Silacyclohexanes and silaheterocyclohexanes—why are they so different from other heterocyclohexanes?

Tetrahedron 69 (2013) 5927e5936

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Silacyclohexanes and silaheterocyclohexanesdwhy are they so different from other heterocyclohexanes? Bagrat A. Shainyan a, *, Erich Kleinpeter b, * a b

A. E. Favorskii Irkutsk Institute of Chemistry, Siberian Division of Russian Academy of Science, 1 Favorsky Street, Irkutsk 664033, Russia €t Potsdam, Karl-Liebknecht-Str. 24-25, D-14476 Potsdam (Golm), Germany Chemisches Institut der Universita

a r t i c l e i n f o

a b s t r a c t

Article history: Received 21 February 2013 Received in revised form 11 April 2013 Accepted 26 April 2013 Available online 2 May 2013

Stereochemical studies on silaheterocyclohexanes is a ‘hot topic’ as evidenced by the growing number of publications. During last 10 years a substantial number of substituted silacyclohexanes and heterocyclohexanes containing sulfur, oxygen or nitrogen as the second (or third) heteroatom have been synthesized and studied by variable temperature dynamic NMR spectroscopy, gas-phase electron diffraction, variable temperature IR, Raman, microwave spectroscopy with respect to thermodynamic (frozen conformational equilibria) and kinetic (barrier to ring inversion) information. As the stereochemistry of cyclohexane and its N-, O-, P-, S-hetero analogues is one of keystones of modern theoretical and synthetic organic and heterocyclic chemistry, the stereochemistry of silacyclohexane and its hetero analogs is an important element of theoretical and synthetic organosilicon chemistry. The various classes of saturated six-membered rings were critically compared and studied in detail with respect to differences in their stereochemistry and dynamic behavior. Ó 2013 Elsevier Ltd. All rights reserved.

Keywords: Silacyclohexanes Silaheterocyclohexanes Conformational equilibrium Barrier to ring inversion Steric effects Electrostatic effects

1. Introduction In a contribution to Advances in Heterocyclic Chemistry in 20041 the conformational analysis of silacyclohexanes was reviewed. At that time not very many of them had been studied: silacyclohexane, 1,4-disilacylohexanes, and 1,3,5-tris-silacylohexanes both non-substituted as well as Si-alkyl substituted.2,3 The conformational analysis of the silacylohexanes studied that time established these compounds to occur as chair conformers with the substituents at silicon to prefer equatorial conformations.3 So even with the elongated SieC bond length and reduced CeSieC bond angles compared with the carbon analogues the principal stereochemical properties could be considered as similar to those of their carbon predecessors, cyclohexanes. The barriers to the chair-tochair interconversion in silacyclohexanes, however, due to the chair conformer being more flattened than the cyclohexane analogues, are much lower, and their measurement requires special solvents (liquid at very low temperatures and still dissolving the sample) and special NMR hardware (to calibrate probe temperatures at these low temperatures). Meanwhile the ring interconversion barriers can be measured now in special freon mixtures and peculiar probe heads, which can be calibrated down to 100 K; hereby barrier down to 4e5 kcal/mol get attainable.

* Corresponding authors. E-mail addresses: [email protected] (B.A. Shainyan), [email protected] (E. Kleinpeter). 0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.tet.2013.04.126

From the synthetic point of view, along the same period, many new silacyclohexanes and silaheterocyclohexanes have been synthesized and were studied by dynamic NMR spectroscopy, GED, IR, Raman, MW spectroscopy. The conformational equilibria could be frozen and barriers of chair-to-chair interconversion could be determined. In addition to silacyclohexane and polysilacyclohexanes, various Si-mono- and di-substituted derivatives were published and the effect of the Si-substituents on the conformational equilibria (DG
) and the barriers to ring inversion (DGs) could be established. In addition to silicon, other heteroatoms, such as nitrogen, oxygen and sulfur, were introduced into the saturated sixmembered ring system and again both DG
and DGs were determined and the dynamic NMR results obtained were examined with respect to the Perlin effect, the anomeric effect, and inherent substituent/heteroatom interactions/influences on both DG
and DGs in the light of parallel computational, Natural Bond Orbital (NBO), and Natural Chemical Shielding (NCS) studies. When comparing both substituent and heteroatom influences on the dynamic NMR parameters of the silacyclohexane derivates, a new quality of conception of conformational properties of substituted and heterosilacyclohexanes can be pursued. This is one aim and one object of the present paper. The basic question in the conformational analysis of the siliconcontaining heterocycles is if there is a principal difference in the conformational behavior of silaheterocyclohexanes and their carbon analogues. It is easy to show that such a difference does exist and can even lead to the reversal of conformational preferences. For

