH);
δC = 207.3 (Cꢀ7) ↔ δH = 1.10 (5'ꢀH1), δH = 1.94 (8ꢀH1), δH = 2.53
(8ꢀH2, 6ꢀHA, 5ꢀH), δH = 2.74 (6ꢀHB), and δH = 3.22 (8aꢀH). DQF-
COSY ["H,HꢀCOSY spectrum" (500.32 MHz), CDCl3] [δH(1H)
↔ δH(1H)]: δH = 0.83 (5''''ꢀH3) ↔ δH = 21.20 (5'''ꢀH3); δH = 1.43
(5''ꢀH) ↔ δH = 21.20 (5'''ꢀH3), 0.83 (5''''ꢀH3), and 1.10 (5'ꢀH1); δH
= 1.56 (5'ꢀH2) ↔ δH = 1.10 (5'ꢀH1); δH = 2.53 (8ꢀH2) ↔ δH = 1.94
(8ꢀH1); δH = 2.53 (5ꢀH) ↔ δH = 1.56 (5'ꢀH2); δH = 2.74 (6ꢀHB) ↔
δH = 2.53 (5ꢀH); δH = 3.22 (8aꢀH) ↔ δH = 1.94 (8ꢀH1) and 2.53
(8ꢀH2); δH = 4.01 (1'ꢀHB, 1''ꢀHA) ↔ δH = 3.85 (1'ꢀHA); δH = 4.19
(1''ꢀHB) ↔ δH = 3.85 (1'ꢀHA) and 4.01 (1'ꢀHB, 1''ꢀHA); δH = 6.59
(2ꢀH) ↔ δH = 6.02 (3ꢀH). IR (Film): υ = 2960, 2920, 2870, 1715,
1670, 1205, 1135, 1015, 975, 915 cmꢀ1. HRMS (pos. APCI) m/z:
[M + H]+ calcd for C18H25O5, 321.1697; found, 321.1695.
3.82ꢀ3.87 (m, 1H, 1'ꢀHA)*, 4.00ꢀ4.05 (m, 2H, 1'ꢀHB, 1''ꢀHA)*,**
,
4.16ꢀ4.20 (m, 1H, 1''ꢀHB)**, 6.21 (d, J3,2 = 10.6 Hz, 1H, 3ꢀH), 6.71
(d, J2,3 = 10.6 Hz, 1H, 2ꢀH), 7.38ꢀ7.42 (m, 2H, 2 × metaꢀH), 7.49ꢀ
7.52 (m, 1H, paraꢀH), 7.66ꢀ7.68 (m, 2H, 2 × orthoꢀH); *,** asꢀ
signment interchangeable. 13C NMR (125.8 MHz, CDCl3): δ =
16.2 (Cꢀ5')A, 35.1 (Cꢀ5)A, 36.5 (Cꢀ8)A, 45.7 (Cꢀ6)A, 46.9 (Cꢀ8a)A,
63.0 (Cꢀ4a)B, 64.9 (Cꢀ1'')*,A, 66.0 (Cꢀ1')*,A, 104.2 (Cꢀ1)B, 127.9
(Cꢀ3)A, 128.7 (2 × Cꢀmeta)A, 129.5 (2 × Cꢀortho)A, 133.0 (Cꢀ
para)A, 134.5 (Cꢀipso)B, 144.6 (Cꢀ2)A, 197.3 (COPh)B, 198.0 (Cꢀ
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
*
A
4)B, 207.6 (Cꢀ7)B; assignment interchangeable; the indicated
13C nuclei – they are nonꢀquaternary – were identified in an
edHSQC spectrum by their crosspeaks with directly bonded proꢀ
tons; the indicated 13C nuclei are quaternary and were distinꢀ
guished in an HMBC spectrum by their crosspeaks due to J, J
and/or J couplings to "remote" protons. edHSQC ["shortꢀrange
B
2
3
4
C,HꢀCOSY spectrum" (125.8/500.32 MHz), CDCl3] [δC(13C) ↔
δH(1H)]: δC = 16.2 (Cꢀ5') ↔ δH = 1.15 (5'ꢀH3); δC = 35.1 (Cꢀ5)
↔ δH = 2.79 (5ꢀH); δC = 36.5 (Cꢀ8) ↔ δH = 1.88 (8ꢀH1); δC = 36.5
(Cꢀ8) ↔ δH = 2.40 (8ꢀH2); δC = 45.7 (Cꢀ6) ↔ δH = 2.50 (6ꢀH1); δC
= 45.7 (Cꢀ6) ↔ δH = 3.07 (6ꢀH2); δC = 46.9 (Cꢀ8a) ↔ δH = 3.52
(8aꢀH); δC = 64.9 (Cꢀ1'') ↔ δH = 4.03 (1''ꢀHA); δC = 64.9 (Cꢀ1'')
↔ δH = 4.18 (1''ꢀHB); δC = 66.0 (Cꢀ1') ↔ δH = 3.84 (1'ꢀHA); δC =
66.0 (Cꢀ1') ↔ δH = 4.03 (1'ꢀHB); δC = 127.9 (Cꢀ3) ↔ δH = 6.21 (3ꢀ
