Directed ortho -Metalation and Anionic ortho -Fries Rearrangement of Polycyclic Aromatic O -Carbamates: Regioselective Synthesis of Substituted Chrysenes

Article abstract of DOI:10.1021/acs.joc.7b03210

A general method for the regioselective synthesis of a series of ortho-substituted chrysenyl N,N-diethyl-O-carbamates by the directed ortho-metalation (DoM) strategy is reported. The starting O-carbamates were prepared from the corresponding chrysenols, available by oxidative photochemical cyclization or directed remote metalation tactics. Chrysen-1-yl and chrysene-3-yl ring site selectivity of directed ortho-metalation (DoM) and anionic ortho-Fries rearrangement (AoF) protocols, with s-BuLi/TMEDA, followed by electrophilic quench using a selection of electrophiles, were observed, leading to new chrysenyl derivatives. 5-Chrysenyl N,N-diethyl-O-carbamate underwent instant AoF rearrangement even at -100 °C to furnish chrysenyl o-hydroxycarboxamide. Iterative DoM reactions were carried out to gain insight into the regioselectivity factors.

Full text of DOI:10.1021/acs.joc.7b03210

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Directed ortho Metalation and Anionic ortho Fries
Rearrangement of Polycyclic Aromatic O-Carbamates:
Regioselective Synthesis of Substituted Chrysenes
Sindhu Kancherla, Marianne Lorentzen, Victor Snieckus, and Kåre Bredeli Jørgensen
J. Org. Chem., Just Accepted Manuscript • Publication Date (Web): 15 Mar 2018
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Directed ortho Metalation and Anionic ortho Fries Rearrangement of
Polycyclic Aromatic O-Carbamates: Regioselective Synthesis of
Substituted Chrysenes
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*
Sindhu Kancherla†, Marianne Lorentzen†, Victor Snieckus‡, Kåre B. Jørgensen†
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† Faculty of Science and Technology, University of Stavanger, Nꢀ4036 Stavanger, Norway; ‡ Department of
Chemistry, Queen’s University, 90 Bader Lane, Kingston, ON K7L 3N6, Canada
KEYWORDS: Directed ortho Metalation (DoM), polycyclic aromatic hydrocarbons, chrysenes, anionic
ortho Fries rearrangement (AoF)
ABSTRACT
A general method for the regioselective synthesis of a series of orthoꢀsubstituted chrysenyl N,NꢀdiethylꢀOꢀ
carbamates by the directed ortho metalation (DoM) strategy is reported. The starting Oꢀcarbamates were
prepared from corresponding chrysenols, available by oxidative photochemical cyclization or directed
remote metalation tactics. Chrysenꢀ1ꢀyl and chryseneꢀ3ꢀyl ring site selectivity of directed ortho metalation
(DoM) and anionic ortho Fries rearrangement (AoF) protocols, with sꢀBuLi/TMEDA, followed by
electrophilic quench using a selection of electrophiles, were observed leading to new chrysenyl
derivatives. 5ꢀChrysenyl N,NꢀdiethylꢀOꢀcarbamate underwent instant AoF rearrangement even at ꢀ100 °C
to furnish chrysenyl orthoꢀhydroxycarboxamide. Iterative DoM reactions were carried out to gain insight in
the regioselectivity factors.
INTRODUCTION
Polycyclic aromatic hydrocarbons (PAHs) are wellꢀknown carcinogenic and mutagenic pollutants in the
environment1,2 whose synthesis is of longstanding interest for the provision of analytical standards.3,4
Currently, PAHs are also gaining substantial attention among material science and medicinal chemists.
Thus, the synthesis of extended and helical polycyclic aromatic structures is of major interest due to their
application in organic fieldꢀeffect transistors (OFETs), photovoltaics, lightꢀemitting diodes,5,6 and
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superconductors.7, 8 The particular chrysene class of PAHs possess photophysical properties which have
found utility as fluorescent OLEDs.9 In the medicinal area, substituted chrysenes have been found to
possess anticancer activity due to their intercalation with DNA10 and have been shown to inhibit the
functioning of topoisomerase II, a potentially advantageous property for cancer chemotherapy.11
9
Traditional synthetic approaches to PAHs involve a multitude of Lewis and Brønsted acid catalyzed SEAr
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reactions,12,
in which the FriedelꢀCraft acylation plays a major role.14 Recently, new methodologies
based on cooperative catalysis,15 radical substitution,16 and, significantly, transition metal catalyzed CꢀH
activation,17 have been developed. The directed ortho metalation (DoM) reaction has contributed new
methodology for the construction of aromatic and heteroaromatic molecules,18ꢀ20 in particular
phenanthrenes.21ꢀ23 Except for minor forays into small polyaromatic systems such as pyreneꢀ1ꢀ
carboxaldehyde,24 2ꢀnaphthylꢀOꢀcarbamates25 and pyreneꢀ1ꢀcarboxamide,26 the DoM strategy has not
been studied in relation to larger PAHs. The fundamental regioselectivity consequences of the DoM
reaction for competitive sites has been studied in two or more DMG benzene derivatives.27
With the aim to contribute new synthetic methodology to this area, we report herein a DoM study on 1ꢀ, 2ꢀ,
3ꢀ and 5ꢀchrysenyl N,N-diethylꢀOꢀcarbamates 2a, 2b, 2c, and 2e. The N,NꢀdiethylꢀOꢀcarbamates were
chosen in view of their very strong DMG power18,19,27 and their recently introduced ability to undergo
SuzukiꢀMiyaura
cross
coupling,28,29
Schwarz
reduction
to
phenols30
and
reductive
hydrodecarbamoylation.31 Thus we view that DoM reactions on larger polyaromatic skeletons offer
considerable potential to further elaborate other and larger PAH skeletons of interest in material science
areas.
RESULTS AND DISCUSSION
To initiate the study, we used the photochemical oxidative cyclization of stilbenes to chrysenes32ꢀ35 which
has proven to be a reliable workhorse in the preparation of methoxychrysenes. The thus prepared
methoxychrysenes, upon deprotection with BBr3 furnished 1ꢀ and 3ꢀ chrysenols 1a (96%) and 1c (98%) in
good to excellent yields (Scheme 1)34 which, upon deprotonation with NaH and trapping with N,Nꢀdiethyl
carbamoyl chloride afforded the Oꢀcarbamoyl chrysenes 2a and 2c in 95% and 91% yield, respectively
(Scheme 1a). 2ꢀMethoxychrysene, separated from 4ꢀmethoxychrysene by recrystallization from acetone,
gave upon deprotection with BBr3, a comparatively less soluble and unstable crude chrysenol 1b which
was immediately subjected to treatment with NaH and N,Nꢀdiethyl carbamoyl chloride to furnish the Oꢀ
carbamoyl chrysene 2b in 85% overall yield. Although 4ꢀmethoxychrysene was deprotected successfully
to give chrysenol 1d, attempts to incorporate the N,Nꢀdiethyl carbamate group were futile, likely due to
steric crowding in the bay region.2,36 Interestingly, the desired carbamate 2d was obtained by the Mallory
photocyclization route (Scheme 1b), albeit as a minor component of the mixture with 2b, presumably also
due to steric reasons. Unfortunately, chrysenꢀ4ꢀyl N,NꢀdiethylꢀOꢀcarbamate (2d) could not be separated
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from carbamoylchrysene 2b by neither crystallization nor flash chromatography, and hence was not
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isolated (see Supporting Information).
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Molecules with phenolic rings which intersperse or bridge aromatic rings are available by the directed
remote metalation (DreM) reaction.23,37 Using this tactic, chrysenꢀ5ꢀyl N,NꢀdiethylꢀOꢀcarbamate (2e) was
prepared from the biaryl 4 (Scheme 1c).38 However, the intermediate chrysenol 1e was found to be highly
unstable in air and required handling under N2 and underwent rapid carbamoylation to give product 2e in
72% overall yield. An attempt to prepare the 6ꢀcarbamoyl chrysene by the DreM protocol was thwarted by
the fact that reaction of the requisite biaryl amide 5 afforded 5ꢀmethylꢀ11Hꢀbenzo[b]fluorenꢀ11ꢀone 6 rather
than the expected product (Scheme 1d).
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Scheme 1. Synthesis of Chrysenyl N,N-diethyl-O-carbamates (2a, 2b, 2c, 2e) and 5-methyl-11H-
benzo[b]fluoren-11-one (6)
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With four (2a-2c, 2e) of the six requisite regioisomeric chrysenyl N,NꢀdiethylꢀOꢀcarbamates in hand, DoM
studies were initiated and the results are summarized in Tables 1ꢀ4. Experiments were conducted under
standard metalation conditions (sꢀBuLi/TMEDA, 30 min) followed by electrophilic quench with a selection
of commonly used electrophiles.
Table 1. DoM reactions of Chrysene-1-yl N,N-diethyl-O-carbamates (2a)
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E+
E
Yield %
93
Product
Entry
1a,b
2a
7a
7b
7c
7d
7e
7f
TMSCl
I2
TMS
I
94
3a
Br2
Br
86
4a
C2Cl6
MeI
Cl
96
5c
Me
quant.
88
6c
Et2NCOCl
DMF
CONEt2
CHOd
7c
65
7g
b
a1) 1.1 equiv sꢀBuLi/ TMEDA, −78 °C, 30 min; 2) 1.5 equiv E+, −78 °C to rt., 1.5 h to 18 h; TMSCl was
c
added to the reaction mixture before sꢀBuLi; 1) 2 equiv sꢀBuLi/ TMEDA, −95 °C, 15 min; 2) 3 equiv E+, ꢀ
d
85 °C to rt., 3 ꢀ 4 h. Decarbamoylation occurred during the reaction with DMF to give the chrysenol
derivative.
