Functionalization of homodiamantane: Oxygen insertion reactions without rearrangement with dimethyldioxirane

Article abstract of DOI:10.1021/jo4026594

Homodiamantane bromination and nitroxylation are accompanied by contraction of the seven-membered ring to give the corresponding substituted 1-diamantylmethyl derivatives. In contrast, CH-bond hydroxylations with dimethyldioxirane retain the cage and give both apically and medially substituted homodiamantanes. The product ratios are in accord with the barriers for the oxygen insertion computed with density functional theory methods only if solvation is included through a polarizable continuum model. B3LYP-D3 and M06-2X computations with a 6-31G(d,p) basis set on the oligomeric van der Waals complexes predict the potential of homodiamantane derivatives for surface modifications with conformationally slightly flexible diamondoid homologues.

Full text of DOI:10.1021/jo4026594

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Note
Functionalization of Homodiamantane: Oxygen Insertion
Reactions without Rearrangement with Dimethyldioxirane
Andrey A Fokin, Tatyana S Zhuk, Alexander E Pashenko, Valeriy V
Osipov, Pavel A Gunchenko, Michael Serafin, and Peter Richard Schreiner
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/jo4026594 • Publication Date (Web): 16 Jan 2014
Downloaded from http://pubs.acs.org on January 17, 2014
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Functionalization of Homodiamantane: Oxygen Insertion Reactions without
Rearrangement with Dimethyldioxirane
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Andrey A. Fokin,*a,b Tatyana S. Zhuk,a Alexander E. Pashenko,a Valeriy V. Osipov,a Pavel A.
Gunchenko,a Michael Serafin,c and Peter R. Schreiner*b
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a Department of Organic Chemistry, Kiev Polytechnic Institute, pr. Pobedy 37, 03056 Kiev,
Ukraine, aaf@xtf.kpi.ua
b Institut für Organische Chemie der Justus-Liebig-Universität, Heinrich-Buff-Ring 58, D-
35392 Giessen, Germany, prs@uni–giessen.de
c Institut für Anorganische Chemie der Justus-Liebig-Universität, Heinrich-Buff-Ring 58, D-
35392 Giessen, Germany
RECEIVED DATE (will be automatically inserted after manuscript is accepted).
Abstract:
HO
O
O
N
E+N–
OH
+
Homodiamantane bromination and nitroxylation are accompanied by contraction of the sevenꢀ
membered ring to give the corresponding substituted 1ꢀdiamantylmethyl derivatives. In
contrast, CHꢀbond hydroxylations with dimethyldioxirane retain the cage and give both
apically and medially substituted homodiamantanes. The product ratios are in accord with the
barriers for the oxygen insertion computed with density functional theory methods only if
solvation is included through a polarizable continuum model. B3LYPꢀD3 and M06ꢀ2X
computations with a 6ꢀ31G(d,p) basis set on the oligomeric vanꢀderꢀWaals complexes predict
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the potential of homodiamantane derivatives for surface modifications with conformationally
slightly flexible diamondoid homologues.
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Diamondoids1 are defined as a group of nanometer–size saturated hydrocarbons whose
structures resemble part of the diamond lattice, i.e., these are hydrogen–terminated
nanodiamonds. Among many others, diamantane (1) and [121]tetramantane (2), Fig. 1) are
accessible in sizeable quantities from crude oil.2 The theoretically predicted3 ability of
diamondoidꢀbased materials to resemble the properties of diamond, in particular, its negative
electron affinity (NEA), was proven experimentally for self–assembled monolayers (SAMs)
of diamondoid thiols on Au and Ag surfaces.4 These new photocathode devices displays
monochromatic emission with up to 70% electron yield,5 which is far beyond the efficiency of
bulk hydrogen–capped diamond.4,6,7 Conformational flexibility is one of key factors that
determine SAM properties. Very recently it was shown that conformational disorder
enhances electron transfer through alkyl monolayers.8 Nearꢀedge Xꢀray absorption fine
structure spectroscopic9 and other measurements10 demonstrated that the selfꢀassembly of
thiols on gold surfaces occur in two steps whereby closer packing follows preliminary
aggregation, a process that may involve conformational changes that affect the density and the
electronic properties of SAMs.
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Figure 1. The structures of diamantane (1), [121]tetramantane (2), and homodiamantane (3)
with numbering of carbon atoms.
Homodiamantane (3, Fig. 1)11 is the simplest non–spherical diamondoid homologue
that displays modest conformational flexibility due to presence of a seven–membered ring
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similar to that of homadamantane.12 The interconversion of two degenerate C1ꢀminima
(bridge flip) occurs through the Csꢀsymmetric structure and is barrierless at various DFT
(B3LYP, B3LYPꢀD3, M06ꢀ2X, B3PW91) and ab initio (MP2) levels of theory. This makes 3
the first relevant candidate for testing the selfꢀassembly of moderately flexible homologated
diamondoids on surfaces.