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example, 1-phenylcyclohexane exists exclusively as the equatorial conformer,4 whereas for 1-phenylsilacyclohexane 22% of the axial conformer are observed.5 Introduction of the sulfur atom into the bposition to the silicon atom shifts the conformational equilibrium of 1-phenylsilacyclohexane from eq/ax¼78%:22% to 95%:5% in 3phenyl-3-silathiane.5 Opposite conformational preferences are observed also in the geminally disubstituted cyclohexanes and silaheterocyclohexanes; thus, the PhaxMeeq conformer of 1-methyl1-phenylcyclohexane is more favorable (72:28),6 whereas the PheqMeax conformer predominates (63:37) in 1-methyl-1phenylsilacyclohexane.5 It is the second major object of this paper to investigate the effect of additional nitrogen, oxygen or sulfur heteroatoms in the cyclohexane analogues on both axial/equatorial conformation of substituents at silicon, nitrogen, and carbon atoms and the barrier to ring inversion of the saturated six-membered heterocyclic ring. Moreover, for geminally disubstituted cyclohexanes and silaheterocyclohexanes another question arises: are conformational effects of substituents additive or not in the various series of compounds? This topic deserves special consideration and will be studied as well. 2. Results and discussion 2.1. Silacyclohexanes Silacyclohexane itself was first studied theoretically in 2000 and the barrier to the chair-to-chair interconversion was found to be 5e6 kcal/mol dependent on the level of theory employed.7 In addition to the chair conformer, two different twist conformers were identified, which are w3 kcal/mol less stable; the mechanism of the ring inversion was suggested8 although debated after additional calculations.9 1,2-, 1,3-, and 1,4-Disilacyclohexanes were studied by gas-phase electron diffraction (GED) and at the MP2 and DFT levels of theory.10 Chair and twist forms were found to be minima and the boat conformations to be the transition states for the ring inversion process. The barriers to inversion of approximately 5 kcal/mol rank in the order 1,4->1,2->1,3-disilacyclohexane. Experimental (GED) and theoretical studies of 1,3,5-trisilacyclohexane, the intermediate between cyclohexane and cyclohexasilane, showed it to be closer to the latter from the viewpoint of the energy difference between the chair and a twist boat conformations equal to 2.2, 6.5, and 1.9 kcal/ mol for C3Si3H12, C6H12, and Si6H12, respectively.11,12 Symmetrically trissubstituted Si-alkylated analogues of 1,3,5trisilacyclohexane were studied theoretically and showed the equatorial preference of the alkyl groups, although much less pronounced for non-branched substituents than in the cyclohexane series: DE(axeeq)¼0.30.4 (Me), 0.40.5 (Et), w0.6 (i-Pr), 2.22.5 (t-Bu).3

RHSi

SiHR

R = Me; Et; i-Pr; t-Bu.

SiHR The simplest Si-substituted silacyclohexane, 1-methylsilacyclohexane was studied by microwave MW,13 temperaturedependent Raman spectroscopy,14,15 GED, and low-temperature 13 C NMR spectroscopy2 and showed a slight preference (0.23 kcal/mol from 13C NMR) for the equatorial conformation; the barrier to the ring inversion proved to be 5.8e5.9 kcal/mol. 1-Monosubstituted silacyclohexanes with various substituents (X¼F,16,17 Cl,18 Br,19 I,20 CF3,21 SiH3,15a SiCl3,15 Scheme 1) were studied theoretically and experimentally using MW and

temperature-dependent Raman spectroscopy (X¼F, CF3), GED (X¼F, Cl, Br, I, CF3), and 19F NMR spectroscopy (X¼F, CF3).15e21

X Si

Si

H

X = F, Cl, Br, I, CF3, SiH3, SiCl3.