In the first series (Table 1), chrysenꢀ1ꢀyl N,NꢀdiethylꢀOꢀcarbamate (2a), upon metalation and subsequent
quench with various electrophiles, afforded products 7a-g in excellent to modest yields. In the case of
using DMF as an electrophile (Entry 7, Table 1) decarbamoylation occurred to give 2ꢀ(hydroxy)chryseneꢀ
1ꢀcarbaldehyde (7g). In these reactions, no periꢀsubstituted (Cꢀ12) products were observed. Possible
reasons for the absence of periꢀlithiated product may be the rotational orientation of DMG (steric factor)
and the difference in the acidity of Cꢀ2 (electronꢀwithdrawing effect of DMG) and Cꢀ12 (peri) hydrogens.
Actually, Liꢀ1H HOESY NMR studies of complexes of lithiated 1ꢀnaphthol have shown that the peri (Cꢀ8)
7
hydrogen is in closer proximity to the prelithiated complex than Cꢀ2 hydrogen and exhibits a stronger
agostic interaction with the alkyl lithium base.39 However, possibly owing to the inductive strength of the
DMG, attempts to periꢀlithiate 1ꢀnapthamide by Clayden40, 41 were either futile or gave low yields.
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In pursuit of a molecule that will allow periꢀlithiation, 2ꢀ(trimethylsilyl)chryseneꢀ1ꢀyl N,NꢀdiethylꢀOꢀ
4
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43
carbamate (7a) in which the 2ꢀposition is blocked with a TMSꢀgroup,42,
was subjected to a second
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metalationꢀdeuteration sequence. As in the naphthyl case, starting material was recovered, conceivably
indicating inability to achieve high rotamer populations in which the carbonyl is oriented towards the periꢀ
hydrogen to effect deprotonation.
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In addition to the successful results (Table 1), benzaldehyde, pꢀnitrobenzaldehyde, 2ꢀmethoxyethoxy
methyl chloride and 2ꢀmethylbenzyl chloride electrophiles were tested but did not yield the expected
products and led to the recovery of unreacted starting material. While benzaldehyde was previously used
as an electrophile on benzyl18 and napthyl carbamates18, 25, it seemed to be unreactive with chrysenyl
carbamates.
Table 2. DoM reactions on Chrysene-2-yl N,N-diethyl-O-carbamate (2b)
Entry
1b,c
2c,e
3b
4b
5b
6f
7f
8f
9h
E+
Product
8a : 9a
10
E
Yield % (Ratio 8:9)a
27 (100 : 0)d
98%
TMSCl
TMSCl
I2
TMS
1,3ꢀdiTMS
8b : 9b
8c : 9c
8d : 9d
8e : 9e
8f : 9f
8g : 9g
8b
I
68 (57 : 43)
67 (56 : 44)
96 (59 : 41)
79 (54 : 46)
70 (75 : 25)
64 (68 : 32)
89 (100 : 0)
Br2
Br
C2Cl6
MeI
Cl
Me
Et2NCOCl
DMF
I2
CONEt2
CHOg
I
aThe products were isolated as mixture of two isomers and their ratio was determined by NMR analysis.
c
b1) 1.1 equiv. sꢀBuLi/ TMEDA, −78 °C, 30 min; 2) 1.5 equiv E+, −78 °C to rt., 1.5 ꢀ 18 h; TMSCl was
d
added to the reaction mixture before sꢀBuLi; yield by NMR analysis; e2.5 equiv sꢀBuLi/ TMEDA, 3 equiv
f
TMSCl; 1) 2 equiv sꢀBuLi/ TMEDA, −95 °C, 15 min; 2) 3 equiv E+, ꢀ85 °C to rt., 3 ꢀ 4 h;
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gDecarbamoylation occurred during reaction with DMF to give the chrysenol derivative; h1) 3 equiv. LiTMP,
−78 °C, 1.5 h, 2) 3 equiv. I2, −78 °C to rt, 5.5 h.
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Chrysenꢀ2ꢀyl N,NꢀdiethylꢀOꢀcarbamate (2b) was subjected to the same conditions as those used for
chryseneꢀ1ꢀyl N,NꢀdiethylꢀOꢀcarbamate (2a). As gleaned from Table 2, with the exception of the TMSCl
electrophile, little regioselectivity for the Cꢀ1 and Cꢀ3 positions was observed for which brief comment is
warranted. Rationalization of yields based on steric effects is difficult in view of the high complexity of the
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organolithium reactions involving aggregated lithiated species44 and indeterminate mechanism(s)37, 45, 46
.
Rate of substitution of lithiated species may be competitive with exchange with alternate deprotonation
sites as a function of electrophile. Thus, while the results with DMF and Et2NCOCl (entries 7 and 8) may
be rationalized based on steric effects, those with MeI and halogens are not consistent with a simple steric
argument and may be related to change in mechanism. The TMSCl quench reactions (entries 1 and 2)
were conducted under Martin conditions47 which promote, in part, baseꢀelectrophile in situ compatibility
which is reflected in the results: Using 1.5 equiv of TMSCl or large excess, both led to low yield of monoꢀ
silylated product 8a with the recovery of unreacted 2b, while 2.5 equiv of baseꢀelectrophile combination
afforded almost quantitative yield of diꢀsilylated product 10. As observed, excess of base followed by
quench with excess electrophile in all other cases (entries 5ꢀ7) led to monosubstituted products. As a
rationalization of these results, a sequential deprotonationꢀsilylation is suggested in which decomposition
of TMSCl is sufficiently slow to allow double silylation of the derived Cꢀ3 anion.18 Synthetically, the diꢀ
silylation result (entry 2) is similar to that achieved in benzamide18,42,48 and naphthyl 2ꢀOꢀcarbamate25
series and may be of synthetic value. The lack of Cꢀ1 vs Cꢀ3 regioselectivity using sꢀBuLi/TMEDA may be
improved by change to a more sterically demanding base. Thus, using LiTMP metalation conditions and I2
quench, the carbamate 2b afforded 3ꢀiodochrysenꢀ2ꢀyl N,NꢀdiethylꢀOꢀcarbamate (8b) as a single
regioisomer in 89% yield. An analogous selectivity was observed in experiments conducted on naphthyl 2ꢀ
carbamate.25
Table 3. DoM reactions on Chrysene-3-yl N,N-diethyl-O-carbamates (2c)
Entry
1a,b
2a
E+
Product
11a
E
Yield %
89
TMSCl
I2
TMS
I
11b
91
3a
4a
Br2
11c
Br
Cl
57c
70c
C2Cl6
11d
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5d
6d
7d
MeI
11e
11f
Me
96
88
72
Et2NCOCl
CONEt2
CHOe
DMF
11g
a1) 1.1 equiv sꢀBuLi/ TMEDA, −78 °C, 30 min; 2) 1.5 equiv E+, −78 °C to rt., 1.5 h to 18 h; bTMSCl was
added to the reaction mixture before sꢀBuLi; cYield by NMR analysis; d1) 2 equiv sꢀBuLi/ TMEDA, −95 °C,
8
9
e
15 min; 2) 3 equiv E+, ꢀ85 °C to rt., 3 ꢀ 4 h; Decarbamoylation occurred during reaction with DMF to give
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the chrysenol derivative.
As expected, based on steric effects of the bayꢀregion,2, 36 chryseneꢀ3ꢀyl N,NꢀdiethylꢀOꢀcarbamate (2c)
afforded, using selected electrophiles, product 11a-11g with complete regioselectivity. The Br2 quench
experiments (entry 3) required careful control of addition to avoid formation of dibrominated product
(confirmed by HRMS analysis) and a complex mixture of products. Attempts to effect Cꢀ4 metalation of 2ꢀ
(trimethyl silyl)chrysenꢀ3ꢀyl N,NꢀdiethylꢀOꢀcarbamate (11a) also turned futile with the recovery of starting
material when MeOD and MeI were used as electrophiles (HRMS analysis, see Supporting Information).
Table 4. DoM reactions on Chrysen-5-yl N,N-diethyl-O- carbamate (2e)
Entry
1a,b
2c
E+
T °C
−78
Yield %
75
TMSCl
ꢀ
−100
−100
79
3d
Br2
71
b
a1) 1.1 mmol sꢀBuLi/ TMEDA, −78 °C, 30 min, 2) 1.5 mmol E+, −78 °C to rt; TMSCl was added to the
c
d
reaction mixture before sꢀBuLi; 1.1 mmol sꢀBuLi/ TMEDA, −100 °C, 1h; 1) 1.1 mmol sꢀBuLi/ TMEDA,
−100 °C, 10 min; 2) 1.5 equiv E+, −100 °C to rt.
Chrysenꢀ5ꢀyl N,NꢀdiethylꢀOꢀcarbamate (2e) (Table 4), posits an interesting case since the opposite bayꢀ
hydrogen in Cꢀ4 position is expected to show strong hindrance in the orientation of the carbamoyl group
towards the bay region. In the event, metalation under in situ TMSCl quench conditions at either −78 °C
under (entry 1) or at −100°C (entry 2) resulted in extremely fast AoF rearrangement to cleanly afford
amide 12. In addition, an attempt to quench the reaction with Br2 at −100 °C (entry 3) also gave compound
12. The metalation of the 1ꢀ and 2ꢀ and 3ꢀ, 5ꢀsubstituted chrysenyl derivatives showed individual
characteristic color changes upon lithiation (see Supporting Information). The failure to inhibit the AoF
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rearrangement by lowering the temperatures and variation of lithiation time suggests that significant steric
and electronic factors49, 50 of the Kꢀregion of chrysene are involved.
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CONCLUSION
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In conclusion, we have shown new DoM strategy using the powerful OCONEt2 DMG for the chrysenyl Oꢀ
carbamates 2a, 2b, 2c, 2e which leads to the efficient synthesis of disubstituted derivatives (Tables 1ꢀ4).