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Diamondoid selfꢀassembly is effective due to intermolecular dispersion interactions
between the neighboring CHꢀterminated diamond–like surfaces.13 Recently, we have
experimentally confirmed that such type of bonding is responsible for strengthening the
central CC bonds in diamondoid dimers14 that are structurally related to graphane dimers.15,16
To predict the differences in the self–association of 3 vs. conformationally rigid parent 1 we
optimized the structures of their vanꢀderꢀWaals tetramers, in an attempt to model the
clustering of these hydrocarbons on surfaces. In order to account for the non–covalent
interactions we utilized the M06ꢀ2X functional17 that is parametrized to include medium
range electron correlation. For cleanꢀcut comparisons of the dispersion contributions we also
employed the a posteriori D3 dispersion corrections (B3LYPꢀD3).18 The B3LYPꢀD3/6ꢀ
31G(d,p) computed association energies of 1 and 3 to the tetramers A and B (Fig. 2) are 26.9
and 28.4 kcal mol–1, respectively. Even though the dimensions of these complexes are almost
identical (Fig. 2), the higher association energy for tetramer B is due to a larger number of
intermolecular CH contacts. Similar trends were are observed at M06ꢀ2X/6ꢀ31G(d,p) where,
although the absolute complexation energies are ca 10 kcal mol–1 lower than those at B3LYPꢀ
D3/6ꢀ31G(d,p), the tetramerization of 3 still is 2.1 kcal mol–1 more favorable than that of 1.
We envisage that the SAM morphologies are expected to be similar for 1 and 3, but the latter
hydrocarbon may form more densely packed and therefore likely also more stable
monolayers.
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Figure 2. The B3LYPꢀD3/6ꢀ31G(d,p) optimized vanꢀderꢀWaals tetramers of diamantane (A)
and homodiamantane (B) (selected interatomic distances in Å).
For the preparation of 3 we took the route through the homologation of diamantanone
(4)19 with NꢀmethylꢀNꢀnitrosoꢀpꢀtoluenesulfonamide. Further WolffꢀKishner reduction of
thus obtained mixture of homodiamoantanones gave 3 in 87% overall preparative yield
(Scheme 1).
Scheme 1. The preparation of homodiamantane (3).
In order to study the self–assembly properties of 3, surface attachment points must be
introduced into its structure; these are typically –OH, –SH, –COOH as well as other
nucleophilic functional groups. The presence of the six different types of tertiary C–H bonds
makes the selective functionalization of 3 rather challenging. As the functionalizations of
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diamondoids usually are most selective with electrophiles,20 we first tested the reactivity of 3
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towards bromine21 and 100% nitric acid,22 where the positively polarized bromine (Brn Brm
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– 24
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and nitronium nitrate (NO2 NO3 ) constituents achieve oxidative CH activations.
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Previously we successfully utilized these reagents for the functionalizations of diamantane,20
triamantane,25 [121],25 [123],26 [1(2)3]27 tetramantanes, Td–pentamantane,28 and
cyclohexamantane.27 As the selectivities of the functionalizations of diamondoids with
electrophiles correlate well with the stabilities of carbocations in the chosen positions of the
cage27,29ꢀ31 we first estimated the relative ꢀH298 of the tertiary carbocations derived from 3.
Again, we employed B3LYPꢀD3 and M06ꢀ2X, as the latter being particularly useful to
describe the highly delocalized charge in diamondoid cations.32 We found that the relative
stabilities of the tertiary carbocations derived from 3 vary substantially, whereby 3a with the
charge in the medial C12ꢀposition is the most favorable both at B3LYPꢀD3 and M06ꢀ2X with
a 6ꢀ31G(d,p) basis set (Fig. 3). This is due to the combination of two factors, namely i)
location of the carbocationic center in the seven–membered ring that reduces the strain and ii)
more effective delocalization of the charge within the cage as seen from the electrostatic
potential distributions (Fig. 3).
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Figure 3. The electrostatic potential surfaces and the relative stabilities of tertiary
homodiamantyl cations 3a–f (∆H298, kcal mol–1 at B3LYPꢀD3 (M06ꢀ2X)/6ꢀ31G(d,p)).