H); δC = 128.7 (Cꢀmeta) ↔ δH = 7.40 (metaꢀH); δC = 129.5 (Cꢀ
ortho) ↔ δH = 7.67 (orthoꢀH); δC = 133.0 (Cꢀpara) ↔ δH = 7.51
(paraꢀH); δC = 144.6 (Cꢀ2) ↔ δH = 6.71 (2ꢀH). HMBC ["longꢀ
range C,HꢀCOSY spectrum" (125.8/500.32 MHz), CDCl3]
[δC(13C) ↔ δH(1H)]: δC = 63.0 (Cꢀ4a) ↔ δH = 1.15 (5'ꢀH3), δH =
1.88 (8ꢀH1), δH = 2.40 (8ꢀH2), δH = 2.50 (6ꢀH1), δH = 2.79 (5ꢀH),
δH = 3.07 (6ꢀH2), δH = 3.52 (8aꢀH), and δH = 6.21 (3ꢀH); δC
=
104.2 (Cꢀ1) ↔ δH = 1.88 (8ꢀH1), δH = 2.40 (8ꢀH2), δH = 3.52 (8aꢀ
H), δH = 3.84 (1'ꢀHA), δH = 4.03 (1'ꢀHB, 1''ꢀHA), δH = 4.18 (1''ꢀHB),
δH = 6.21 (3ꢀH), and δH = 6.71 (2ꢀH); δC = 134.5 (Cꢀipso) ↔ δH =
7.40 (metaꢀH); δC = 197.4 (COPh) ↔ δH = 2.79 (5ꢀH), δH = 3.52
(8aꢀH), δH = 7.40 (metaꢀH), and δH = 7.67 (orthoꢀH); δC = 198.0
(Cꢀ4) ↔ δH = 6.21 (3ꢀH) and δH = 6.71 (2ꢀH); δC = 207.6 (Cꢀ7) ↔
δH = 1.15 (5'ꢀH3), δH = 1.88 (8ꢀH1), δH = 2.40 (8ꢀH2), δH = 2.50
(6ꢀH1), δH = 3.07 (6ꢀH2), and δH = 3.52 (8aꢀH). DQF-COSY
["H,HꢀCOSY spectrum" (500.32 MHz), CDCl3] [δH(1H) ↔
δH(1H)]: δH = 2.40 (8ꢀH2) ↔ δH = 1.88 (8ꢀH1); δH = 2.79 (5ꢀH) ↔
δH = 1.15 (5'ꢀH3) and δH = 2.50 (6ꢀH1); δH = 3.07 (6ꢀH2) ↔ δH =
2.50 (6ꢀH1) and δH = 1.15 (5'ꢀH3); δH = 3.52 (8aꢀH) ↔ δH = 1.88
(4a'S,5'S,8a'S)-4a'-Benzoyl-5'-methyl-5',6',8',8a'-tetrahydro-
4'H-spiro(naphthalene-2,1'-[1,3]dioxolane)-4',7'(4a'H)-dione
(cis,synꢀ7e)
(8ꢀH1) and δH = 2.40 (8ꢀH2); δH = 4.03 (1'ꢀHB, 1''ꢀHA) ↔ δH
=
3.84 (1'ꢀHA); δH = 4.18 (1''ꢀHB) ↔ δH = 3.84 (1'ꢀHA) and δH = 4.03
(1'ꢀHB, 1''ꢀHA); δH = 6.71 (2ꢀH) ↔ δH = 6.21 (3ꢀH); δH = 7.51 (paꢀ
raꢀH) ↔ δH = 7.40 (metaꢀH); δH = 7.67 (orthoꢀH) ↔ δH = 7.40
(metaꢀH). IR (Film): υ = 2985, 2920, 2870, 1715, 1675, 1265,
230, 1020, 970, 915 cmꢀ1. HRMS (pos. APCI) m/z: [M + H]+
calcd for C20H21O5, 341.1384; found, 341.1383.
At 0°C F3CCO2H (1 mL) was added dropwise to a solution of the
Deslongchamps adduct cis,synꢀ6e (45.4 mg, 0.10 mmol,
1.0 equiv.) in CH2Cl2 (4 mL) within 5 min. The mixture was
stirred at 0°C for 2 h. The solvent was removed and F3CCO2H
was removed azeotropically with C6H6 (3 × 4 mL) under reduced
pressure. The remaining solid was dissolved in C6H6 (4 mL) and
stirred at room temp. for 8 d. The solvent was evaporated and the
residue was purified by flash chromatography on silica gel36
[2 cm × 15 cm, cC6H12:EtOAc 8:1 to 1:1 (v:v), 20 mL] to render
the title compound (F34ꢀ45; 26.1 mg, 76%) as colorless solid.