Compound 2b (Table 2) shows essentially no regioselective preference for the two ortho sites under
standard sꢀBuLi/TMEDA conditions but indicates that LiTMP is a promising base for regioselectivity
improvement. The availability of periꢀmetalation site is of no consequence for the DoM reaction (2a, Table
1) either directly or with 2ꢀTMS protection. However, the Kꢀregion influence, of significance in
consideration of carcinogenic effects51, 52 affects the reactivity of the DoM reactions of 2c (Table 3) and 2e
(Table 4) perhaps by combination of steric and electronic effects on the orientation of the carbamate group
as a function of the rotational barriers. The present work provides an expansion of the DoM methodology
for the preparation of substituted chrysenes (7a-7g, 8a-8g, 9a-9g, 10, 11a-11g, 12). The utility for the
DoM strategy described herein for the synthesis of other PAH type molecules may be anticipated.
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EXPERIMENTAL SECTION
General Methods. All experiments were carried out in ovenꢀdried glassware, using septa and syringes
under dryꢀN2 atmosphere and monitored by TLC (Merck silica gel 60 F254 plates) using UV light at 254 nm
for detection. Purchased anhydrous solvents and chemical reagents were used without further purification,
unless otherwise specified. sꢀBuLi was titrated periodically before use. The reagents were distilled and
stored over molecular sieves before use. The products were purified by flash chromatography using silica
1
gel (particle size: 40ꢀ60 ꢁm. 60Å) with PE or heptane and EtOAc. H and 13C NMR spectra were either
recorded on Bruker Avance 300 MHz or 400 MHz spectrometers with chemical shifts reported in ppm
relative to internal TMS (δ = 0) or CHCl3 (δ = 7.26), CDCl3 (δ = 77.0). The multiplicities were recorded as
singlet, s; doublet, d; triplet t; double doublet, dd; doublet of triplet, dt; triplet of doublet, td; quartet, q;
multiplet, m; apparent, app; broad, br. IR spectra was obtained from KBr discs on an Agilent Cary 630
FTIR spectrometer. Mass spectra were obtained from ESIꢀTOF instruments at the University of Bergen
and the University of Tromsø, Norway. All melting points were measured on Stuart Scientific melting point
apparatus SMP3 and are uncorrected.
Synthesis of Chrysenols. Chrysenols 1aꢀ1c were synthesized by oxidative photo cyclization of stilbenes
followed by demethylation with BBr3, as previously described.34
General Procedure for the Synthesis of Chrysenyl N,N-diethyl-O-carbamate from Chrysenols. The
chrysenol (1 mmol) in THF (2 mL) was added to a suspension of NaH (1.2 mmol) in THF (2 mL) at 0 °C.
The reaction mixture was allowed to stir for 15 min and then warmed to rt before dropꢀwise addition of
N,Nꢀdiethylcarbamoyl chloride (1.1 mmol). The mixture was stirred until complete reaction and quenched
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with aq satd NH4Cl solution (10 mL). The solution was extracted with Et2O or EtOAc (3 x 10 mL) and the
combined organic phase was washed with brine (3 x 10 mL), dried (MgSO4), evaporated to dryness and
the residue purified by gradient flash column chromatography (EtOAc and hexane).
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Chrysen-1-yl N,N-diethyl-O-carbamate (2a). Following the general procedure, the reaction mixture was
stirred for 13 h. Normal workꢀup (extraction with Et2O) and purification by flash column chromatography
(EtOAc:hexane 1:5) afforded product 2a (886 mg , 95%) from chrysenꢀ1ꢀol (1a) (668 mg, 2.73 mmol), as a
white shiny powder, mp. 172.0−173.0 °C (EtOAc); 1H NMR (400 MHz, CDCl3) δ 8.78 (d, J = 8.2 Hz, 1H),
8.76 (d, J = 9.2 Hz, 1H), 8.70 (d, J = 9.1 Hz, 1H), 8.65 (d, J = 8.6 Hz, 1H), 8.13 (d, J = 9.2 Hz, 1H), 8.01
(d, J = 9.0 Hz, 1H), 8.00 (dd, J = 1.3, 7.8 Hz, 1H), 7.74−7.63 (m, 3H), 7.46 (d, J = 7.7 Hz, 1H), 3.68 (q, J =
6.9 Hz, 2H), 3.50 (q, J = 6.9 Hz, 2H), 1.45 (t, J = 6.9 Hz, 3H), 1.30 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz,
CDCl3) δ 154.3, 147.9, 132.2, 132.0, 130.4, 128.5, 128.2, 128.1, 127.6, 126.7, 126.5, 126.3, 126.0, 123.1,
121.7, 121.4, 120.4, 120.2, 118.9, 42.4, 42.1, 14.5, 13.5; FTIR (KBr, cmꢀ1) 2976, 2936, 1716, 1596, 1409,
1273, 1259; HRMS (ESI) m/z [M + Na]+ for formula C23H21NNaO2: calcd, 366.1470; found 366.1477.
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Chrysen-3-yl N,N-diethyl-O-carbamate (2c). Following the general procedure, the reaction mixture was
stirred for 14 h. Normal workꢀup (extraction with Et2O) and purification by flash column chromatography
(EtOAc:hexane 1:5, with 10% DCM) afforded product 2c (7.76 g , 91%) from chrysenꢀ3ꢀol (1c) (6.04 g,
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24.70 mmol), as a white shiny powder, mp. 121.5−122.5 °C (EtOAc); H NMR (300 MHz, CDCl3) δ 8.77
(d, J = 8.2 Hz, 1H), 8.67 (d, J = 9.0 Hz, 1H), 8.61 (d, J = 9.2 Hz, 1H), 8.48 (app d, J = 2.0 Hz 1H), 7.98 (d,
J = 8.7 Hz, 2H), 7.97 (d, J = 8.9 Hz, 2H) 7.72−7.68 (m, 1H), 7.65−7.61 (m, 1H), 7.44 (dd, J = 2.2, 8.7 Hz,
1H), 3.55 (br. q, J = 6.8 Hz, 2H), 3.46 (br. q, J = 6.8 Hz, 2H) 1.35 (br. t, J = 6.9 Hz, 3H), 1.26 (br. t, J = 7.0
Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 154.4, 150.2, 132.2, 131.4, 130.5, 129.7, 129.6, 128.5, 128.4,
127.9, 127.2, 126.9, 126.6, 126.4, 123.2, 121.6, 121.4, 120.6, 115.0, 42.3, 42.0, 14.3, 13.4; FTIR (KBr,
cmꢀ1) 2975, 1715, 1618, 1596, 1470, 1456, 1418, 1376, 1313, 1272, 1248; HRMS (ESI) m/z [M + Na]+ for
formula C23H21NNaO2: calcd, 366.1470; found 366.1477.
Chrysen-2-yl N,N-diethyl-O-carbamate (2b).To a solution of 2ꢀmethoxychrysene (833 mg, 3.23 mmol) in
DCM (30 mL) was added BBr3 (4.84 mL, 4.84 mmol) at 0 °C. After stirring for 21 h, the reaction mixture
was quenched with water (14 mL). The aqueous layer was extracted with EtOAc (3 x 30 mL), before the
combined organic phase was dried over MgSO4 and concentrated in vacuo. The crude chrysenꢀ2ꢀol (1b)
(3.23 mmol) in THF (15 mL) was added to a suspension of NaH (193 mg, 4.83 mmol) in THF (10 mL) at 0
°C. After 15 min. of stirring the mixture was warmed to rt before N,Nꢀ diethylcarbamoyl chloride (0.42 mL,
3.31 mmol) was added, and the reaction mixture was stirred overnight (21 h). After normal workꢀup
(extraction with EtOAc), followed by flash column chromatography (EtOAc:PE 1:2, with 10% DCM),
product 2b (936 mg , 85% ꢀ two step) was obtained as a white shiny powder, mp. 189.0−190.0 °C
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(EtOAc); H NMR (300 MHz, CDCl3) δ 8.76 (d, J = 8.9 Hz, 1H), 8.72 (d, J = 9.3 Hz, 1H), 8.67 (d, J = 9.2
Hz, 1H), 8.61−7.94 (m, 3H), 7.76 (app d, J = 2.3 Hz, 1 H), 7.73−7.61 (m, 2 H), 7.51 (dd, J = 2.4, 9.0 Hz, 1
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H), 3.55−3.45 (m, 4H), 1.36−1.27 (m, 6H); 13C NMR (75 MHz, CDCl3) δ 154.3, 149.8, 132.9, 132.0, 130.5,
128.5, 128.2, 128.0, 127.8, 127.5, 126.9, 126.7, 126.3, 124.5, 123.0, 121.9, 121.7, 121.2, 119.4, 42.3,
42.0, 14.3, 13.4; FTIR (KBr, cmꢀ1) 2978, 1703, 1522, 1474, 1422, 1364, 1272; HRMS (ESI) m/z [M + Na]+
for formula C23H21NNaO2: calcd, 366.1470; found 366.1477.
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Synthesis of Chrysenyl N,N-diethyl-O-carbamates by Directed remote Metalation (DreM).
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Chrysen-5-yl N,N-diethyl-O-carbamate (2e). To a solution of diisopropylamine (DIPA) (1.26 mL, 8.99
mmol) in THF (15 mL) was added nꢀBuLi (4.26 mL, 8.95 mmol) at ꢀ5 ºC. Biphenyl 438 (1.22 g, 3.85 mmol)
in THF (8 mL) was added dropwise, and the reaction mixture stirred for 70 min at rt. Normal workup gave
the chrysenꢀ5ꢀol (1e) as a yellow solid in a complete reaction according to TLC. 1e (3.85 mmol) was
added to a suspension of NaH (0.258 g, 6.45 mmol) in THF (7 mL) at 0 ºC. N,Nꢀdiethylcarbamoyl chloride
(0.5 mL, 3.95 mmol) was added at rt, and the reaction mixture stirred at rt for 18 h. Normal workup
followed by flash column chromatography (EtOAc:hexane 1:6) afforded product 2e as white shiny powder
(953 mg, 72%), mp. 142.5−143.5 °C (EtOAc); 1H NMR (400 MHz, CDCl3) δ 9.14ꢀ9.11 (m, 1H), 8.73 (d, J =
9.0 Hz, 2 H), 7.99 (d, J = 8.7 Hz, 1H), 7.97−7.95 (m, 1H), 7.92−7.89 (m, 1H), 7.68 (s, 1H), 7.67−7.57 (m,
4H), 3.78 (q, J = 7.0 Hz, 2H), 3.47 (q, J = 7.0 Hz, 2H), 1.47 (t, J = 7.1 Hz, 3H), 1.25 (t, J = 7.0 Hz, 3H); 13
C
NMR (100 MHz, CDCl3) δ 154.1, 147.6, 133.0, 131.9, 131.0, 129.5, 128.9, 128.7, 128.4, 127.8, 126.8,
126.5, 126.4, 126.2, 126.15, 123.5, 123.3, 121.3, 120.5, 42.2, 41.9, 14.5, 13.4; FTIR (KBr, cmꢀ1) 2979,
2932, 1702, 1522, 1474, 1422, 1380, 1272; HRMS (ESI) m/z [M + Na]+ for formula C23H21NNaO2: calcd,
366.1470; found 366.1471.