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The 4 kcal mol–1 energy gap between cations 3a and 3b (ca.) implies that the reaction
of 3 with electrophiles will be directed predominantly into the medial C12ꢀposition. We
found, however, that although bromination of 3 does occur at the computationally predicted
position, it is accompanied by ring contraction to furnish 1–bromomethyldiamantane (5) as
the main product (Scheme 2). The analogous rearrangement of parent homoadamantane in
the presence of bromine was documented earlier where it was suggested that contraction
occurs upon ionization of the halogenated product.33ꢀ36 As C–H brominations with neat
bromine occur through Hꢀcoupled electron transfer involving highly polarized transitions
structures23 leading to complexes of the respective carbocation with protonated bromine
(HBr2n+), the rearrangement of the homodiamantane cage may occur already at the CHꢀ
functionalization step. As it was shown that the transition structures for the reaction of cage
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hydrocarbons with HNO3 (modeled with an NO2 •••HNO3 complex)20 are early along the
reaction coordinate, i.e., less carbocation–like than those for the reaction with polarized
halogens,23 we hoped that the nitroxylation of 3 may retain the homoadamantane cage upon
CHꢀsubstitution.
Scheme 2. Yields of isolated products for the functionalizations of 3 with electrophiles.
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However, the reaction of 3 with 100% nitric acid, under conditions previously used for the
oxidations of a variety of cage hydrocarbons,27 followed by hydrolysis of the reaction
mixture, solely gave the rearranged product (1ꢀhydroxymethyldiamantane, 7).
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To prevent the potential rearrangement of the intermediate homodiamantane nitroxy
derivatives (if formed) we attempted quenching the reaction mixture with NaHCO3 and
reduction of the intermediate nitrate with H2/PtO2, but we still obtained the rearranged
products 7 and 8 (the Xꢀray crystal structure of 8 is shown in the SI). Decreasing the
nitroxylation temperature to –15 °C as well as nitroxylation of 3 in CF3COOH also resulted in
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rearrangement (Scheme 1).
We conclude that the preparation of medial tertiary
homodiamantane derivatives cannot be achieved with common electrophilic reagents. Even
though the attack of electrophiles occurs at the C12ꢀposition of 3, the intermediate cationic
intermediates contract and the homodiamantane cage cannot be retained.
We alternatively attempted the C(sp3)–H functionalizations utilizing reagents that
circumvent the formation of cationic intermediates. Dioxiranes37,38 were particularly
successful for the incorporation of hydroxyl functions into a number of cage compounds such
as adamantane,39 dehydroadamantanes,40 and diamantane20 with remarkable 3°/2°
selectivities, even when the cage is deactivated with electron–withdrawing groups. We
utilized dimethyldioxirane (DMD) that can readily be prepared from acetone and oxone
(KHSO5)2×KHSO4×K2SO4.41 The CHꢀfunctionalizations with DMD mechanistically are very
different from the reactions with other electrophiles and can be viewed as concerted
insertion40,42 or as radical abstraction followed by fast rebound.43 In any case carbocationic
transition structures or intermediates are not involved in such transformations. The computed
transition structures (Fig. 4) for the reaction of DMD with 3 at M06ꢀ2X/6ꢀ31G(d,p) and
B3LYPꢀD3/6ꢀ31G(d,p) show that the attack of the reagent on the C12–H position of 3 through
TS1 dominates and the functionalization is expected to proceed with the same positional
selectivity as found above. As TS3 is substantially higher in energy than the medial transition
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structures TS2 and TS4, the formation of apical derivatives is not expected based on the gas
phase computations. The fact that the most sterically hindered position is attacked
preferentially (TS1) demonstrates the dominance of electronic43 over steric44,45 factors in the
reaction of 3 with DMD. The transition structures are highly polarized and their relative
energies nicely mirror the stabilities of the respective carbocations (Fig. 3).
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Figure 4. The M06ꢀ2X/6ꢀ31G(d,p) (black), PCM(CH2Cl2)ꢀM06ꢀ2X/6ꢀ31G(d,p) (blue),
B3LYPꢀD3/6ꢀ31G(d,p) (green), and PCM(CH2Cl2)ꢀB3LYPꢀD3/6ꢀ31G(d,p) (light brown)
relative barriers for the CHꢀinsertions to 3 with dimethyldioxirane (∆H298, kcal mol–1).
As we found that accounting for solvent effects in the CH–bond activations with
uncharged electrophiles such as diacetyl changes the positional selectivities,46 we utilized the
polarizable continuum model (PCM) in our computations with DMD in dichloromethane (ε=
8.93) as a model solvent. While the differences in the barriers for the Hꢀinsertions into the
C2ꢀ and other positions of 3 are sizable (2.2 kcal mol–1 at B3LYP), accounting for the solvent
effects changes this picture considerably (Fig. 4): transition structures (TS1–TS3) become
close in energy (within 1 kcal mol–1) implying that the reaction of 3 with DMD will be
directed not only to the medial C2 and C12 but also to the apical C9–position. This is due to
generally higher polarizabilities of the apical transition structures46 and in accord with
previous solvent effect studies47 that demonstrated extraordinary high polarization of the
transition structures for reactions with dioxiranes. Although the barriers for the oxygen
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insertion vary only slightly, the formation of substantial amounts of apical product through
TS3 is expected based on the PCM–DFT computations.