(4a'S,5'S,8a'S)-4a'-benzoyl-5'-isobutyl-5',6',8',8a'-tetrahydro-
4'H-spiro(naphthalene-2,1'-[1,3]dioxolane)-4',7'(4a'H)-dione
(cis,synꢀ7f)
1
Melting point: 115ꢀ120°C. H NMR (500.32 MHz, CDCl3): δ =
17
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 18 of 21
para
5''''
COSY ["H,HꢀCOSY spectrum" (500.32 MHz), CDCl3] [δH(1H)
ipso
O
O
meta
↔ δH(1H)]: δH = 1.47 (5''ꢀH) ↔ δH = 0.71 (5'''ꢀH3), δH = 0.87 (5''''ꢀ
5''
4a'
1
2
3
4
5
6
7
8
ortho
O
O
5'
5'''
5'
5
numbering for UPAC
nomenclature
numbering for NMR
assignment
6
7
6'
7'
3
2
3'
2'
4'
2
4
1
H3), and δH = 1.33 (5'ꢀH1); δH = 1.74 (5'ꢀH2) ↔ δH = 1.33 (5'ꢀH1);
δH = 2.38 (8ꢀH2) ↔ δH = 1.84 (8ꢀH1); δH = 2.66 (5ꢀH, 6ꢀHA) ↔ δH
= 1.74 (5'ꢀH2); δH = 2.91 (6ꢀHB) ↔ δH = 2.66 (5ꢀH, 6ꢀHA); δH =
3.53 (8aꢀH) ↔ δH = 1.84 (8ꢀH1) and δH = 2.38 (8ꢀH2); δH = 4.03
4a'
8a'
4a
8a
O
O
8'
8
O
O
O
O
5
1'
4
1''
(1'ꢀHB, 1''ꢀHA) ↔ δH = 3.84 (1'ꢀHA); δH = 4.18 (1''ꢀHB) ↔ δH
=
At 0°C F3CCO2H (1 mL) was added dropwise to a solution of the
Deslongchamps adduct cis,synꢀ6f (49.7 mg, 0.10 mmol,
1.0 equiv.) in CH2Cl2 (4 mL) within 5 min. The mixture was
stirred at 0°C for 2 h. The solvent was removed and F3CCO2H
was removed azeotropically with C6H6 (3 × 4 mL) under reduced
pressure. The remaining solid was dissolved in C6H6 (4 mL) and
stirred at room temp. for 8 d. The solvent was evaporated and the
residue was purified by flash chlromatography on silica gel36
[2 cm × 15 cm, cC6H12:EtOAc 8:1 to 1:1 (v:v), 20 mL] to render
the title compound (F26ꢀ38; 11.4 mg, 29%) as pale orange oil.
1H NMR (500.32 MHz, CDCl3): δ = 0.71 (d, J5''',5'' = 6.5 Hz, 3H,
3.84 (1'ꢀHA) and δH = 4.03 (1'ꢀHB, 1''ꢀHA); δH = 7.51 (2ꢀH) ↔ δH
= 6.19 (3ꢀH); δH = 7.51 (paraꢀH) ↔ δH = 7.40 (metaꢀH); δH = 7.66
(orthoꢀH) ↔ δH = 7.40 (metaꢀH). IR (Film): υ = 3180, 2990,
2930, 2870, 1715, 1700, 1675, 1235, 1140, 1100, 985, 975, 935,
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
915, cmꢀ1. HRMS (pos. ESI) m/z: [M
+
Na]+ calcd for
C23H26O5Na, 405.1673; found, 405.1672.
Monitoring Deslongchamps Annulations:
The indicated quinone monoketal 5b, c or d (1.0 equiv.), a Nazaꢀ
rov reagent 2a or b (1.05 equiv.), and the internal standard 2,4,6ꢀ
tribromotoluene (0.5 equiv.) were dissolved in CH2Cl2 (c =
0.06 mol/L) at room temperature (scale of these experiments: Secꢀ
tion SI-4 of the Supporting Information). The reaction was started
(t = 0) by the addition of Cs2CO3 (1.0 equiv.) in one portion. Aliꢀ
quots of the reaction mixture (0.4 mL) were sampled after 1, 2, 3,
4, 6, 8, 10, 20, 40, and 80 min (when monitoring the formation of
cis,synꢀ6f, we also sampled after 160 and 320 min). Each sample
was loaded onto a small glass column filled with silica gel (∅ =
5 mm, h = 2 cm) and eluted with AcOEt (3 mL). The eluate was
5'''ꢀH3), 0.87 (d, J5'''',5'' = 6.6 Hz, 3H, 5''''ꢀH3), 1.33 (ddd, Jgem
=
14.3 Hz, J5'ꢀH(1),5 = 9.8 Hz, J5'ꢀH(1),5'' = 2.2 Hz, 1H, 5'ꢀH1), 1.43ꢀ1.50
(m, 1H, 5''ꢀH), 1.70ꢀ1.77 (m, 1H, 5'ꢀH2), 1.84 (dd, Jgem = 16.4 Hz,
J8ꢀH(1),8a = 5.7 Hz, 1H, 8ꢀH1), 2.38 (ddd, Jgem = 16.4 Hz, J8ꢀH(2),8a
=
2.2 Hz, J8ꢀH(2),6ꢀH(A) = 2.2 Hz, 1H, 8ꢀH2), 2.62ꢀ2.69 (m, 2H, 5ꢀH,