5-Methyl-11H-benzo[b]fluoren-11-one (6). Lithium diisopropylamine (LDA) (4.65 mL, 6.46 mmol, 1.39 M in
THF) was added to a precooled solution of biphenyl 5 (661 mg, 2.08 mmol) at 0 °C. The reaction mixture
was stirred at rt for 1 h, before tertꢀbutyldimethylsilyl chloride (1.0 M, 5.7 mL, 5.7 mmol) was added. The
reaction mixture was stirred for 18 h and after normal workꢀup (extraction with Et2O), followed by flash
column chromatography (EtOAc:PE 1:9) afforded compound 6 (201 mg, 40%) of 5ꢀmethylꢀ
1
11Hbenzo[b]fluorenꢀ11ꢀone (6) as an orange solid, mp. N/A; H NMR (CDCl3, 300 MHz) δ 8.38−8.33 (m,
1H), 7.96−7.91 (m, 1H), 7.86 (d, J = 7.5 Hz, 1H), 7.60−7.51 (m, 3H), 7.47 (s, 1H), 7.46−7.40 (m, 1H),
7.25−7.20 (m, 1H), 2.63 (s, 3H); 13C NMR (CDCl3, 75 MHz) δ 194.7, 145.1, 141.0, 136.7, 136.4, 134.3,
131.26, 131.2, 128.8, 128.2, 128.0, 127.1, 125.6, 125.2, 123.8, 122.9, 120.5, 19.9; FTIR (KBr, cmꢀ1) 3049,
2981, 1709, 1621, 1606, 1583, 1468, 1424, 1400, 1272; HRMS (ESI) m/z [M + H]+ for formula C18H13O:
calcd, 245.0961; found 245.0959.
General procedure for the DoM Reaction on Chrysenyl O-carbamates.
To a solution of chrysenyl N,Nꢀdiethyl carbamate (1 mmol) dissolved in THF (2 mL) was added dry
TMEDA (1.1 mmol). The solution was cooled to −78 °C before sꢀBuLi (1.1 mmol) was added slowly in
dropꢀwise manner. After stirring for 30 min, the electrophile (1.5 mmol) was added and the reaction
mixture was stirred and allowed to reach rt over 1.5 h to 18 h. The reaction mixture was quenched with aq
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satd NH4Cl solution (5 mL). The solution was extracted with EtOAc (3 x 15 mL) and the organic layer was
washed with brine (3 x 15 mL) and dried (MgSO4) followed by evaporation to dryness. The residue was
purified by gradient flash column chromatography (EtOAc and PE) to obtain pure product.
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2-(Trimethysilyl)chrysene-1-yl N,N-diethyl-O-carbamate (7a). According to the general procedure, 2a (187
mg, 0.54 mmol) in THF (3 mL) was treated with sꢀBuLi (0.51 mL, 0.60 mmol), TMEDA (0.09 mL, 0.60
mmol) and TMSCl (0.10 mL, 0.79 mmol) at −78 °C for 1.5 h. Normal workup, followed by flash column
chromatography (EtOAc:hexane 1:6) afforded product 7a (209 mg, 93%) as a beige solid, mp.
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158.0−159.5 °C (EtOAc); H NMR (400 MHz, CDCl3) δ 8.76−8.72 (m, 2H), 8.69 (d, J = 9.1 Hz, 1H), 8.63
(d, J = 8.4 Hz, 1H), 7.99 (d, J = 9.1 Hz, 1H), 7.98 (dd, J = 1.0, 7.8 Hz, 1H), 7.91 (d, J = 9.3 Hz, 1H), 7.76
(d, J = 8.4 Hz, 1H), 7.71−7.67 (m, 1H), 7.64−7.61 (m, 1H), 3.85−3.39 (m, 4H), 1.47 (t, J = 7.1 Hz, 3H),
1.27 (t, J = 7.1 Hz, 3H), 0.40 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 154.4, 153.2, 133.0, 132.3, 131.4,
130.4, 130.4, 129.0, 128.5, 128.3, 128.1, 127.5, 126.7, 126.5, 126.0, 123.2, 121.8, 121.5, 120.4, 120.35,
42.0, 41.8, 14.5, 13.3, 0.0; FTIR (KBr, cmꢀ1) 2971, 1709, 1615, 1584, 1474, 1418, 1390, 1349, 1270,
1247; HRMS (ESI) m/z [M + Na]+ for formula C26H29NNaO2Si: calcd, 438.1865; found 438.1860.
2-Iodochrysen-1-yl N,N-diethyl-O-carbamate (7b). According to the general procedure, 2a (102 mg, 0.30
mmol) in THF (2.2 mL) was treated with sꢀBuLi (0.26 mL, 0.33 mmol), TMEDA (0.05 mL, 0.33 mmol) and
iodine in THF (1 M, 0.6 mL, 0.6mmol) at −78 °C, and warmed to rt over 5.5 h. Normal workup, followed by
flash column chromatography (EtOAc:hexane 1:6) afforded product 7b (131 mg, 94%) as a beige solid,
mp. 221.0−222.0 °C (EtOAc); 1H NMR (400 MHz, CDCl3) δ 8.69 (d, J = 7.8 Hz, 1H), 8.54 (d, J = 9.0 Hz,
1H), 8.30 (d, J = 8.8 Hz, 1H), 7.98−7.92 (m, 4H), 7.69−7.66 (m, 1H), 7.63−7.60 (m, 1H), 3.76−3.47 (m,
4H), 1.48 (t, J = 7.0 Hz, 3H), 1.30 (t, J = 7.0 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 152.7, 148.8, 135.3,
132.2, 131.7, 130.3 (2C), 128.5, 128.2, 127.9, 127.3, 126.8, 126.6, 123.1, 122.7, 122.3, 121.0, 120.4,
89.2, 42.5, 42.3, 14.7, 13.4; FTIR (KBr, cmꢀ1) 2972, 1723, 1587, 1469, 1419, 1392, 1367, 1270; HRMS
(ESI) m/z [M + Na]+ for formula C23H20INNaO2: calcd, 492.0436; found 492.0434.
2-Bromochrysen-1-yl N,N-diethyl-O-carbamate (7c). According to the general procedure, 2a (141 mg, 0.41
mmol) in THF (2.8 mL) was treated sequentially with sꢀBuLi (0.39 mL, 0.46mmol), TMEDA (0.07 mL, 0.47
mmol) and Br2 (19.25 M, 0.03 mL, 0.58 mmol) at −78 °C, and warmed to rt over 16 h. Normal workup,
followed by flash column chromatography (EtOAc:hexane 1:5) afforded product 7c (149 mg, 86%) as a
beige solid, mp. 211.0−212.0 °C (EtOAc); 1H NMR (300 MHz, CDCl3) δ 8.73−8.69 (m, 2H), 8.55 (d, J = 9.0
Hz, 1H), 8.44 (d, J = 9.1 Hz, 1H), 8.00 (d, J = 9.4 Hz, 1H), 7.95 (d, J = 8.2 Hz, 2H), 7.79 (d, J = 8.5 Hz,
1H), 7.71−7.60 (m, 2H), 3.73−3.66 (m, 2H), 3.49 (app. d, J = 6.1 Hz, 2H), 1.47 (t, J = 7.0 Hz, 3H), 1.29 (t,
J = 7.0 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 152.9, 145.4, 132.2, 130.9, 130.3, 129.9, 128.5, 128.2,
127.9, 127.88, 127.8, 126.9, 126.6, 123.1, 122.8, 122.0, 121.0, 120.2, 114.6, 42.6, 42.3, 14.5, 13.4; FTIR
(KBr, cmꢀ1) 2975, 1725, 1591, 1471, 1417, 1394, 1267, 695; HRMS (ESI) m/z [M + Na]+ for formula
C23H20BrNNaO2: calcd, 444.0575; found 444.0579.
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2-Chlorochrysen-1-yl N,N-diethyl-O-carbamate (7d). According to the general procedure, 2a (100 mg,
0.29 mmol) in THF (2.2 mL) was treated with sꢀBuLi (0.25 mL, 0.31 mmol), TMEDA (0.05 mL, 0.33 mmol)
and Cl3CCCl3 (139 mg, 0.59 mmol) in THF (1 mL) at −78 °C, and warmed to rt over 6 h. Normal workup,
followed by flash column chromatography (EtOAc:hexane 1:6) afforded product 7d (108 mg, 96%) as a
white solid, mp. 218.5−219.5 °C (EtOAc); 1H NMR (300 MHz, CDCl3) δ 8.74−8.69 (m, 2H), 8.56−8.49 (m,
2H), 8.02 (d, J = 9.3 Hz, 1H), 7.95 (d, J = 8.4 Hz, 2H), 7.71−7.60 (m, 3H), 3.68 (q, J = 7.0 Hz, 2H), 3.49 (q,
J = 7.0 Hz, 2H), 1.46 (t, J = 7.1 Hz, 3H), 1.29 (t, J = 7.2 Hz, 3H); 13C NMR (75 MHz, CDCl3) δ 153.0,
143.9, 132.1, 130.3, 128.5, 128.1, 127.9, 127.8, 127.7, 127.3, 126.9, 126.6, 124.9, 123.0, 122.8, 121.6,
121.0, 120.0, 42.6, 42.3, 14.4, 13.4; FTIR (KBr, cmꢀ1) 2976, 2933, 1724, 1594, 1471, 1419, 1397, 1382,
1268, 702; HRMS (ESI) m/z [M + Na]+ for formula C23H20ClNNaO2: calcd, 400.1080; found 400.1099.