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The reaction of 3 with in situ generated DMD gave a mixture of alcohols from which
the main products, homodiamantanꢀ9ꢀol (9) and homodiamantanꢀ12ꢀol (10), were isolated and
characterized individually in good preparative yields (Fig. 5); the product distribution is in
accord with our computations. The structure of 10 was confirmed by Xꢀray crystal structure
analysis. We were able to perform functional group exchange without rearrangement of the
cage, e.g., the reaction of 9 with SOBr2 gave 9ꢀbromohomodiamantane (12), whose structure
was also confirmed by Xꢀray crystal structure data analysis (Fig. 5). The structures of 9, 10
and 12 were fully characterized through the NMR data (see SI for details).
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Figure 5. Preparative yields of the products for the reaction of homodiamantane (3) with
dimethyldioxirane and the Xꢀray crystal structures of homodiamantanꢀ12ꢀol (10) and 9ꢀ
bromohomodiamantane (12).
We conclude that the functionalizations of 3 with commonly employed electrophiles (Br2
and HNO3) inevitably are accompanied by ring contraction and formation of the
corresponding medial 1ꢀdiamantylmethyl derivatives. The situation with DMD is clearly
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different and 3 can be oxidized with DMD without cage rearrangement. The apical alcohol 9
and medial alcohol 10 that result from highꢀyielding oxygen insertion into the tertiary CH–
bonds of the seven–membered ring are easily separable. Such product distributions are in
accord with computed hydrogen abstraction barriers only if solvent effects are accounted for
in the computations. Hence, DMD, in contrast to the reaction with other electrophiles, allows
the preparation of both apical and medial derivatives of homodiamantane. These are valuable
building blocks for surface modifications with moderately conformationally flexible
diamondoid analogs.
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Experimental Section
General Information. NMR spectra were recorded at 400 and 600 MHz (1H)
spectrometers with TMS as internal standard. Highꢀresolution mass spectra (HRMS) were
recorded using electron impact ionization on a focusing sectorꢀtype mass spectrometer.
Products were purified by chromatography on 100−160 mesh silica gel. All melting points
were determined without correction. Commercially available reagents and solvents were used
without further purification.
Homodiamantane (3). A solution of KOH (5.4 g, 96 mmol) in a mixture of 10.2 mL
CH3OH and 10.2 mL of water was added dropwise to a wellꢀstirred solution of 3.1 g (15
19
mmol) of diamantanone (4)
and 16.4 g (76 mmol) of NꢀmethylꢀNꢀnitrosoꢀpꢀ
toluenesulfonamide in 64.2 mL of CH3OH at 0–3 °С and the reaction mixture was stirred for
10 h at rt. The reaction mixture was extracted with CHCl3 (5×15 mL), the combined extracts
were washed with water and brine, dried over Na2SO4 and solvent was evaporated. The
residual mixture of the isomeric homodiamantanones (3.2 g) and 1.6 mL of hydrazine hydrate
(N2H4⋅H2O) was heated in 30 mL of diethylene glycol for 2 h at 140 °C. The reaction mixture
was cooled and 3.58 g of KOH was added, water was evaporated and then the reaction
mixture was heated for 3 h at 180 °C, cooled, extracted with hexane (5×15 mL), the combined
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extracts were washed with water, dried over Na2SO4 and evaporated. The residue was purified
by column chromatography on silica gel (pentane) to give homodiamantane 3 (2.7 g, 13
mmol, 87%), which was identical to the material described previously.11
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Bromination of homodiamantane (3) with neat Br2. A mixture of 0.2 g of
homodiamantane 3 and 1.4 mL of neat bromine (distilled) was stirred for 15 min at rt,
quenched with NaHSO3 solution and extracted with CHCl3 (4 х 10 mL). The combined
extracts were washed with water, brine, and were dried over Na2SO4. Evaporation gave 0.5 g
of a mixture of monobromide 5 and dibromides. Purification by column chromatography
(hexane/ether 95/5) gave 0.153 g (55%) of 5 as a colorless solid. Mp = 117–118 oC. 1H NMR
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(400 MHz, CDCl3): 3.53 (s, 2 H), 2.05–1.39 (m, 19 H). C NMR: 45.9 (СН2), 41.6 (СН2),
38.7 (СН), 38.6 (СН2), 38.3 (СН), 37.8 (СН2), 37.5 (СН), 37.1 (С), 32.6 (СН2), 27.4 (СН),
25.6 (СН). MS (m/z): 201 (100%), 145 (10%), 131 (12%), 117 (15%), 105 (19%), 91 (25%).
Anal. calcd. for C15H21Br: C 64.06, H 7.53; found: C 64.18, H 7.63.