6ꢀHA), 2.87ꢀ2.94 (m, 1H, 6ꢀHB), 3.53 (dd, J8a,8ꢀH(1) = 5.6 Hz, J8a,8ꢀ
H(2) = 2.3 Hz, 1H, 8aꢀH), 3.81ꢀ3.87 (m, 1H, 1'ꢀHA)*, 4.00ꢀ4.06 (m,
4
2H, 1'ꢀHB, 1''ꢀHA)*,**, 4.16ꢀ4.20 (m, 1H, 1''ꢀHB)**, 6.19 (d, J3,2
=
10.3 Hz, 1H, 3ꢀH), 6.71 (d, J2,3 = 10.3 Hz, 1H, 2ꢀH), 7.38ꢀ7.42
(m, 2H, metaꢀH), 7.94ꢀ7.53 (m, 1ꢀH, paraꢀH), 7.65ꢀ7.68 (m, 2H,
orthoꢀH); *,** assignment interchangeable. 13C NMR (125.8 MHz,
CDCl3): δ = 21.4 (Cꢀ5''')A, 23.7 (Cꢀ5'''')A, 26.3 (Cꢀ5'')A, 36.5 (Cꢀ
8)A, 38.2 (Cꢀ5)A, 39.7 (Cꢀ5')A, 44.0 (Cꢀ6)A, 47.1 (Cꢀ8a)A, 64.0 (Cꢀ
4a)B, 64.9 (Cꢀ1'')*,A, 66.0 (Cꢀ1')*,A, 104.2 (Cꢀ1)B, 127.9 (Cꢀ3)A,
128.7 (2 × Cꢀmata)A, 129.6 (2 × Cꢀortho)A, 133.0 (Cꢀpara)A, 134.5
(Cꢀipso)B, 144.5 (Cꢀ2)A, 197.7 (COPh)B, 198.3 (Cꢀ4)B, 207.5 (Cꢀ
7)B;* assignment interchangeable; A the indicated 13C nuclei – they
are nonꢀquaternary – were identified in an edHSQC spectrum by
1
collected, the solvent evaporated, and the residue analyzed Hꢀ
NMR spectroscopically at 300 MHz. The respective results for
each monitoring reaction are detailed in Section SI-4 of the Supꢀ
porting Information).
Performing Deslongchamps Annulations as Cross-over Exper-
iments:
their crosspeaks with directly bonded protons; the indicated 13C
B
The quinone monoketal/ Nazarov reagent pairs 5b/2a and 5c/2b
(0.42 mmol of each of the reactants) were dissolved in CH2Cl2 (c
= 0.05 mol/L each) at room temperature in two separate flasks.
The reactions were started simultaneously by addition of Cs2CO3
(0.42 mmol, 1.0 equiv. each). After two minutes the contents of
the two flasks were mixed. Stirring was continued for another 2 h.
The reaction was stopped by filtration over silica gel (∅ = 2 cm, h
= 1 cm) and eluted with EtOAc (50 mL). The solvent was evapoꢀ
nuclei are quaternary and were distinguished in an HMBC specꢀ
2
3
4
trum by their crosspeaks due to J, J and/or J couplings to "reꢀ
mote" protons. edHSQC ["shortꢀrange C,HꢀCOSY spectrum"
(125.8/500.32 MHz), CDCl3] [δC(13C) ↔ δH(1H)]: δC = 21.4 (Cꢀ
5''') ↔ δH = 0.71 (5'''ꢀH3); δC = 23.7 (Cꢀ5'''') ↔ δH = 0.87 (5''''ꢀH3);
δC = 26.3 (Cꢀ5'') ↔ δH = 1.47 (5''ꢀH); δC = 36.5 (Cꢀ8) ↔ δH = 1.84
(8ꢀH1); δC = 36.5 (Cꢀ8) ↔ δH = 2.38 (8ꢀH2); δC = 38.2 (Cꢀ5) ↔ δH
= 2.66 (5ꢀH); δC = 39.7 (Cꢀ5') ↔ δH = 1.33 (5'ꢀH1); δC = 39.7 (Cꢀ
5') ↔ δH = 1.74 (5'ꢀH2); δC = 44.0 (Cꢀ6) ↔ δH = 2.66 (6ꢀHA); δC =
44.0 (Cꢀ6) ↔ δH = 2.91 (6ꢀHB); δC = 47.1 (Cꢀ8a) ↔ δH = 3.53
(8aꢀH); δC = 64.9 (Cꢀ1'') ↔ δH = 4.03 (1''ꢀHA); δC = 64.9 (Cꢀ1'')
↔ δH = 4.18 (1''ꢀHB); δC = 66.0 (Cꢀ1') ↔ δH = 3.84 (1'ꢀHA); δC =
66.0 (Cꢀ1') ↔ δH = 4.03 (1'ꢀHB); δC = 127.9 (Cꢀ3) ↔ δH = 6.19 (3ꢀ
H); δC = 128.7 (Cꢀmata) ↔ δH = 7.40 (metaꢀH); δC = 129.6 (Cꢀ
ortho) ↔ δH = 7.66 (orthoꢀH); δC = 133.0 (Cꢀpara) ↔ δH = 7.51
(paraꢀH); δC = 144.5 (Cꢀ2) ↔ δH = 7.51 (2ꢀH). HMBC ["longꢀ
range C,HꢀCOSY spectrum" (125.8/500.32 MHz), CDCl3]
[δC(13C) ↔ δH(1H)]: δC = 64.0 (Cꢀ4a) ↔ δH = 1.33 (5'ꢀH1), δH =
1
rated. The H NMR spectrum (500 MHz, CDCl3) of the crude
product mixture was compared to the spectra of the individual
products prepared independently (cf. Scheme 5). More details: see
Supporting Information SI-5.