X

H

Scheme 1.

For 1-silylsilacyclohexane, GED, 13C NMR, and Raman spectroscopy showed the ratio of the axial to equatorial conformers close to unity.15a On going to 1-X-silacyclohexanes with electronegative substituents X, for 1-fluorosilacyclohexane, MW spectroscopy shows a slight axial preference of 42 cm1 (or 0.12 kcal/mol).16 Raman spectroscopy gives the value of DH¼0.250.03 kcal/mol (depending on the medium).17 The conformational energy of the fluorine atom in 1-fluorosilacyclohexane was found to be 0.310.2 kcal/mol (GED).17 This is directly opposite to the equatorial preference of the fluorine atom in fluorocyclohexane (w0.3 kcal/mol).22 An even larger difference is observed for the chlorine analogue. The GED-measured value of A (A¼DG
¼RT ln K) for the chlorine atom in 1-chlorosilacyclohexane is 0.430.18 kcal/ mol,18 whereas in 1-chlorocyclohexane it is 0.530.02 kcal/mol (in various solvents).22 Variable temperature IR and Raman study showed the 69:31% predominance of the axial conformer at room temperature.18a Similarly, in 1-bromo- and 1-iodosilacyclohexane the GED-measured values of A are 0.820.3219 and 0.590.22 kcal/mol,20 respectively, whereas in 1-bromo- and 1-iodocyclohexane they are 0.48 and 0.49 kcal/mol,22 respectively. Thus, the axial preference of the halogen atoms in the series of 1-halosilacyclohexanes as compared to the corresponding halocyclohexanes increases from F (0.4e0.6 kcal/mol) to Cl (0.96 kcal/mol), I (1.08 kcal/ mol), and Br (1.3 kcal/mol). This characteristic difference in energy was attributed to electrostatic and hyperconjugation effects of the SieHal bond.18e20 The most striking effect is observed for the trifluoromethylsubstituted compounds. Whereas in trifluoromethylcyclohexane the A value of the CF3 group is 2.5 kcal/mol,22 in 1-trifluoromethylsilacyclohexane it is as low as 0.40.1 kcal/mol in solution (19F NMR, 17% axial) and becomes even negative in the gas phase: 0.190.29 kcal/mol (GED, 58% axial).21a Thus, the difference of conformational energies of the CF3 group as determined by NMR is 2.1 kcal/mol. Later on, the same authors reported that the assignment was erroneous and the correct value of A is 0.4 rather than þ0.4 kcal/mol.21b In our context, however, this means only that the difference of conformational energies of the CF3 group becomes even larger, 2.9 kcal/mol. A strong electrostatic effects in silacyclohexanes stemming from strongly electropositive silicon atom was clearly demonstrated by comparing the lengths of the SieCH2 and SieCF3 bonds in triA longer fluoromethylsilacyclohexane.21 The latter bond is 0.078  than the former due to repulsive interactions between the silicon atom and the partly positive charge of the trifluoromethyl carbon and attractive interactions between the silicon atom and the partly negative charge of the methylene carbon.21 Practically the same conclusion follows from comparison of the SieMe bond length in methylsilacyclohexane (1.862(4)  A) and SieCF3 bond in trifluoromethylsilacyclohexane (1.934(10)  A) with the difference of 0.072(11)  A. In a recent conformational study of 1-phenylsilacyclohexane by low temperature 13C NMR spectroscopy a substantial fraction

B.A. Shainyan, E. Kleinpeter / Tetrahedron 69 (2013) 5927e5936

heterocyclohexanes are subject to nature and position of the heteroatoms as well. In particular, the theoretically calculated conformational energy of the Me3Si group in 2-trimethylsilylthiane is 2.05 kcal/mol,27 which is 0.45 kcal/mol lower than in trimethylsilylcyclohexane. Another effect of the silicon atom in the saturated six-membered ring can be followed by comparing the conformational preferences of thiane S-oxides (Scheme 3) and silathiane S-oxides. The preponderant existence of thiane S-oxide in the axial form is well known.28 The introduction of two methyl groups at the 3-position of thiane S-oxide strongly disfavors the axial conformer due to re-

(21e22%) of the axial conformer was observed corresponding to the free energy difference of 0.22e0.25 kcal/mol,5 which is one order of magnitude lower than the conformational energy of the Ph group in phenylcyclohexane (2.87 kcal/mol).22 2.2. Thiasilacyclohexanes A large series of the Si,S-containing six-membered heterocycles (silathianes and their S-functional derivatives) with the heteroatoms separated by one or two methylene groups were synthesized and their conformational equilibria were studied (Chart 1).