Bromination of homodiamantane (3) with Br2 in CCl4. A mixture of 0.2 g of 3 and
0.5 mL of neat bromine (distilled) was stirred in 4 mL of CCl4 for 40 min at rt, quenched with
NaHSO3 solution and extracted with CHCl3 (4 х 15 mL). The combined extracts were
washed with water, brine and were dried over Na2SO4. Purification by column
chromatography (hexane/ether 95/5) gave 0.116 g (42%) of monobromide 5 as a colorless
solid, whose spectral properties were identical to those described above.
Oxidation of homodiamantane (3) with HNO3 in CH2Cl2. A mixture of 0.2 g of 3,
CH2Cl2 (5 mL) and 1 mL of HNO3 (100%) was mixed at 0 oC, stirred for 20 min at 0 oC and
then 40 min at rt, and then diluted with water (5 mL). CH2Cl2 was then evaporated and the
reaction mixture was refluxed for 1.5 h. Then the reaction mixture was extracted with CHCl3
(5×10 mL), the combined extracts were washed with 10% Na2CO3 and water, dried over
Na2SO4. Column chromatography on silica gel (eluent of hexane/ethylacetate = 4/1) gave
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0.172 g (80%) 1–hydroxymethyl diamantane (7) as a colorless solid with H and C NMR
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spectra identical to literature data.48
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Oxidation of homodiamantane (3) with HNO3 in CF3COOH. A mixture of 0.2 g of
3 and 3 mL of HNO3 (65%) was stirred in 4.5 mL of CF3COOH for 2 h at 40 °С. The reaction
mixture was poured into 30 mL of water and extracted with CHCl3 (5×10 mL), the combined
extracts were washed with 10% Na2CO3 and water, dried over Na2SO4. GC/MS analysis of
the reaction mixture indicated a formation of diamantylmethyl trifluoroacetate 6 (85%), MS
(m/z): 314 (3%), 201 (8%), 187 (100%), 131 (13%), 117, 115 (14%), 91 (43%), 69 (35%).
Reaction mixture was diluted with 10% KOH ethanol solution and stirred at rt for 4 h. The
reaction mixture was poured into 50 mL of water and was extracted with CHCl3 (5×10 mL),
the combined extracts were washed with water, brine and dried over Na2SO4. Column
chromatography on silica gel (eluent of hexane/ethylacetate = 4/1) gave 0.180 g (85%) 1ꢀ
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hydroxymethyldiamantane (7) as a colorless solid with H and C NMR spectra identical to
literature data.48
Oxidation of homodiamantane (3) with HNO3. A solution of 2 mL HNO3 (100%) in 5 mL
of CH2Cl2 was added dropwise to a mixture of 0.2 g of 3 and 5 mL of CH2Cl2 at 0 oC, stirred
10 min at 0 oC, then 10 mL of CH2Cl2 was added to a reaction mixture and excess of HNO3
was neutralized by addition of dry NaHCO3 in small portions. When gas evolution stopped
the solution was decanted from the solid. Then solid was washed twice with 5 mL portions of
CH2Cl2, the extracts were combined and the solvent evaporated giving 0.255 g of the crude
reaction mixture as a yellow oil. The reaction mixture was diluted with 20 mL of dry
methanol, 20 mg of PtO2 was added and the reaction mixture was stirred under the H2
atmosphere for 3 h. The reaction mixture was filtered under argon atmosphere and the filtrate
was evaporated in vacuo. Column chromatography of the residue on silica gel gave 0.155 g
(72%) 1ꢀhydroxymethyldiamantane (7) (eluent of hexane/ethylacetate = 4/1) as a colorless
1
solid with H and 13C NMR spectra identical to literature data48 and 0.045 g (10%) of 1ꢀ
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hydroxyꢀ6ꢀhydroxymethyldiamantane (8) (eluent hexane/ethylacetate = 1/1) as a colorless
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solid. Mp = 180–181 oC. 1H NMR (400 MHz, CDCl3): 3.51 (s, 2 H), 2.28 (d, 2 H), 2.01 (m, 3
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H), 1.82 (t, 1 H), 1.78 (s, 2 H), 1.66 (s, 2 H), 1.61 (s, 2 H), 1.55 (s, 2 H), 1.38 (d, 4 H). C
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NMR: 71.7 (C), 67.9 (C), 48.1 (СН2), 44.9 (СН), 41.1 (СН), 40.8 (СН2), 38.9 (СН), 33.2
(СН2), 31.5 (СН), 30.7 (СН2), 28.3 (СН2). MS (m/z): 234 (11%), 216 (5%), 203 (100%), 185
(54%), 143 (9%), 129 (16%), 117 (7%), 105 (9%), 95 (10%), 91 (18%) EI–HRMS (m/z):
found 234.1623, calcd for C15H22O2 234.1620.