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2-Methylchrysen-1-yl N,N-diethyl-O-carbamate (7e). According to the general procedure, 2a (111 mg, 0.32
mmol) in THF (2.2 mL) was treated with sꢀBuLi (0.57 mL, 0.65 mmol), TMEDA (0.10 mL, 0.65 mmol) and
MeI (0.06 mL, 0.97 mmol) at −95 °C, and warmed to rt over 4 h. Normal workup, followed by flash column
chromatography (EtOAc:PE 1:8) compound 7e was isolated as a brown solid (116 mg, 100%), mp
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179.5−180.6 °C (EtOAc); H NMR (400 MHz, CDCl3) δ 8.78ꢀ8.74 (m, 2H), 8.64 (d, J = 9.0 Hz, 1H), 8.53
(d, J = 8.7 Hz, 1H), 8.06 (d, J = 9.3 Hz, 1H), 8.00−7.95 (m, 2H), 7.73−7.69 (m, 1H), 7.66−7.62 (m, 1H),
7.55 (d, J = 8.6 Hz, 1H), 3.70 (q, J = 6.9 Hz, 2H), 3.53 (q, J = 6.9 Hz, 2H), 2.48 (s, 3H), 1.47 (t, J = 7.05
Hz, 3H), 1.33 (t, J = 7.04 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 153.7, 145.6, 131.9, 130.4, 130.2, 129.1,
128.4, 128.1, 127.7, 127.5, 127.3, 126.5, 126.4, 126.1 122.9, 121.7, 121.2, 120.4, 120.0, 42.3, 42.0, 16.4,
14.5, 13.4; FTIR (KBr, cmꢀ1) 2980, 1714, 1475, 1418, 1397, 1271, 1256, 1184; HRMS (ESI) m/z [M + Na]+
for formula C24H23NNaO2 : calcd, 380.1626; found, 380.1621.
2-(N,N-Diethyl carbamoyl)chrysen-1-yl N,N-diethyl-O-carbamate (7f). According to the general procedure,
2a (100 mg, 0.29 mmol) in THF (2.2 mL) was treated with sꢀBuLi (0.52 mL, 0.58 mmol), TMEDA (0.09 mL,
0.58 mmol) and Et2NCOCl (0.11 mL, 0.87 mmol) at −95 °C, and warmed to rt over 4 h. Normal workup,
followed by flash column chromatography (EtOAc:PE 1:2) afforded compound 7f as an offꢀwhite solid (113
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mg, 88%), mp. 183.0−184.5 °C (EtOAc); H NMR (400 MHz, CDCl3) δ 8.77−8.72 (m, 2H), 8.65−8.63 (m,
2H), 8.06 (d, J = 9.3 Hz, 1H), 7.97 (br. d, J = 8.6 Hz, 1H), 7.71−7.67 (m, 1H), 7.65−7.61 (m, 1H), 7.57 (d, J
= 8.6 Hz, 1H), 3.64−3.43 (m, 8H), 1.42 (t, J = 7.1 Hz, 3H), 1.29−1.23 (m, 6H), 1.12 (t, J = 7.1 Hz, 3H); 13
C
NMR (100 MHz, CDCl3) δ 167.7, 153.5, 144.1, 132.2, 131.8, 130.2, 128.4, 128.37, 127.9, 127.75, 127.7,
126.8, 126.7, 126.6, 123.7, 123.0, 122.3, 121.7, 120.7, 120.4, 42.8, 42.4, 42.3, 38.5, 14.4, 13.8, 13.4,
12.6; FTIR (KBr, cmꢀ1) 2975, 2934, 1716, 1633, 1472, 1420, 1383, 1366, 1270; HRMS (ESI) m/z [M + Na]+
for formula C28H30N2NaO3: calcd, 465.2154 ; found, 465.2140.
2-(Hydroxy)chrysene-1-carbaldehyde (7g). According to the general procedure, 2a (103 mg, 0.30 mmol) in
THF (2.2 mL) was treated with sꢀBuLi (0.53 mL, 0.60 mmol), TMEDA (0.09 mL, 0.60 mmol) and DMF
(0.07 mL, 0.90 mmol) at −95 °C, and warmed to rt over 3.5 h. Normal workup, followed by flash column
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179.0−180.6 °C (Acetone); H NMR (400 MHz, CDCl3) δ 12.48 (s, 1H), 10.06 (s, 1H), 8.82−8.77 (m, 2H),
8.63 (d, J = 9.1 Hz, 1H), 8.59 (d, J = 9.3 Hz, 1H), 8.30 (d, J = 8.8 Hz, 1H), 8.02 (d, J = 9.1 Hz, 1H), 8.00
(dd, J = 1.4, 7.9 Hz, 2H), 7.72, (d, J = 8.8 Hz, 1H), 7.77−7.67 (m, 2H); 13C NMR (100 MHz, CDCl3) δ
196.3, 161.2, 135.8, 132.7, 131.2, 130.2, 128.6, 127.9, 127.86, 127.4, 127.39, 127.0, 123.6, 122.7, 121.7,
121.6, 121.4, 115.1, 114.7; FTIR (KBr, cmꢀ1) 1646, 1627, 1588, 1460, 1384, 1320; HRMS (ESI) m/z [M ꢀ
H]ꢀ for formula C19H11O2: calcd, 271.0759; found, 271.0764.
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3-Iodochrysen-2-yl N,N-diethyl-O-carbamate (8b) and 1-Iodochrysen-2-yl N,N-diethyl-O-carbamate (9b).
According to the general procedure, 2b (139 mg, 0.41 mmol) in THF (10 mL) was treated with sꢀBuLi
(0.43 mL, 0.43 mmol), TMEDA (0.07 mL, 0.46 mmol) and iodine (0.6 mL, 0.6 mmol, 1.0 M in THF) at −78
°C, and warmed to rt over 5.5 h. Normal workup, followed by flash column chromatography
(EtOAc:hexane 1:6) afforded a beige solid as a mixture of 8b and 9b (130 mg, 68%, 57:43), mp.
171.5−173.0 °C (EtOAc); 1H NMR (400 MHz, CDCl3) δ 9.16 (s, 1H – 8b), 8.71 (d, J = 9.0 Hz, 1H – 8b, 1H
– 9b), 8.70 (d, J = 9.2 Hz, 1H ꢀ 9b), 8.69−8.67 (m, 1H – 9b), 8.64 (d, J = 9.1 Hz, 1H – 8b), 8.58 (d, J = 9.1
Hz, 1H – 9b), 8.50 (d, J = 9.1 Hz, 1H – 8b), 8.32 (d, J = 9.3 Hz, 1H – 9b), 7.96−7.93 (m, 1H – 8b, 1H –
9b), 7.77 (s, 1H – 8b), 7.71−7.59 (m, 1H – 8b, 1H – 9b), 7.50 (d, J = 9.0 Hz, 1H – 9b), 3.66−3.58 (m, 2H –
8b, 2H – 9b), 3.46 (q, J = 7.0 Hz, 2H – 8b, 2H – 9b), 1.42−1.37 (m, 3H – 8b , 3H – 9b), 1.27 (t, J = 7.0 Hz,
3H – 8b, 3H – 9b); 13C NMR (100 MHz, CDCl3) δ 153.22, 153.2, 150.9, 149.0, 134.7, 134.1, 132.7, 132.1,
132.08, 130.9 (2C), 130.3, 130.2, 129.6, 128.9, 128.5, 128.46, 128.1, 128.0 (2C), 127.8, 126.9, 126.8,
126.76, 126.6, 126.5, 126.47, 124.7, 123.5, 123.05, 123.0, 122.4, 121.1, 120.8, 120.7, 96.0, 90.7, 42.4,
42.3, 42.1 (2C), 14.5, 14.4, 13.4 (2C); FTIR (KBr, cmꢀ1) 2978, 2933, 1713, 1591, 1473, 1416, 1380, 1313,
1272; HRMS (ESI) m/z [M + Na]+ for formula C23H20INNaO2: calcd, 492.0436; found 492.0434.
3-Iodochrysen-2-yl N,N-diethyl-O-carbamate (8b). The compound 2b (100 mg, 0.29 mmol) in THF (3 mL)
was treated with LiTMP (0.87 mmol prepared in situ by adding 0.87 mmol of n-BuLi to 0.96 mmol of
2,2,6,6ꢀTMP in 1 mL THF at 0 °C) for 1.5 h and quenched with I2 (0.87 mL , 0.87 mmol, 1.0 M in THF) at
−78 °C, and warmed to rt over 5.5 h. Normal workup, followed by flash column chromatography
(EtOAc:hexane 1:6) afforded 8b (116 mg, 89%) as a white solid, mp. 171.8−172.8 °C (EtOAc); 1H NMR
(400 MHz, CDCl3) δ 9.09 (s, 1H), 8.61 (d, J = 9.0 Hz, 1H), 8.54 (d, J = 9.1 Hz, 1H), 8.39 (d, J = 9.1 Hz,
1H), 7.92 (app dd, J = 1.2, 7.7 Hz, 1H), 7.87 (d, J = 9.1 Hz, 1H), 7.78−7.75 (m, 1H), 7.75 (s, 1H),
7.66−7.58 (m, 2H), 3.61 (q, J = 7.2 Hz, 2H), 3.50 (q, J = 7.2 Hz, 2H), 1.41 (t, J = 7.1 Hz, 3H), 1.31 (t, J =
7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 153.1, 148.9, 134.5, 132.5, 131.9, 130.1, 129.4, 128.4, 127.8,
126.7, 126.5, 126.4, 126.3, 122.9, 122.3, 120.6, 120.57, 90.6, 42.3, 42.1, 14.4, 13.3; FTIR (KBr, cmꢀ1)
2974, 1714, 1473, 1416, 1380, 1244; HRMS (ESI) m/z [M + Na]+ for formula C23H20INNaO2: calcd,
492.0436; found 492.0434.