R S

Si

R O S

Si

NSO2R

S(O)n

S

Si R = Me (1), Ph (2), SiMe3 (3)

R = H (4), Me (5)

H Me

Si

S

11

Me

H

Si

Me

R = Ph (9), CF3 (10)

n = 0 (6), 1 (7), 2 (8)

F

Si

5929

S

Ph

Si

12

S

Ph

Si

S

14

13 Chart 1.

In addition to the aforementioned conformational differences of the substituents at silicon, the enlarged size of the silathiane ring (due to elongated CeSi and CeS bond lengths, compared with CeC) also drastically diminishes the conformational energy of the substituents at the remaining carbon atoms. Thus, while the conformational energy of the methyl group in methylcyclohexane is 1.7 kcal/mol, the ratio of the 2-Meeq:2-Meax conformers of 2,3,3trimethyl-3-silathiane 1 is equal to 60:40, which corresponds to the free energy difference DG
of 0.35 kcal/mol (Scheme 2).23

Si

S

Si S

40%

60% Scheme 2.

The

theoretically

calculated

free

energy

difference

DG
¼0.36 kcal/mol exactly coincides with the experiment.23 Interestingly, in the carbon analogue, 2,3-dimethylthiane, the 2Meeqe3-Meax$2-Meaxe3-Meeq equilibrium is shifted to the left (61:39), in spite of practically equal conformational energies A for the 2-Me and 3-Me groups in thiane (1.42 and 1.40 kcal/mol).24 The nonadditivity was assigned to the difference in the interaction of the 2- and 3-Me groups due to different dihedral angles MeeCeCeMe in the two conformers, 57 and 52
, respectively.24 The presence of only one 1,3-syn-axial repulsive interaction between the 3-Meax and 5-Hax in the 2-Meeqe3-Meax conformer but two such interactions between the 2-Meax and 4-Hax and 6-Hax in the 2-Meaxe3-Meeq conformer should be another reason. 2-Phenyl-3,3-dimethyl-3-silathiane 225 and 2-tris-methylsilyl3,3-dimethyl-3-silathiane 323 are anancomeric with the conformational equilibrium fully shifted toward the corresponding equatorial conformers. Obviously, this is due to the large conformational energy A of the phenyl (2.8 kcal/mol)6 and trimethylsilyl group (2.5 kcal/mol)26 even in spite of the fact that A values in

O S S ax

O

eq Scheme 3.

pulsive interaction of SO-ax with the 3-Me-ax group, so that 3,3dimethylthiane 1-oxide exists exclusively as the SO-eq conformer.29,30 Its silicon analogue, 3,3-dimethyl-3-silathiane S-oxide 4 also exists in the solution as the single equatorial conformer.31 The situation is further complicated by introduction of another methyl group into the ring. Due to the presence of two chiral centers (C and S atoms) 2,3,3-trimethyl-3-silathiane S-oxide 5 can exist as two diastereomers. Indeed, a 1:2 mixture of the two diastereomers was obtained by oxidation of 1, which after separation on silica gel gave pure cis-5 and trans-5 isomers. The trans-isomer exists exclusively in the eqeeq form, whereas for the cis-isomer there is an equilibrium between the MeeqSOax and the MeaxSOeq conformers (Scheme 4). The ratio of the conformers is close to unity at room temperature but upon cooling to 120
C the axial

O Si

S

Si S

trans-5-ax,ax

O

trans-5-eq,eq

O Si

S

Si S

cis-5-MeeqSOax

cis-5-MeaxSOeq Scheme 4.