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Oxidation of homodiamantane 3 with DMD. To a mixture of 0.75 g (3.7 mmol) of 3, 10.2
g of Na2CO3, 7.3 mL of СН2Сl2, 10.2 mL of acetone and 10.2 mL of distilled water a solution
of 10.3 g (33.5 mmol) oxone in 15 mL of distilled water added dropwise under intense stirring
at 0 oC over 1 h. The reaction mixture was stirred at rt for 3 hours, extracted with CHCl3
(5×10 mL), the combined extracts were washed with water and brine, dried over Na2SO4.
Solvent evaporation gave 0.72 g of a mixture of monohydroxy derivatives of
homodiamantane. Column chromatography on silica gel (eluent of pentane/diethyl ether =
1/1) gave 0.13 g (14%) of 12ꢀhomodiamantanol (10), 0.34 g (42%) of 9ꢀhomodiamantanol (9)
and 0.21 g of the mixture of 6ꢀhomodiamantanol and 1ꢀhomodiamantanol (24%).
1
9ꢀHomodiamantanol (9) Mp = 137–138ºС. H NMR (400 MHz, CDCl3): 1.92 (m, 1H),
1.90–1.84 (m, 8 H), 1.81 (m, 1 H), 1.80–1.76 (m, 6 H), 1.76–1.70 (m, 3 H), 1.68 (s, 2 H), 1.62
13
(s, 1 H). C NMR: 71.8 (С), 47.8 (СН), 44.5 (СН2), 42.8 (СН), 40.7 (СН), 40.0 (СН2), 38.6
(СН), 37.6 (СН2), 36.6 (СН2), 28.3 (СН), 27.0 (СН2). MS (m/z): 218 (80%), 200 (100%), 143
(10%), 109 (21%), 91 (47%). EIꢀHRMS (m/z): found 218.1668, calcd. for C15H22O 218.1671.
o
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12–Homodiamantanol (10) Mp = 154–155 C. H NMR (400 MHz, CDCl3): 2.42 (d, 2 Н),
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2.0–1.85 (m, 7 Н), 1.75–1.6 (m, 7 Н), 1.55–1.55 (m, 5 Н), 1.3 (s, 1 Н). C NMR: 76.1 (С),
45.3 (СН), 41.7 (СН2), 39.7 (СН2), 39.2 (СН), 38.7 (СН2), 36.8 (СН), 34.5 (СН2), 31.3
(СН2), 28.5 (СН), 25.5 (СН). MS (m/z): 218 (10%), 200 (100%), 143 (10%), 129 (17%), 109
(45%), 91 (23%). EIꢀHRMS (m/z): found 218.1669, calcd. for C15H22O 218.1671.
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Reaction of homodiamantan-9-ol (10) with SOBr2. A mixture of 50 mg (0.18 mmol) of
9–hydroxyhomodiamantane (9), 16 mg (0.2 mmol) of pyridine, 41 mg (0.2 mmol) of SOBr2
and 2 mL of CH2Cl2 was stirred at 0 ºC for 15 min. Then the temperature was increased to rt,
the reaction mixture was poured into a solution of 10 mL of CH2Cl2 and 10 mL of water,
extracted with CH2Cl2 (4 х 10 mL). The combined extracts were washed with water, brine and
were dried over Na2SO4. Evaporation gave 63 mg (98%) of 9–bromohomodiamantane (12) as
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a white solid Mp = 123–124 C (hexane). H NMR (400 MHz, CDCl3): 2.75 (dd, 2 H), 2.57
(dd, 2 H), 2.35 (m, 2 H), 1.92 (m, 1 H), 1.91–1.75 (m, 3 H), 1.75–1.60 (m, 9 H), 1.67–1.57 (m
13
2 H). C NMR: 72.9 (С), 51.4 (СН2), 47.4 (СН2), 44.5 (СН), 40.1 (СН2), 39.9 (СН), 39.8
(СН), 38.4 (СН2), 36.2 (СН), 31.2 (СН2), 26.8 (СН). Anal. calcd. for C15H21Br: C 64.06, H
7.53; found: C 64.21, H 7.34.
ACKNOWLEDGMENT This work was supported by the the Ukrainian Basic Research
Foundation, Ministry of Science and Education of Ukraine and the Department of Energy,
Office of Basic Energy Sciences, Division of Materials, Science and Engineering under
Contract DE–AC–76SF00515. We are grateful to Dipl.ꢀChem. Jonathan Becker (University
Giessen) for the interpretation of the Xꢀray crystal structure data of compound 10.
Supporting Information Available: The experimental and computational details, the copies
of NMR spectra, Xꢀray crystal structures, as well as xyzꢀcoordinates of optimized species are
available form www.pubs.acs.org.
References
(1) Decker, H. Angew. Chem. 1924, 37 795–822.
(2) Dahl, J. E.; Liu, S. G.; Carlson, R. M. K. Science 2003, 299, 96–99.