Cross-over Experiment of Scheme 6. The setup for this experiꢀ
ment was like in the crossꢀover experiment described above
(Scheme 5). The Enone/Nazarov reagent pairs 5b/2b and 5c/2a
(0.42 mmol, 1.0 equiv. for both pairs of enone and Nazarov reaꢀ
gent) were dissolved in CH2Cl2 (c = 0.05 mol/L each) at room
temperature in two separate flasks. The reactions were started
with a delay of 1 min by addition of Cs2CO3 (0.42 mmol,
1.0 equiv. each). After 2 min (1 min for 5b + 2b) the contents of
the two flasks were mixed together in one flask and the resulting
mixture was stirred for another 2 h. The reaction was stopped by
filtration over silica gel (∅ = 2 cm, h = 1 cm) and eluted with
EtOAc (50 mL). The solvent was evaporated. The 1H NMR specꢀ
trum (500 MHz, CDCl3) of the crude product mixture was comꢀ
pared to the spectra of the individual products prepared indeꢀ
pendently (cf. Scheme 6).
2.38 (8ꢀH2), δH = 2.66 (5ꢀH, 6ꢀHA), δH = 3.53 (8aꢀH), and δH
=
6.19 (3ꢀH); δC = 104.2 (Cꢀ1) ↔ δH = 1.84 (8ꢀH1), δH = 3.53 (8aꢀ
H), δH = 4.03 (1'ꢀHB, 1''ꢀHA), δH = 4.18 (1''ꢀHB), and δH = 6.19 (3ꢀ
H); δC = 134.5 (Cꢀipso) ↔ δH = 7.40 (metaꢀH); δC = 197.7
(COPh) ↔ δH = 7.66 (orthoꢀH); δC = 198.3 (Cꢀ4) ↔ δH = 2.66 (5ꢀ
H, 6ꢀHA), δH = 2.91 (6ꢀHB), δH = 3.53 (8aꢀH), and δH = 7.51 (2ꢀ
H); δC = 207.5 (Cꢀ7) ↔ δH = 1.84 (8ꢀH1), δH = 2.38 (8ꢀH2), δH =
2.66 (5ꢀH, 6ꢀHA), δH = 2.91 (6ꢀHB), and δH = 3.53 (8aꢀH). DQF-
18
ACS Paragon Plus Environment

Page 19 of 21
The Journal of Organic Chemistry
Reversibility Experiments:
The Deslongchamps adduct pair cis,synꢀ6a/6d (211 ꢁmol per
1
2
component) was dissolved in CH2Cl2 (8.4 mL) at room temperaꢀ
ture. The reaction was started by adding solid Cs2CO3 (138 mg,
422 ꢁmol, 2.0 equiv.). The mixture was stirred for 6 h. After 1, 2,
3, and 6 h aliquots of 0.4 mL were sampled, Each specimen was
filtered through a syringe filter (0.2 ꢁm pore) and eluted with
3
4
5
6
7
8
9
(1) The value of Deslongchamps annulations for synthesizing polyꢀ
cyclic natural products was highlighted in the following articles: (a)
Audran, G.; Brémond, P.; Feuerstein, M.; Marque, S. R. A.; Santelli,
M. Tetrahedron 2013, 69, 8325ꢀ8348 (section 6 therein). (b) Heasley,
B. Chem. Eur. J. 2012, 18, 3092ꢀ3120.− c) For an overview of the
scope of Deslongchamps annulations see the references cited in ref.21.
(2) Nazarov, I. N.; Zauyalou, S. I. Zh. Obshch. Khim. 1953, 23,
1703ꢀ1706 (Chem. Abs. 1954, 48, 77597).
1
EtOAc (3 mL). The filtrate was evaporated. The HꢀNMR specꢀ
trum (500 MHz, CDCl3) of the respective residue was identical
with the spectrum of the unaltered adduct pair cis,synꢀ6a/6d, that
is, no reaction had occurred.
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
(3) Lavallée, J.ꢀF.; Deslongchamps, P. Tetrahedron Lett. 1988, 29,
An analogous experiment was performed starting with another
pair of Deslongchamps adducts: cis,synꢀ6b and cis,synꢀ6c. The
execution and the result of this experiment were identical to the
one described above
5117ꢀ5118 (full paper: ref.7).
(4) Lavallée, J.ꢀF.; Deslongchamps, P. Tetrahedron Lett. 1988, 29,
6033ꢀ6036.
(5) Ruel, R.; Deslongchamps, P. Tetrahedron Lett. 1990, 31, 3961ꢀ
3964.