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3-Bromochrysen-2-yl N,N-diethyl-O-carbamate (8c) and 1-Bromochrysen-2-yl N,N-diethyl-O-carbamate
(9c). According to the general procedure, 2b (89 mg, 0.26 mmol) in THF (6 mL) was treated with sꢀBuLi
(0.38 mL, 0.27 mmol), TMEDA (0.04 mL, 0.27 mmol) and Br2 (0.04 mL, 0.77 mmol) at −78 °C, and
warmed to rt over 5 h. Normal workup, followed by flash column chromatography (EtOAc:hexane 1:4)
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afforded a mixture of 8c and 9c ( 73 mg, 67%, 56:44) as a beige solid, mp. 198.5−200.0 °C (EtOAc); H
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NMR (400 MHz, CDCl3) δ 8.91 (s, 1H – 8c), 8.70−8.65 (m, 1H – 8c, 3H – 9c), 8.61 (d, J = 9.2 Hz, 1H –
8c), 8.53 (d, J = 9.0 Hz, 1H – 9c), 8.45 (d, J = 9.0 Hz, 1H – 8c), 8.38 (d, J = 9.4 Hz, 1H – 9c), 7.95−7.91
(m, 2H – 8c, 2H – 9c), 7.82 (d, J = 9.3 Hz, 1H – 8c), 7.81 (s, 1H – 8c), 7.71−7.60 (m, 2H – 8c, 2H – 9c),
7.54 (d, J = 9.1 Hz, 1H – 9c), 3.63−3.58 (m, 2H – 8c, 2H – 9c), 3.51−3.46 (q, J = 6.9 Hz, 2H – 8c, 2H –
9c), 1.43−1.39 (m, 3H – 8c, 3H –9c), 1.31−1.28 (m, 3H – 8c, 3H – 9c); 13C NMR (100 MHz, CDCl3) δ
153.2, 153.19, 147.4, 146.5, 132.0, 131.8, 131.5, 130.2, 130.1, 129.2, 129.1, 128.5, 128.4, 128.1, 127.94,
127.9, 127.8, 127.77, 127.7, 126.9, 126.8, 126.7, 126.6, 126.5, 126.3, 125.5, 123.4, 123.0, 122.99,
122.95, 122.6, 122.2, 121.7, 121.0, 120.7, 116.24, 116.21, 42.4 (2C), 42.1 (2C), 14.3, 14.2, 13.4 (2C);
FTIR (KBr, cmꢀ1) 2978, 2933, 1726, 1472, 1417, 1381, 1273, 1249; HRMS (ESI) m/z [M + Na]+ for formula
C23H20BrNNaO2: calcd, 444.0575; found 444.0589.
3-Chlorochrysen-2-yl N,N-diethyl-O-carbamate (8d) and 1-Chlorochrysen-2-yl N,N-diethyl-O-carbamate
(9d). According to the general procedure, 2b (130 mg, 0.38 mmol) in THF (6 mL) was treated with sꢀBuLi
(0.44 mL, 0.44 mmol), TMEDA (0.07 mL, 0.46 mmol) and Cl3CCCl3 (1.0 M, 0.57 mL, 0.57 mmol) at −78
°C, and warmed to rt over 16 h. Normal workup, followed by flash column chromatography (EtOAc:PE 1:2)
afforded a mixture of 8d and 9d as an offꢀwhite solid (138 mg, 96%, 59:41), mp 184.5−185.5 °C (EtOAc);
1H NMR (300 MHz, CDCl3) δ 8.77−8.62 (m, 2H – 8d, 3H – 9d), 8.58 (d, J = 9.3 Hz, 1H – 9d), 8.49 (d, J =
9.3 Hz, 1H – 8d), 8.40 (d, J = 9.6 Hz, 1H – 9d), 7.96−7.94 (m, 2H – 8d, 2H – 9d), 7.86 (d, J = 9.0 Hz, 1H –
8d), 7.81 (s, 1H – 8d), 7.72−7.59 (m, 2H – 8d, 2H – 9d), 7.55 (d, J = 9.1 Hz, 1H – 9d), 3.60−3.53 (m, 2H –
8d, 2H – 9d), 3.45 (q, J = 6.9 Hz, 2H – 8d, 2H – 9d), 1.38−1.34 (m, 3H – 8d, 3H – 9d), 1.28−1.26 (m, 3H
– 8d, 3H – 9d); 13C NMR (75 MHz, CDCl3) δ 153.4 (2C), 145.9, 145.6, 132.1, 132.07, 131.4, 130.3,
130.27, 130.2, 129.2, 128.8, 128.5, 128.49, 128.2, 127.9, 127.89, 127.8, 127.6, 127.1, 126.9, 126.8,
126.6, 126.55, 126.3, 124.7, 123.1, 123.0, 122.9, 122.8, 122.6, 122.5, 122.1, 122.0, 121.0, 120.8, 120.2,
42.5 (2C), 42.1 (2C), 14.2 (2C), 13.3 (2C); FTIR (KBr, cmꢀ1) 2978, 2934, 1731, 1472, 1419, 1381, 1274,
751; HRMS (ESI) m/z [M + Na]+ for formula C23H20ClNNaO2: calcd, 400.1080; found 400.1090.
3-Methylchrysen-2-yl N,N-diethyl-O-carbamate (8e) and 1-Methylchrysen-2-yl N,N-diethyl-O-carbamate
(9e). According to the general procedure, 2b (104 mg, 0.30 mmol) in THF (2.2 mL) was treated with sꢀ
BuLi (0.54 mL, 0.61 mmol), TMEDA (0.09 mL, 0.61 mmol) and MeI (0.06 mL, 0.91 mmol) at −95 °C, and
warmed to rt over 4 h. Normal workup, followed by flash column chromatography (EtOAc:PE 1:8), the title
compounds were isolated as a mixture 8e and 9e (85 mg, 79%, 54:46) as an offꢀwhite solid, mp
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193.0−194.5 °C (EtOAc); H NMR: (400 MHz, CDCl3) δ 8.77−8.71 (m, 1H – 8e, 2H – 9e), 8.68−8.63 (m,
2H – 8e, 2H – 9e), 8.59 (s, 1H−8e), 7.99−7.96 (m, 2H – 8e, 2H – 9e ), 7.92 (d, J = 9.1 Hz, 1H – 8e), 7.73
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(s, 1H – 8e), 7.72−7.68 (m, 1H – 8e, 1H – 9e), 7.66−7.61 (m, 1H – 8e, 1H – 9e), 3.59−3.56 (m, 2H – 8e,
2H – 9e), 3.49−3.47 (m, 2H – 8e, 2H – 9e), 2.54 (s, 3H – 8e), 2.65 (s, 3H – 9e), 1.38−1.35 (m, 3H – 8e,
3H – 9e), 1.30−1.27 (m, 3H – 8e, 3H – 9e); 13C NMR (100 MHz, CDCl3) δ 154.2, 154.0, 149.1, 147.6,
132.1, 131.9, 131.87, 131.5, 130.5, 130.4, 130.3, 128.5, 128.4, 128.3, 128.27, 127.8, 127.6, 127.4, 127.3,
127.1, 126.7, 126.6, 126.5, 126.2, 126.1, 125.5, 125.1, 123.1, 123.0, 122.9,122.0, 121.9, 121.5, 121.4,
121.2, 120.9, 119.9, 42.3 (2C), 41.9 (2C), 17.4, 14.4, 14.3, 13.4 (2C), 12.0; FTIR (KBr, cmꢀ1) 2976, 1720,
1420, 1273, 1246; HRMS (ESI) m/z [M + H]+ for formula C24H24O2N : calcd, 358.1807; found, 358.1805.
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3-(N,N-Diethylcarbamoyl)chrysen-2-yl
N,N-diethyl-O-carbamate
(8f)
and
1-(N,N-
Diethylcarbamoyl)chrysen-2-yl N,N-diethyl-O-carbamate (9f). According to the general procedure, 2b (107
mg, 0.31 mmol) in THF (2.2 mL) was treated with sꢀBuLi (0.55 mL, 0.62 mmol), TMEDA (0.09 mL, 0.62
mmol) and Et2NCOCl (0.12 mL, 0.93 mmol) at −95 °C, and warmed to rt over 4 h. By normal workup,
followed by flash column chromatography (EtOAc:PE 1:2), a mixture of compounds 8f and 9f were
isolated as a beige solid (96 mg, 70%, 75:25), mp 181.5−182.5 °C (EtOAc); 1H NMR: (400 MHz, CDCl3) δ
8.78−8.73 (m, 2H – 9f), 8.71 (d, J = 8.2 Hz, 1H – 8f), 8.70 (d, J = 9.1 Hz, 1H – 8f), 8.67 (s, 1H – 8f, 8.63
(d, J = 9.2 Hz, 1H – 9f), 8.59 (d, J = 9.1 Hz, 1H – 8f), 7.99−7.91 (m, 3H – 8f, 2H – 9f), 7.89 (s, 1H−8f),
7.69−7.59 (m, 2H – 8f, 2H – 9f), 3.83−3.07 (m, 8H – 8f, 8H – 9f), 1.39 (t, J = 7.1 Hz, 3H – 9f), 1.33ꢀ1.25
(m, 6H – 8f, 3H – 9f), 1.22 (t, J = 7.1 Hz, 3H – 8f, 3H – 9f), 1.11 (t, J = 7.1 Hz, 3Hꢀ 8f), 0.94 (t, J = 7.1 Hz,
3H – 9f); 13C NMR (100 MHz, CDCl3) δ 167.9, 166.6, 153.5, 153.4, 145.7, 145.3, 132.8, 131.9, 130.3,
130.2, 130.1, 129.2, 128.4, 128.0, 127.9, 127.8, 127.75, 127.7, 127.5, 126.7, 126.6, 126.4, 126.37, 124.4,
123.4, 122.9, 122.86, 122.6, 122.4, 122.3, 121.8, 120.94, 120.91, 120.7, 42.9, 42.87, 42.2, 42.0, 38.9,
38.7, 14.1, 13.9, 13.8, 13.3, 12.9, 12.7; FTIR (KBr, cmꢀ1) 2971, 2932, 1714, 1637, 1474, 1420, 1271,
1246; HRMS (ESI) m/z [M+Na]+ for formula C28H30O3N2Na: calcd, 465.2154; found, 465.2141.