(3) Drummond, N. D.; Williamson, A. J.; Needs, R. J.; Galli, G. Phys. Rev. Lett. 2005, 95, 096801.
(4) Yang, W. L.; Fabbri, J. D.; Willey, T. M.; Lee, J. R. I.; Dahl, J. E.; Carlson, R. M. K.; Schreiner, P. R.; Fokin, A. A.;
Tkachenko, B. A.; Fokina, N. A.; Meevasana, W.; Mannella, N.; Tanaka, K.; Zhou, X. J.; van Buuren, T.; Kelly, M. A.;
Hussain, Z.; Melosh, N. A.; Shen, Z. X. Science 2007, 316, 1460–1462.
14
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Page 15 of 16
The Journal of Organic Chemistry
1
2
3
4
(5) Roth, S.; Leuenberger, D.; Osterwalder, J.; Dahl, J. E.; Carlson, R. M. K.; Tkachenko, B. A.; Fokin, A. A.; Schreiner, P.
R.; Hengsberger, M. Chem. Phys. Lett. 2010, 495, 102–108.
5
6
7
(6) van der Weide, J.; Zhang, Z.; Baumann, P. K.; Wensell, M. G.; Bernholc, J.; Nemanich, R. J. Phys. Rev. B 1994, 50,
5803–5806.
8
9
(7) Diederich, L.; Aebi, P.; Kuttel, O. M.; Schlapbach, L. Surf. Sci. 1999, 424, L314–L320.
(8) Ruther, R. E.; Cui, Q.; Hamers, R. J. J. Am. Chem. Soc. 2013, 135, 5751−5761.
(9) Hahner, G.; Woll, C.; Buck, M.; Grunze, M. Langmuir 1993, 9, 1955–1958.
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
(10) Bain, C. D.; Troughton, E. B.; Tao, Y. T.; Evall, J.; Whitesides, G. M.; Nuzzo, R. G. J. Am. Chem. Soc. 1989, 111,
321–335.
(11) Tabushi, I.; Aoyama, Y.; Takahash.N; Gund, T. M.; Schleyer, P. V. Tetrahedron Lett. 1973, 107ꢀ110.
(12) Liggero, S. H.; Schleyer, P. v. R.; Ramey, K. C. Spectrosc. Lett. 1969, 2, 197–201.
(13) Wang, Y.; Kioupakis, E.; Lu, X.; Wegner, D.; Yamachika, R.; Dahl, J. E.; Carlson, R. M. K.; Louie, S. G.; Crommie,
M. F. Nat. Mater. 2008, 7, 38–42.
(14) Fokin, A. A.; Chernish, L. V.; Gunchenko, P. A.; Tikhonchuk, E. Y.; Hausmann, H.; Serafin, M.; Dahl, J. E. P.;
Carlson, R. M. K.; Schreiner, P. R. J. Am. Chem. Soc. 2012, 134, 13641–13650.
(15) Fokin, A. A.; Gerbig, D.; Schreiner, P. R. J. Am. Chem. Soc. 2011, 133, 20036–20039.
(16) Janowski, T.; Pulay, P. J. Am. Chem. Soc. 2012, 134, 17520ꢀ17525.
(17) Zhao, Y.; Truhlar, D. G. Theor. Chem. Acc. 2008, 120, 215–241.
(18) Grimme, S.; Antony, J.; Ehrlich, S.; Krieg, H. J. Chem. Phys. 2010, 132, 154104.
(19) Courtney, T.; Johnston, D. E.; Rooney, J. J.; McKervey, M. A. J. Chem. Soc., Dalton Trans. 1 1972, 2691–2696.
(20) Fokin, A. A.; Tkachenko, B. A.; Gunchenko, P. A.; Gusev, D. V.; Schreiner, P. R. Chem. Eur. J. 2005, 11, 7091–7101.
(21) Landa, S.; Kriebel, S.; Knobloch, E. Chem. Listy 1954, 48, 61–64.
(22) Klimochkin, Y. N.; Abramov, O. V.; Moiseev, I. K.; Vologin, M. F.; Leonova, M. V.; Bagrii, E. I. Pet. Chem. 2000,
40, 415–418.
(23) Fokin, A. A.; Shubina, T. E.; Gunchenko, P. A.; Isaev, S. D.; Yurchenko, A. G.; Schreiner, P. R. J. Am. Chem. Soc.
2002, 124, 10718–10727.
(24) Klimochkin, Y. N.; Moiseev, I. K. Zh. Org. Khim. 1988, 24, 557ꢀ560.
(25) Schreiner, P. R.; Fokina, N. A.; Tkachenko, B. A.; Hausmann, H.; Serafin, M.; Dahl, J. E. P.; Liu, S. G.; Carlson, R.