O

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B.A. Shainyan, E. Kleinpeter / Tetrahedron 69 (2013) 5927e5936

sulfoxide predominates, 5-MeeqSOax:5-MeaxSOeq¼5:1. The predominance of the 5-MeeqSOax conformer is due to the large conformational energy A of the methyl group (1.7 kcal/mol) and the small negative value of A of the sulfoxide group (0.18 kcal/mol). Although introduction of the silicon atom into the ring reduces the A value for the methyl group and makes the A value for the S]O group positive, the 5-MeeqSOax conformer still remains preferable, although only at low temperatures. The barrier to ring inversion for the process 5-MeeqSOax/5MeaxSOeq at 100
C was measured to be 8.1 kcal/mol, and 7.5 kcal/ mol for the reverse process 5-MeaxSOeq/5-MeeqSOax.31 These values are about half of that reported for the ring inversion of thiane S-oxide (14.2 kcal/mol).32 For silathiane 6 and silathiane S,S-dioxide 8 the ring inversion is degenerate and the barriers are very low, 4.8 and 5.0 kcal/mol, respectively, and practically concide with the theoretically calculated barriers of 4.6 kcal/mol in 6 and 4.5 kcal/mol in 8.33 The low to extremely low barriers to ring inversion of the sila-derivatives are certainly the result of the both the elongated CeSi bonds and the smaller degree of folding of the sila-analogues. As distinct of that, the conformational equilibrium of silathiane S-oxide 7 is not degenerate (Scheme 5). Both conformers are observed in chloroform solution, the equatorial being predominant with the ratio 7-eq:7-ax¼63:37. This result is quite comparable with the 55:45 ratio of the equatorial and axial conformer of thiane S-oxide.30

Fig. 1. The reaction coordinate of the chair-to-chair interconversion of the axial and equatorial conformers of 4,4-dimethyl-4-silathiane S-oxide 7 (for the relative energies of the stationary points see the text).

the chair, twist, and boat conformers of 4-silathiane 1-oxides with one or two halogen atoms at silicon were calculated34e36 and summarized in Ref. 37. Of special interest are the boat conformers of the axial sulfoxides since they are capable of formation of pentacoordinate structure.

X

O S

Si Y

O S

Si

Si

S 7-ax

O

7-eq Scheme 5.

Noteworthy, DFT calculations at the B3LYP/6-311þG(d,p) level of theory seem to be in contradiction with the experiment since they give a higher stability of the axial conformer 7-ax by 0.93 kcal/mol. However, the higher dipole moment of the equatorial conformer (5.41 vs 4.21 D) prompted us to examine the solvent effect.33 The use of the PCM model at the same level of theory and chloroform as the solvent showed that the 7-eq conformer becomes 0.19 kcal/mol more stable, which corresponds to the equilibrium ratio 7-eq:7-ax of 70:30. This is in excellent agreement with the experimental ratio of 63:37.33 The experimental barrier to interconversion of the axial and equatorial conformers of compound 7 is 4.8 kcal/mol. Note that the process does not proceed as the inversion at the sulfur atom although the transition state with the planar trigonal sulfur atom and one imaginary frequency of 563i cm1 connecting the axial and equatorial chair conformers was localized on the potential energy surface (PES). Its energy with respect to 7-ax or 7-eq (i.e., the inversion barrier) is too high (46 kcal/mol). Instead, the chairechair interconversion proceeds via the two identical intermediate 1,4twist forms, which are interconverted via a shallow 2,5-boat transition state with the imaginary frequency of 40i cm1. The process includes the reaction sequence 7-ax (chair)$7 (1,4-twist)$[7 (2,5-boat)]s$7 (1,4-twist)$7-eq (chair) as shown in Fig. 1.33 The calculated barriers are 5.1 (7-ax/7-eq) and 4.2 kcal/mol (2eq/2-ax) in the gas phase, and 4.03 and 4.22 kcal/mol in chloroform, respectively, and are in good agreement with the experimental values of 4.8 kcal/mol. The sulfoxide 7 and its analogues with different substituents at silicon, as well as all other silacyclohexanes studied so far normally exist in the chair conformation. Geometries and relative energies of