3-(Hydroxy)chrysene-2-carbaldehyde (8g) and 1-(Hydroxy)chrysene-2-carbaldehyde (9g). According to
the general procedure, 2b (103 mg, 0.30 mmol) in THF (2.2 mL) was treated with sꢀBuLi (0.53 mL, 0.60
mmol), TMEDA (0.09 mL, 0.60 mmol) and DMF (0.07 mL, 0.90 mmol) at −95 °C, and warmed to rt over
3.5 hours. Normal workup, followed by flash column chromatography (EtOAc:PE 1:8) afforded a mixture of
compound 8g and 9g as a yellow solid (53 mg, 64%, 68:32), mp 221.1−222.1 °C (Acetone); 1H NMR: (400
MHz, CDCl3) δ 13.02 (s, 1H – 9g), 10.99 (s, 1H – 9g), 10.62 (s, 1H – 8g), 10.22 (s, 1H – 8g), 8.97 (s, 1H –
8g), 8.96 (d, J = 9.6 Hz, 1H – 9g), 8.88 (d, J = 9.6 Hz, 1H – 9g), 8.78 (d, J = 9.3 Hz, 1H – 8g), 8.75 (d, J =
8.4 Hz, 1H – 9g), 8.72 (d, J = 8.4 Hz, 1H – 8g), 8.62 (d, J = 9.0 Hz, 1H – 8g), 8.57 (d, J = 9.0 Hz, 2H –
9g), 8.06 (d, J = 8.9 Hz, 1H – 8g), 8.04−7.99 (m, 2H – 9g), 8.00 (app d, J = 9.4 Hz, 1H – 8g), 7.86 (d, J =
9.1 Hz, 1H – 8g), 7.76−7.72 (m, 1H – 9g), 7.75−7.71 (m, 1H – 8g), 7.68−7.64 (m, 1H – 9g), 7.67−7.63 (m,
1H – 8g), 7.44 (s, 1H – 8g), 7.34 (d, J = 9.3 Hz, H – 9g); 13C NMR: (100 MHz, CDCl3) δ 196.8, 193.9,
157.2, 138.0, 133.8, 132.2, 131.9, 130.4, 128.8, 128.7 (2C), 128.6,128.5, 127.2, 126.9, 126.5, 126.0,
125.9, 124.7, 124.2, 122.8, 121.5, 120.5, 120.3, 118.8, 117.8, 113.5; FTIR (KBr, cmꢀ1) 2924, 1723, 1660,
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1,3-bis(Trimethylsilyl)chrysen-2-yl diethylcarbamate (10). According to the general procedure, 2b (71 mg,
0.21 mmol) in THF (2.0 mL) was treated with sꢀBuLi (0.46 mL, 0.53 mmol), TMEDA (0.03 mL, 0.41 mmol)
and TMSCl (0.05 mL, 0.41 mmol) at −78 °C for 12 h. Normal workup, followed by flash column
chromatography (EtOAc:PE 1:4) afforded product 10 (99 mg, 98%) as a colorless solid, mp. 166.4−167.1
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°C (EtOAc); H NMR (400 MHz, CDCl3) δ 9.05 (s, 1H), 8.80−8.74 (m, 3H), 8.42 (d, J = 9.5 Hz, 1H),
8.03−8.00 (m, 2H), 7.74−7.70 (m, 1H), 7.67−7.63 (m, 1H), 3.79−3.62 (m, 2H), 3.49−3.43 (m, 2H), 1.36 (t,
J = 7.1 Hz, 3H), 1.27 (t, J = 7.1 Hz, 3H), 0.60 (s, 9H), 0.50 (s, 9H); 13C NMR (100 MHz, CDCl3) δ 159.1,
154.9, 138.0, 133.2, 132.0, 131.9, 130.4, 129.1, 128.9, 128.4, 127.9, 127.4, 127.3, 127.1, 126.6, 126.2,
123.0, 121.2, 121.18, 40.9, 40.7, 13.5, 12.8, 2.4, ꢀ0.4; FTIR (KBr, cmꢀ1) 2976, 2955, 2898, 1707, 1472,
1422, 1379, 1343, 1279, 1236; HRMS (ESI) m/z [M + Na]+ for formula C29H37NNaO2Si2: calcd, 510.2261;
found 510.2255.
2-(Trimethysilyl)chrysene-3-yl N,N-diethyl-O-carbamate (11a). According to the general procedure, 2c
(134 mg, 0.39 mmol) in THF (2.5 mL) was treated with sꢀBuLi (0.37 mL, 0.43 mmol), TMEDA (0.07 mL,
0.46 mmol) and TMSCl (0.07 mL, 0.55 mmol) at −78 °C for 1.5 h. Normal workup, followed by flash
column chromatography (EtOAc:PE 1:4) afforded product 11a (144 mg, 89%) as an offꢀwhite solid, mp.
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106.0−107.0 °C (EtOAc); H NMR (300 MHz, CDCl3) δ 8.78 (d, J = 8.2 Hz, 1H), 8.66 (t, J = 8.8 Hz, 2H),
8.41 (s, 1H), 8.12 (s, 1H), 8.02−7.97 (m, 3H), 7.73−7.64 (m, 2H), 3.62 (q, J = 7.1 Hz, 2H), 3.51 (q, J = 7.0
Hz, 2H), 1.38 (t, J = 7.2 Hz, 3H), 1.29 (t, J = 7.2 Hz, 3H), 0.44 (s, 9H); 13C NMR (75 MHz, CDCl3) δ 154.6,
154.5, 136.3, 132.3, 132.29, 131.9, 130.4, 129.4, 128.5, 128.49, 127.7, 127.0, 126.9, 126.5, 126.4, 123.2,
121.6, 120.5, 115.5, 41.9, 41.6, 14.3, 13.3, ꢀ0.8; FTIR (KBr, cmꢀ1) 2961, 1699, 1467, 1420, 1310, 1271;
HRMS (ESI) m/z [M+Na]+ for formula C26H29NNaO2Si: calcd, 438.1865; found 438.1858.
2-Iodochrysen-3-yl N,N-diethyl-O-carbamate (11b). According to the general procedure, 2c (117 mg, 0.34
mmol) in THF (5 mL) was treated with sꢀBuLi (0.36 mL, 0.40mmol), TMEDA (0.06 mL, 0.40 mmol) and
Iodine in THF (0.5 M, 1.0 mL, 0.5 mmol) at −78 °C, and warmed to rt over 18 h. Normal workup, followed
by flash column chromatography (EtOAc:PE 1:2) afforded product 11b (145 mg, 91%) as a beige solid,
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mp. 200.5−201.5 °C (EtOAc); H NMR (400 MHz, CDCl3) δ 8.69 (d, J = 8.2 Hz, 1H), 8.60 (d, J = 9.1 Hz,
1H), 8.52 (d, J = 8.8 Hz, 1H), 8.51 (s, 1H), 8.41 (s, 1H), 7.97−7.93 (m, 2H), 7.79 (d, J = 8.0 Hz, 1H),
7.71−7.67 (m, 1H), 7.65−7.61 (m, 1H), 3.65 (q, J = 7.1 Hz, 2H), 3.50 (q, J = 7.1 Hz, 2H), 1.43 (t, J = 7.1
Hz, 3H), 1.31 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 153.4, 149.4, 139.0, 132.3, 131.3, 131.2,
130.2, 128.5, 128.4, 127.6, 127.4, 126.7, 126.6, 125.5, 123.1, 121.6, 121.0, 116.7, 90.1, 42.4, 42.1, 14.4,
13.4; FTIR (KBr, cmꢀ1) 2973, 1723, 1469, 1417, 1380, 1318, 1275; HRMS (ESI) m/z [M+Na]+ for formula
C23H20INNaO2: calcd, 492.0436; found 492.0428.
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2-Bromochrysen-3-yl N,N-diethyl-O-carbamate (11c). According to the general procedure, 2c (100 mg,
0.29 mmol) in THF (2.2 mL) was treated with sꢀBuLi (0.28 mL, 0.32 mmol), TMEDA (0.05 mL, 0.32 mmol)
and Br2 (0.02 mL, 0.44 mmol) at −78 °C for 16 h. Normal workup, followed by flash column
chromatography (EtOAc:PE 1:4) afforded product 11c (69.7 mg, 57%) as a beige solid, mp. 117.0−118.0
°C (EtOAc); 1H NMR (400 MHz, CDCl3) δ 8.71 (d, J = 8.5 Hz, 1H), 8.63 (d, J = 9.3 Hz, 1H), 8.56 (s, 1H),
8.53 (d, J = 9.2 Hz, 1H), 8.19 (s, 1H), 7.97 (dd, J = 1.2 Hz, 7.8 Hz, 1H), 7.96 (d, J = 9.0 Hz, 1H), 7.83 (d, J
= 9.1 Hz, 1H), 7.71−7.67 (m, 1H), 7.66−7.62 (m, 1H), 3.63 (q, J = 7.1 Hz, 2H), 3.49 (q, J = 7.1 Hz, 2H),
1.41 (t, J = 7.1 Hz, 3H), 1.30 (t, J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 153.4, 146.9, 132.4, 132.3,
130.8, 130.4, 128.5, 128.3, 127.6, 127.5, 126.8, 126.6, 125.6, 123.1, 121.8, 121.1,117.1, 115.9, 42.4,
42.1, 14.3, 13.3; FTIR (KBr, cmꢀ1) 2972, 1722, 1470, 1417, 1380, 1318, 1274, 747; HRMS (ESI) m/z [M +
H]+ for formula C23H2281BrNNaO2: calcd, 446.0732; found 446.0548.