(6) Ruel, R.; Hogan, K. T.; Deslongchamps, P. Synlett 1990, 516ꢀ
Performing Deslongchamps Annulations as Scavenging Ex-
periments:
518 (full paper: ref.7).
(7) Lavallée, J.ꢀF.; Spino, C.; Ruel, R.; Hogan, K. T.; Deslongꢀ
champs, P. Can. J. Chem. 1992, 70, 1406ꢀ1426.
(8) Ruel, R.; Deslongchamps, P. Can. J. Chem. 1992, 70, 1939ꢀ
1949.
(9) Chapdelaine, D.; Belzile, J.; Deslongchamps, P. J. Org. Chem.
2002, 67, 5669ꢀ5672.
(10) Lepage, O.; Stone, C.; Deslongchamps, P. Org. Lett. 2002, 4,
1091ꢀ1094.
(11) Yang, Z.; Shannon, D.; Truong, V.ꢀL.; Deslongchamps, P.
Org. Lett. 2002, 4, 4693ꢀ4696.
(12) Lepage, O.; Deslongchamps, P. J. Org. Chem. 2003, 68, 2183ꢀ
2186.
(13) Guay, B.; Deslongchamps, P. J. Org. Chem. 2003, 68, 6140ꢀ
6148.
(14) Rouillard, A.; Bonin, M.ꢀA.; Deslongchamps, P. Helv. Chim.
Acta 2003, 86, 3730ꢀ3739.
(15) Trudeau, S.; Deslongchamps, P. J. Org. Chem. 2004, 69, 832ꢀ
838.
(16) Chen, L.; Deslongchamps, P. Can. J. Chem. 2005, 83, 728ꢀ
740.
(17) Tricotet, T.; Brückner, R. Eur. J. Org. Chem. 2007, 1069ꢀ
1074.
(18) Zhang, H.; Reddy, M. S.; Phoenix, S.; Deslongchamps, P. Anꢀ
gew. Chem. 2008, 120, 1292ꢀ1295; Angew. Chem. Int. Ed. 2008, 47,
1272ꢀ1275.
(19) Caron, P.ꢀY.; Deslongchamps, P. Org. Lett. 2010, 12, 508ꢀ
511.
(20) (a) Ravindar, K.; Caron, P.ꢀY.; Deslongchamps, P. Org. Lett.
2013, 15, 6270ꢀ6273. (b) Ravindar, K.; Caron, P.ꢀY.; Deslongchamps,
P. J. Org. Chem. 2014, 79, 7979ꢀ7999.
(21) Petrović, D.; Brückner, R. Org. Lett. 2011, 13, 6524ꢀ6527.
(22) Interestingly, the substitution patterns of annulates 6 and 7 are
inaccessible by “genuine” DielsꢀAlder reactions of benzoquinone
monoketals. Examples are listed in Section SI-9 of the Supporting Inꢀ
formations.
(23) Petrović, D. Ph. D. Thesis, Freiburg, 2012.
(24) (a) What we call “sequential Michael additions” would be
“domino Michael additions“ according to the nomenclature suggested
by Tietze:25a “A domino reaction is a process involving two or more
bondꢀforming transformations (usually CꢀC bonds) which take place
under the same reaction conditions without adding additional reagents
and catalysts, and in which the subsequent reactions result as a conseꢀ
quence of the functionality formed in the previous step.” (b) "Cascade
Michael additions”, ”tandem Michael additions”, or “consecutive Miꢀ
chael additions” might be terms preferred by others when referring to
the identical course of events.25
Each of the enone / “first Nazarov reagent” pairs 5b/2a, 5b/2b,
5c/2a, and 5c/2b (228 ꢁmol per compound) and 2,4,6ꢀ
tribromotoluene (37.5 mg, 114 ꢁmol, 0.5 equiv.) was dissolved in
CH2Cl2 (4.2 mL) separately at room temperature. The respective
reactions were started by addition of Cs2CO3 (74.3 mg, 288 ꢁmol,
1.0 equiv.). After 2 min (1 min for 5b/2b; more details: see main
body of the text), the “second Nazarov reagent” (228 ꢁmol,
1.0 equiv.) was added (2b for reactions begun with 2a as the “first
Nazarov reagent”; 2a for reactions begun with 2b as the “first
Nazarov reagent”).
The resulting mixtures were stirred for 6 h. After 1, 2, 3, and 6 h
aliquots of 0.4 mL were sampled, filtered through a syringe filter
(0.2 ꢁm pore width), and eluted with EtOAc (3 mL). The solvent
was evaporated. The 1HꢀNMR spectrum (500 MHz, CDCl3) of the
respective residue was compared to the spectra of the indeꢀ
pendently prepared reference products (see Scheme 7, Scheme 8).
More details: Supporting Information SI-6.
ꢀ ASSOCIATED CONTENT
Supporting Information: Detailed procedures for the synthesis of
Nazarov reagents 2aꢀb and quinone monoketals 5bꢀd, concentraꢀ
tion/time diagrams for the discontinuous NMR monitorings of the
formation of Deslongchamps adducts cis,synꢀ6bꢀf, details of the
crossꢀover and scavenging experiments, copies of NMR spectra,
and Xꢀray details of Deslongchamps adducts 6a, 6c, and 6e. This
material is available free of charge via the Internet at
http://pubs.acs.org.