The term ‘scorpionoids’ was coined for these structures with the silicon atom as the head and the oxygen of the sulfoxide group as the stinging tail.34 These boat conformations are local minima on the PES, whereas in the absence of the S]O/Si interaction they are either transition states or do not correspond to any stationary point on the PES at all. For various combinations of halogens X and Y (X, Y¼H, F, Cl, Br) the O/Si distance proved to vary within the range 2.05e2.15  A,37 which is much lower than the sum of the van der Waals radii of the O and Si atoms (3.62  A). The pentacoordination is also proved by planarization of the C,C,X equatorial arrangement of the silicon atom, and elongation of the axial SieY versus the equatorial SieX bond in the silicon bipyramid.34e37 We know of only one experimental study on the coordination of the sulfinyl oxygen with silicon to generate a hypervalent trigonal bipyramidal structure.38 Sulfimides 9 and 10, which are isoelectronic analogues of sulfoxide 7, are also characterized by very low activation barriers of 4.7 and 4.4 kcal/mol, respectively.39 For sulfimide 9, the conformational equilibrium is practically degenerate (eq/ax w1:1), whereas the electronegative trifluoromethyl group not only facilitates the ring inversion but also slightly increases the relative stability of the axial conformer (eq/ax w45:55).39 Note that apart from the axial or equatorial position of the sulfimide nitrogen atom the conformers may differ by the ‘inward’ or ‘outward’ directed CF3 group. For the carbon analogue of N-phenyl-4,4-dimethyl-4-silathiane 1-sulfimide 9, the X-ray diffraction analysis has shown the ‘outward’ structure of the corresponding axial sulfimide.40 The conformational analysis of 3-methyl-3-silathiane 11 has shown the preference of the equatorial conformer, ax/eq¼15:85, corresponding to a free energy difference (A value) of 0.35 kcal/mol (Scheme 6).41 In comparison with the corresponding mono-hetero cyclohexanes, this value is somewhat greater than in 1-methyl-1-silacyclo hexane (0.23 kcal/mol)2 but much less than in 3-methylthiane

B.A. Shainyan, E. Kleinpeter / Tetrahedron 69 (2013) 5927e5936

For example, silathianes and their S-functional derivatives fall in between the range of 4.4e6.3 kcal/mol, which is substantially lower than for cyclohexane (10.3 kcal/mol)46 or thiane (9.4 kcal/mol).47 The higher flexibility of the Si-containing heterocycles is usually attributed to the longer SieC (1.87  A) as compared to the CeC bond (1.54  A). However, the SeC bond (1.82  A) is nearly of the same length as the SieC but the difference between the ring inversion barriers in silathianes and thianes still remains rather high. It seems reasonable to assume that another effect responsible for the higher flexibility of the Si-containing cycles is the less folding angles of the ‘Si-part’ of the ring than those of its ‘C-’ ‘N-’ ‘O-’ or ‘S-part’. Thus, both the experiment and theoretical calculations give the angles of folding of the ‘Si-part’ (40
) being substantially lower than that of the other part of the chair conformer (60
), which must, and does, facilitate the ring inversion.

Me Si S

X

S

ax

Me

Si X

eq

X = H (11), F (12) Scheme 6.

(1.40 kcal/mol).24 Unexpectedly, for 3-fluoro-3-methyl-3-silathiane 12 the conformational equilibrium is energetically degenerate, ax/eq¼50:50.41 A detailed analysis of the experimental and theoretical conformational energies of compounds 11, 12 and the similarly substituted monoheterocyclohexane analogues led to the conclusion that the situation is not as simple as if it were determined only by the conformational energies of the substituents at the silicon atom.41 Donoreacceptor interactions between the appropriately oriented vicinal CeX bonds, which are quantitatively characterized by the corresponding second order perturbation energies in the NBO analysis, were also shown to play a role in stabilizing or destabilizing the axial and equatorial conformers of di- and triheterocyclohexanes.41 The SiePh substituted silathianes 13, 14 (cf. Chart 1) are of special interest because (i) except for our recent work5 they have never been conformationally studied, and (ii) they are qualitatively different from the methyl- or halogen-substituted analogues since the phenyl group is an asymmetric rotor and its rotation may (and does) cause strong variations of nonbonded intramolecular interactions, as was shown for the similarly substituted phenylcyclohexanes.24,42e45 The conformational analysis of silathianes 13, 14 as well as their ancestor, 1-phenylsilacyclohexane, allowed us to estimate the conformational energy A for the phenyl group at-