M. K.; Fokin, A. A. J. Org. Chem. 2006, 71, 6709–6720.
(26) Schreiner, P. R.; Fokin, A. A.; Reisenauer, H. P.; Tkachenko, B. A.; Vass, E.; Olmstead, M. M.; Blaser, D.; Boese, R.;
Dahl, J. E. P.; Carlson, R. M. K. J. Am. Chem. Soc. 2009, 131, 11292–11293.
(27) Fokin, A. A.; Tkachenko, B. A.; Fokina, N. A.; Hausmann, H.; Serafin, M.; Dahl, J. E. P.; Carlson, R. M. K.;
Schreiner, P. R. Chem. Eur. J. 2009, 15, 3851–3862.
(28) Fokin, A. A.; Schreiner, P. R.; Fokina, N. A.; Tkachenko, B. A.; Hausmann, H.; Serafin, M.; Dahl, J. E. P.; Liu, S. G.;
Carlson, R. M. K. J. Org. Chem. 2006, 71, 8532–8540.
(29) Sosnowski, J. J.; Danaher, E. B.; Murray, R. K. J. Org. Chem. 1985, 50, 2759–2763.
(30) Karim, A.; McKervey, M. A. J. Chem. Soc., Dalton Trans. 1 1974, 2475–2479.
15
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Page 16 of 16
1
2
3
4
5
(31) Karim, A.; McKervey, M. A.; Engler, E. M.; Schleyer, P. v. R. Tetrahedron Lett. 1971, 3987–3990.
(32) Gunchenko, P. A.; Fokin, A. A. Theor. Exp. Chem. 2012, 47, 343–360.
6
7
(33) Israel, R. J.; Murray, R. K. J. Org. Chem. 1983, 48, 4701–4705.
8
(34) Stepanov, F. N. Vestn. Kiev. Politekhn. In-ta. Ser. Khim. Mashinostr. i Tekhnol. 1975, 12, 15–16.
9
(35) Yurchenko, A. G.; Stepanov, F. N.; Isaeva, S. S.; Zolotarev, B. M.; Kadentsev, V. I.; Chizhov, O. S. Org. Mass
Spectrom. 1970, 3, 1401–1410.
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
(36) Bingham, R. C.; Schleyer, P. v. R. J. Org. Chem. 1971, 36, 1198–1201.
(37) Mello, R.; Royo, J.; Andreu, C.; BaguenaꢀAno, M.; Asensio, G.; Elena GonzalezꢀNunez, M. Eur. J. Org. Chem. 2008,
455ꢀ466.
(38) GonzalezꢀNunez, M. E.; Royo, J.; Castellano, G.; Andreu, C.; Boix, C.; Mello, R.; Asensio, G. Org. Lett. 2000, 2, 831ꢀ
834.
(39) Mello, R.; Cassidei, L.; Fiorentino, M.; Fusco, C.; Curci, R. Tetrahedron Lett. 1990, 31, 3067–3070.
(40) Fokin, A. A.; Tkachenko, B. A.; Korshunov, O. I.; Gunchenko, P. A.; Schreiner, P. R. J. Am. Chem. Soc. 2001, 123,
11248–11252.
(41) Curci, R.; Fiorentino, M.; Troisi, L.; Edwards, J. O.; Pater, R. H. J. Org. Chem. 1980, 45, 4758ꢀ–4760.
(42) Annese, C.; D'Accolti, L.; Fusco, C.; Gandolfi, R.; Eaton, P. E.; Curci, R. Org. Lett. 2009, 11, 3574ꢀ3577.
(43) Zou, L. F.; Paton, R. S.; Eschenmoser, A.; Newhouse, T. R.; Baran, P. S.; Houk, K. N. J. Org. Chem. 2013, 78, 4037ꢀ
4048.
(44) Bovicelli, P.; Lupattelli, P.; Fiorini, V.; Mincione, E. Tetrahedron Lett. 1993, 34, 6103ꢀ6104.
(45) Cerre, C.; Hofmann, A. F.; Schteingart, C. D.; Jia, W. P.; Maltby, D. Tetrahedron 1997, 53, 435–446.
(46) Fokin, A. A.; Gunchenko, P. A.; Novikovsky, A. A.; Shubina, T. E.; Chernyaev, B. V.; Dahl, J. E. P.; Carlson, R. M.
K.; Yurchenko, A. G.; Schreiner, P. R. Eur. J. Org. Chem. 2009, 5153–5161.
(47) GonzalezꢀNunez, M. E.; Royo, J.; Mello, R.; Baguena, M.; Ferrer, J. M.; de Arellano, C. R.; Asensio, G.; Prakash, G.
K. S. J. Org. Chem. 2005, 70, 7919–7924.
(48) Janku, J. B.; Vodichka, L. Sb. Vys. Sk. Chem. Techn. 1984, D49, 25–38.
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