ꢀ AUTHOR INFORMATION
Corresponding Author
* reinhard.brueckner@organik.chemie.uniꢀfreiburg.de
ꢀ ACKNOWLEDGMENT
We express our gratitude to Dr. Valeska Kreibich for the Xꢀray
analyses and thank Boumahdi Benkmil (Institut für Anorganische
Chemie, AlbertꢀLudwigsꢀUniversität Freiburg) for recording the
diffraction data. Technical assistance by Andreas Miller is greatꢀ
fully acknowledged.
ꢀ REFERENCES
19
ACS Paragon Plus Environment

The Journal of Organic Chemistry
Page 20 of 21
1
2
3
4
(25) Reviews: (a) Tietze, L. F.; Beifuss, U. Angew. Chem. 1993,
from the Cambridge Crystallographic Data Centre via the link
5
6
7
8
105, 137ꢀ170; Angew. Chem., Int. Ed. Engl. 1993, 32, 131ꢀ163. (b)
Bunce, R. A. Tetrahedron 1995, 51, 13103ꢀ13159. (c) Tietze, L. F.
Chem. Rev. 1996, 96, 115ꢀ136. (d) Nicolaou, K. C.; Montagnon, T.;
Snyder, S. A. Chem. Commun. 2003, 551ꢀ564. (e) Tietze, L. F.;
Brasche, G.; Gericke, K. M. "Domino reactions in organic synthesis",
WileyꢀVCH, Weinheim, 2006.− (f) Zhou, J. Chem. Asian J. 2010, 5,
422ꢀ434. (g) Pellissier, H. Chem. Rev. 2013, 113, 442ꢀ524.
(26) Refs.3,6,7 discuss both possibilities. Ref.4 speaks of a Dielsꢀ
Alder addition. Refs.9,10,11,13,18,19 speak of a sequential Michael reacꢀ
tion. Refs.5,8,12,14,15,17,21 remain equivocal. Formally, ref.16 remains
noncomꢀmittal yet interprets the occurrence of a monoꢀMichael adꢀ
duct as strongly suggestive of a double Michael addition pathway for
the overall transformation. For further details about the observation
and/or isolation of the monoꢀMichael adduct, see ref.32.
www.ccdc.cam.ac.uk/data_request/cif.
(38) The crystallographic data of Deslongchamps adduct 6c are
contained in CCDC 1557445. They can be obtained free of charge
from the Cambridge Crystallographic Data Centre via the link
www.ccdc.cam.ac.uk/data_request/cif.
(39) The crystallographic data of Deslongchamps adduct 6e are
contained in CCDC 1557447. They can be obtained free of charge
from the Cambridge Crystallographic Data Centre via the link
www.ccdc.cam.ac.uk/data_request/cif.
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
(40) We could not monitor these reactions in the spectrometer – in
CD2Cl2 solutions – because Cs2CO3 is insoluble therein, forming susꢀ
pensions.
(41) The closeꢀups of Figure 2, the 2nd, and the 4thꢀ6th concentraꢀ
tion/time diagram in Section SI-4 of the Supporting Information illusꢀ
trate that at times our reaction mixture contained less Nazarov reagent
2 than benzoquinonemonoketal 5. This was in spite of using 5 molꢀ%
more 2 than 5. A depletion of 2 relative to 5 nonetheless might be due
to 2 dimerizing or to 2 escaping our sampling procedure by precipitatꢀ
ing as the cesium salt Csꢀ2 (formula: Scheme 3).
(27) Occam's razor prefers a simple explanation (e. g., one mechaꢀ
nism) over a complicated one (e. g., two mechanisms) − unless there
is a necessity for the contrary.
(28) Reichardt, C. Chem. Rev. 1994, 94, 2319ꢀ2358.
(29) Reviews on the stereoselectivity of Michael additions: (a)
Heravi, M. M.; Hajiabbasi, P.; Hamidi, H. Curr. Org. Chem. 2014,
18, 489ꢀ511. (b) Feringa, B. L.; Jansen, J. F. G. A. "Addition of Enoꢀ
lates and Azaenolates to α,βꢀUnsaturated Carbonyl Compounds", in
HoubenꢀWeyl Methods of Organic Chemistry, Supplementary Volume
to the 4th Edition, Vol. E 21b ("Stereoselective Synthesis: CꢀC Bond
Formation by Addition to C=O, C=N and Reactions Involving Olefin
Double Bonds"), Thieme, Stuttgart, 1995, pp. 2104ꢀ2155. (c) Oare, D.
A.; Heathcock, C. H. Top. Stereochem. 1989, 19, 227ꢀ407.
(30) Synꢀselective DielsꢀAlder reactions of 1,3ꢀdienes and alkyl cyꢀ
cloalkꢀ2ꢀenꢀ1ꢀoneꢀ2ꢀcarboxylates are exemplified in Section SI-9 of
the Supporting Informations.