Si

N Si

O

Si o ~40 ~60o

2.3. Si,N- and Si,N,O-heterocyclohexanesdcomparison with piperidines and morpholines For a number of the Si,N- and Si,N,O-heterocyclohexanes presented in Chart 2 the conformational preferences were studied and the barriers to ring inversion measured. These data can be compared, on the one hand, with those of the Si,S-cycles listed in Chart 1 to follow the effect of the second (and third heteroatom), and, on the other hand, with their carbon analogues such as piperidines and morpholines.

SO2CF3

SO2CF3 Si

R O

R = Me (15), i-Pr (16)

5931

N

N

N Si

Ar

Si

17

18

Si HO

Y Si

N

O

R

X

Si

19 CH2OH

N

R = Me, X = H, Y = Me (23) R = X = Y = Me (24) R = i-Pr, X = Y = Me (25) R = X = Me, Y = Ph (26) R = i-Pr, X = Me, Y = Ph (27) R = X = Me, Y = i-PrO (28)

O

O

R Me2Si

R = Me (20) Bn (21) Ph (22)

R

N

SiMe2

29

Chart 2.

tached to silicon to be as low as w0.25 kcal/mol, that is, one order of magnitude less than in phenylcyclohexane (2.87 kcal/mol).5 The conformational composition of 3-phenyl-3-silathiane 13 was 95:5 at 103 K and 75:25 at 296 K, and that of 3-methyl-3-phenyl-3silathiane 14 was 68:32, all in favor of the Pheq conformer. The barriers to ring inversion in various SiePh substituted silaheterocyclohexanes lie within the range of 5.2e6.0 kcal/mol.5 As follows from the above analysis, the barriers to ring inversion of silaheterocyclohexanes are substantially lower than those of cyclohexanes or heterocyclohexanes containing no silicon atoms.

The measured ring inversion barriers of 4-methyl- (15) and 4-ipropyl-2,2,6,6-tetramethyl-1,4,2,6-oxaazadisilinane (16) are equal to 8.5 and 7.7 kcal/mol,48 respectively that is lower than in the less crowded N-methylmorpholine having no methyls in the 2 and 6 positions (DGz¼11.1 kcal/mol).49,50 As mentioned above, this is the result of the longer SieC bonds relative to CeC and the more flattened ‘SieOeSi part’ of the molecules. In 2,2,6,6-tetramethyl-4-(trifluoromethylsulfonyl)-1,4,2,6-oxazad isilinane 17, the N-triflyl analogue of 15 and 16, the nitrogen atom is almost planar due to the strong acceptor effect of the triflyl group. Still,

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as in other six-membered heterocycles with the endocyclic nitrogen atom bearing the triflyl group,51e53 two rotamers, namely, those with the CF3 group directed ‘inward’ or ‘outward’ of the ring can exist. The energy difference between the two rotamers calculated at the MP2/6311(d,p) or B3LYP/6-311(d,p) level of theory is 1.1 kcal/mol in favor of the latter, the ‘outward’ rotamer of 17; this was proved for the solid state by X-ray analysis.54

piperidines to silapiperidines.55e58 Unfortunately, low temperature NMR conformational studies for these compounds were not performed. For another type of the Si,N,O-heterocycles, 4-alkyl(phenyl)-2,2dimethyl-1,4,2-oxaazasilinanes 20e22, the measured barriers to ring inversion gradually decrease with increasing conjugation of the nitrogen lone pair with the exocyclic substituent R: DGz¼8.85 (Me), 7.7 (Bn), 4.8 (Ph) kcal/mol.59 The substituent R in 20e22 is always equatorial, which, apart of the equatorial conformer being w5 kcal/mol more stable than the axial, is proved by good coincidence of the experimental 15N chemical shifts with those calculated for the equatorial conformers [within 0.3e2.0 ppm at the GIAOeB3LYP/6-311G(d,p) level] and strong deviation from the calculated for the axial conformers (up to 18 ppm).59 Quaternization of the free bases 20 and 21 with methyl iodide gave the corresponding salts for one of which single crystals suitable for X-ray were grown. The experimental structure of the salt (ORTEP view, left) fully coincides with the MP2/6-311G(d,p) optimized structure of its cation (right).59