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2-Chlorochrysen-3-yl N,N-diethyl-O-carbamate (11d). According to the general procedure, 2c (102 mg,
0.30 mmol) in THF (2.2 mL) was treated with sꢀBuLi (0.30 mL, 0.33 mmol), TMEDA (0.05 mL, 0.33 mmol)
and Cl3CCCl3 (106 mg, 0.45 mmol) in THF (1 mL) at −78 °C, and warmed to rt over 9 h. Normal workup,
followed by flash column chromatography (EtOAc:hexane 1:9) afforded product 11d as an orange solid
(78 mg, 70%), mp. 184.5−185.5 °C (EtOAc); 1H NMR (400 MHz, CDCl3) δ 8.66 (d, J = 8.4 Hz, 1H),8.58 (d,
J = 9.1 Hz, 1H), 8.54 (s, 1H), 8.48 (d, J = 9.1 Hz, 1H), 7.98 (s, 1H), 7.96−7.91 (m, 2H), 7.78 (d, J = 9.1 Hz,
1H), 7.69−7.61 (m, 2H), 3.61 (q, J = 7.0 Hz, 2H), 3.50 (q, J = 6.9 Hz, 2H), 1.41 (t, J = 7.1 Hz, 3H), 1.31 (t,
J = 7.1 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 153.5, 146.0, 132.2, 130.4, 130.3, 129.8, 129.0, 128.5,
128.3, 127.53, 127.52, 126.8, 126.6, 126.5, 125.7, 123.1, 121.8, 121.1, 117.8, 42.5, 42.1, 14.2, 13.3; FTIR
(KBr, cmꢀ1) 2975, 2936, 1724, 1471, 1419, 1381, 1318, 1276, 747; HRMS (ESI) m/z [M + Na]+ for formula
C23H20ClNNaO2: calcd, 400.1080; found 400.1078.
2-Methylchrysen-3-yl N,N-diethyl-O-carbamate (11e). According to the general procedure, 2c (100 mg,
0.29 mmol) in THF (2.2 mL) was treated with sꢀBuLi (0.52 mL, 0.58 mmol), TMEDA (0.09 mL, 0.58 mmol)
and MeI (0.05 mL, 0.87 mmol) at −95 °C, and warmed to rt over 4 h. Normal workup, followed by flash
column chromatography (EtOAc:PE 1:8), afforded compound 11e as pale yellow solid (100 mg, 96%), mp.
166.2−167.0 °C (EtOAc); 1H NMR (400 MHz, CDCl3) δ 8.75 (d, J = 8.3 Hz, 1H), 8.62 (d, J = 9.5 Hz, 2H),
8.47 (s, 1H), 8.00−7.96 (m, 2H), 7.90 (d, J = 9.0 Hz, 1H), 7.80 (s, 1H), 7.72−7.68 (m, 1H), 7.65−7.61 (m,
1H), 3.59 (q, J = 6.8 Hz, 2H), 3.50 (q, J = 7.0 Hz, 2H), 2.48 (s, 3H), 1.39 (t, J = 7.7 Hz, 3H), 1.30 (t, J = 6.9
Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 154.1, 149.4, 132.0, 130.5, 130.3, 130.1, 130.0, 129.8, 128.4,
127.8, 127.0, 126.5, 126.4, 126.1, 123.0, 121.4, 120.6, 115.6, 42.3, 41.9, 16.7, 14.3, 13.4; FTIR (KBr, cmꢀ
1) 2972, 1718, 1473, 1420, 1275, 1260; HRMS (ESI) m/z [M+H]+ for formula C24H24O2N : calcd, 358.1807;
found, 358.1803.
2-(N,N-Diethyl carbamoyl)chrysen-3-yl N,N-diethyl-O-carbamate (11f). According to the general
procedure, 2c (102 mg, 0.30 mmol) in THF (2.2 mL) was treated with sꢀBuLi (0.53 mL, 0.59 mmol),
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TMEDA (0.09 mL, 0.59 mmol) and Et2NCOCl (0.11 mL, 0.89 mmol) at −95 °C, and warmed to rt over 4 h.
Normal workup, followed by flash column chromatography (EtOAc:PE 1:2), afforded compound 11f as
colorless solid (116 mg, 88%), mp. 180.2−181.2 °C (EtOAc); 1H NMR (400 MHz, CDCl3) δ 8.72 (d, J = 8.3
Hz, 1H), 8.65 (d, J = 9.1 Hz, 1H), 8.61 (s, 1H), 8.58 (d, J = 9.1 Hz, 1H), 7.97−7.92 (m, 2H), 7.89 (s, 1H),
7.70−7.65 (m, 1H), 7.64−7.60 (m, 1H), 3.92−3.13 (br m, 8H), 1.33−1.26 (m, 6H), 1.23 (t, J = 7.0 Hz, 3H),
1.10 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 167.5, 153.7, 146.1, 132.2, 131.3, 130.2, 130.1,
129.1, 128.5, 128.4, 127.5, 127.3, 126.6, 126.54, 126.51, 123.1, 121.3, 116.7, 42.9, 42.2, 42.0, 38.8, 14.1,
13.8, 13.3, 12.6; FTIR (KBr, cmꢀ1) 2978, 2933, 1719, 1630, 1472, 1420, 1382, 1347, 1317, 1295, 1272;
HRMS (ESI) m/z [M+Na]+ for formula C28H30O3N2Na: calcd, 465.2154; found, 465.2149
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2-(Hydroxy)chrysene-3-carbaldehyde (11g). According to the general procedure, 2c (1.08 g, 3.15 mmol) in
THF (20 mL) was treated with sꢀBuLi (7.05 mL, 6.30 mmol), TMEDA (0.94 mL, 6.30 mmol) and DMF (0.73
mL, 9.44 mmol) at −95 °C, and warmed to rt over 3.5 h. Normal workup, followed by flash column
chromatography (EtOAc:PE 1:8), afforded compound 11g as yellow solid (1.23 g, 72%), mp. 230.5−231 5
°C (Acetone); 1H NMR (400 MHz, CDCl3) δ 10.61 (s, 1H), 10.13 (s, 1H), 8.74 (d, J = 8.1 Hz, 1H), 8.56 (t, J
= 8.0 Hz, 2H), 8.20 (s, 2H), 8.00 (d, J = 8.6 Hz, 1H), 7.95 (d, J = 9.1 Hz, 1H), 7.72−7.68 (m, 2H); 13C NMR
(100 MHz, CDCl3) δ 196.4, 157.5, 136.8, 133.0, 130.8, 130.2, 128.7, 127.7, 127.4, 127.3, 127.0, 126.8,
125.8, 123.5, 121.6, 121.4, 119.9,109.2; FTIR (KBr, cmꢀ1) 3460, 1666, 1634, 1435, 1384, 1343; HRMS
(ESI) m/z [M ꢀ H]ꢀ for formula C19H11O2: calcd, 271.0759; found, 271.0764.
N,N-Diethyl-5-hydroxychrysene-6-carboxamide (12). According to the general procedure, 2e (198 mg,
0.58 mmol) was treated with a precooled mixture of sꢀBuLi (0.1 mL, 0.67 mmol) and TMEDA (0.57 mL,
0.67 mmol) in THF (2.4 mL) at ꢀ98 °C. The mixture was warmed to rt overnight (17 h) and normal workꢀup
procedures, followed by flash column chromatography (EtOAc:hexane 1:6) afforded orthoꢀFries product
1
12 (156 mg, 79%) as beige solid, mp. 187.6−188.9 °C (Acetone); H NMR (400 MHz, CDCl3) δ 9.87 (s,
1H), 9.61 (d, J = 8.7 Hz, 1H), 8.31 (d, J = 9.2 Hz, 1H), 7.85−7.83 (m, 2H), 7.62 (dd, J = 0.6, 8.2 Hz, 1H),
7.53−7.49 (m, 1H), 7.45−7.38 (m, 2H), 7.28−7.24 (m, 1H), 3.46 (br s, 4H), 1.19 (br s, 6H); 13C NMR (100
MHz, CDCl3) δ 170.6, 151.7, 132.6, 130.9, 130.6, 129.1, 129.0, 128.8, 127.8, 127.0, 126.4, 125.9, 125.8,
124.0, 123.2, 123.1, 121.4, 120.5, 116.3, 41.8, 13.5; FTIR (KBr, cmꢀ1) 3469, 1598, 1582, 1491, 1429,
1379, 1314, 1343, 1240, 1200, 1125; HRMS (ESI) m/z [M + H]+ for formula C23H22NO2: calcd, 344.1651;
found, 344.1652.
ASSOCIATED CONTENT
Supporting information
Supporting Information “This material is available free of charge via the Internet at http://pubs.acs.org.”
NMR spectra of the new compounds and HRMS of deuterium quench experiments (PDF)
AUTHOR INFORMATION
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Corresponding Author
*Eꢀmail: kare.b.jorgensen@uis.no
ORCID
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Sindhu Kancherla: 0000ꢀ0001ꢀ7592ꢀ1179
Marianne Lorentzen:
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Victor Snieckus: 0000ꢀ0002ꢀ6448ꢀ9832
Kåre B. Jørgensen: 0000ꢀ0003ꢀ0662ꢀ1839
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
We thank NSERC Canada for support of our DG (Discovery Grant) programs. We are grateful to Dr.
Bjarte Holmelid at the University of Bergen, Norway and Ing. Jostein A. Johansen at the University of
Tromsø, Norway for providing HRMS analysis of the compounds.
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