(42) It was not selfꢀevident that we would be able to monitor Deꢀ
slongchamps adducts in the presence of the suspected Michael adduct
intermediates (plural voice; cf. footnote44) by the 1HꢀNMR resonances
of the sp2ꢀbound protons in their cyclohexenone moiety. Chances
were that signal overlap interfered. The factual evidence to the contraꢀ
ry means that the Michael adduct intermediates contained no cycloꢀ
hexenones because tautomerism gave cyclohexadienols (cf. e, f, i, and
j in Figure 3).
(43) The significant delay between reactant consumption and Deꢀ
slongchamps adduct formation means that a fast initial reaction preꢀ
ceded product formation. Unfortunately, 1H NMR signal overlap
made a direct determination of the concentration of the intermediꢀ
ate(s) and/or sideꢀproduct(s) impossible. To which extent intermediꢀ
ates and/or sideꢀproducts accumulated in the course of our annulaꢀ
tions, was an estimate, accordingly. We equalled their total amount to
the difference between the initial amount of the starting material and
the sum of the amounts of residual starting material and already
formed Deslongchamps product.
(44) The singular form ”the Michael adduct” for the intermediates
13ꢀ18 (Figure 3) should not be understood literally. This is because
the triꢀketo tautomer of each such compound contains three stereocenꢀ
ters and might therefore comprise four diastereomers aꢀd. Moreover,
the acyclic βꢀketoester moiety of the Michael adduct may be enolized
(ꢀe, f). The same is conceivable for the cyclohexenone moiety (ꢀg,
h) and, in addition, concomitantly in the acyclic in βꢀketoester and in
the cyclohexenone moiety (ꢀi, j; see also footnote 42). Two enols of
a given constitution − i. e., the kinds of isomers mentioned last − may
arise as pairs of (E)ꢀ and (Z)ꢀisomers. Furthermore, each component
therein might represent a diastereomeric mixture because it contains
two stereocenters.
(45) We used a total excess of 1.00 equiv. of Nazarov reagent in
each of the four scavenging experiments of Scheme 7 and Scheme 8.
After the respective mixture had reacted fore 3 h, we found no Nazaꢀ
rov reagent in any reaction mixture (500 MHz 1H NMR). A “sink” for
excess Nazarov reagents might precipitating as the cesium salt Csꢀ2
(formula: Scheme 3). Since we filtered the crude product without exꢀ
posing it to water, such a precipate might have evaded our analyses.
(46) An intramolecular 6ꢀring formation between a dienolate and
an enoate – preceding a followꢀup reaction leading to an 6ꢀring free
isomer – was calculated to proceed via a Michael/Michael tandem adꢀ
dition rather than by an anionic DielsꢀAlder reaction by Kiss, E.;
Campbell, C. D.; Driver, R. W.; Jolliffe, J. D.; Lang, R.; Sergeieva,
(31) Examples for antiꢀselective DielsꢀAlder reactions of 1,3ꢀ
dienes and alkyl cyclohexꢀ2ꢀenꢀ1ꢀoneꢀ2ꢀcarboxylates are exemplified
in Section SI-9 of the Supporting Informations.
(32) The same acceptorꢀsubstituted cyclohexenone 1 (EWG =
CO2Me, Rx = H; Scheme 1) and another and sterically more hindered
Nazarov reagent than the one mentioned so far combined to form a
Michael adduct at −15°C in acetonitrile as well.6,7 However, it gave
no Deslongchamps annulation product under any circumstances,
which was described as if it corroborated sequential Michael additions
occurring in the course of Deslongchamps annulations, which, in conꢀ
trast, work.16 However, the nonꢀfeasibility of a Deslongchamps annuꢀ
lation with the “sterically more hindered Nazarov reagent” mentioned
above implies nothing certain about the mechanism of a Deslongꢀ
champs annulation, which is actually feasible.
(33) DFT calculations regarding the alternative mechanisms were
undertaken in our laboratory, too, employing various functionals
(Weber, F. Dissertation, Universität Freiburg 2015). They revealed
that an “anionic” DielsꢀAlder reaction is impossible and that the first
Michael addition is irreversible. The first result may be true or not,
whereas the second result disagrees with the experiments reported in
this manuscript.
(34) (a) First mentioning in the literature: ref.3. (b) First description
of a respective synthesis: ref.7. (c) New synthesis of Nazarov reagent
2a: Experimental section and Section SI-1 of the Supporting Inforꢀ
mations.
(35) (a) First mentioning in the literature: ref.21. (b) New synthesis
of Nazarov reagent 2b: Experimental section.
(36) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43,
2923ꢀ2925.
(37) The crystallographic data of Deslongchamps adduct 6a are
contained in CCDC 1557446. They can be obtained free of charge
20
ACS Paragon Plus Environment

Page 21 of 21
The Journal of Organic Chemistry
1
2
3
4
T.; Okovytyy, S.; Paton, R. S.; Smith, M. D. Angew. Chem. 2016,
5
6
7
128, 14017ꢀ14021; Angew. Chem. Int. Ed. 2016, 55, 13813ꢀ13817.
(47) The latter compound was obtained as described in the Supꢀ
porting Information.
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
21
ACS Paragon Plus Environment