For another N-triflyl substituted compound of this type, 1trifluoromethylsulfonyl-4,4-azasilinane 18, the energetic preference of the ‘outward’ over the ‘inward’ rotamer at the MP2/6311(d,p) level is 0.6 kcal/mol, or twice as low as that for 17.54 This energy difference corresponds to the ratio of ca. 95:5 and suggests that the equilibrium may be strongly but not fully biased to the ‘’outward’ conformer (Scheme 7). F 3C

O S

N

O S

O O

N

CF3

Si

Si

outward

inward Scheme 7.

Indeed, low temperature 13C NMR spectroscopy showed the presence of two conformers in the ratio of ca. 50:1. Thus, the experimental ratio of 98:2 is nicely consistent with the theoretically predicted ratio of 95:5.54 The experimental barriers to ring inversion of both compounds 17 and 18 were found to be 12.7 and 13.1 kcal/mol, respectively. This poses an interesting question: why are the barriers to ring inversion in the N-triflyl derivatives 17 and 18 (which apart from having longer SieC bonds and a flattened ‘Si-part’ of the ring have also a planarized nitrogen atom) higher not only as in the N-alkyl derivatives 15 and 16, but even larger than in N-methylmorpholine itself? The answer, in our opinion, is that the ring inversion of 17 or 18 makes the ‘outward’ CF3 group to become ‘inward’ and vice versa. It is unavoidably followed by its rotation about the NeS bond to adopt the most stable conformation and, as the overall rate of a reaction cannot exceed the rate of the slowest elementary step, the total energy for the ring inversion cannot be lower than that required for each step of the conformational equilibrium. The barrier to rotation in the N-triflyl heterocycles, as was shown earlier, is of about the same size (12e14 kcal/mol).51e53 4-Silapiperidines 19, bearing hydroxy and aryl groups at the same silicon atom, as well as their hydrochloric salts, were studied by Tacke et al.,55e58 who showed them to adopt a chair conformation with equatorial N-organyl group and a flattened ‘Si-part’ of the ring, as it is the case for all other silacyclohexanes and silaheterocyclohexanes. The ammonium salts 19$HCl exist as mixtures of two isomers in the ratio much lower than that for their carbon analogues, which allowed the authors to conclude that the energy difference between the two isomers decreases on going from

For the dimethyl salt the degenerate ring inversion could not be frozen down to 103 K, but for the Me,Bn-salt the barrier of 6.1 kcal/ mol was measured. In the latter case the ring inversion is not degenerate and the ratio of the conformers was measured to be MeaxBneq:MeeqBnax¼60:40, which suggest a low energy difference between the two conformers. Theoretical analysis of the corresponding cations has shown that at the DFT level the energy difference DE is 0.93 kcal/mol in favor of the MeaxBneq conformer, but the MP2 calculations showed the two conformers to be energetically identical within 0.01 kcal/mol, which can be considered as more or less consistent with the experiment.59 A series of 1,3-azasilinanes 23e28 with different substituents both at the nitrogen and the silicon atom were studied as well. The intramolecular flexibility should include both ring inversion and nitrogen inversion (Scheme 8).

Si

N

ring inversion

Si N

nitrogen inversion

Si

N

nitrogen inversion ring inversion

Si N

Scheme 8.

However, due to the much lower energy of the NReq versus NRax conformers48,59e63 and the N-inversion being still fast on the NMR time scale at lowest temperatures, the observed conformational equilibrium NRax$NReq is completely biased to the NReq conformers (cf. Scheme 9).

B.A. Shainyan, E. Kleinpeter / Tetrahedron 69 (2013) 5927e5936

Si

N

Si N Scheme 9.

The simplest representative, 1,3-dimethyl-1,3-azasilinane 23 exists as an equilibrium mixture SiMeax:SiMeeq of w1:2 composition (33%:67% by 1H, 30%:70% by 13C) in solution, as follows from the low temperature 1H and 13C NMR study.64 However, in the gas phase (GED, IR) the axial conformer of compound 23 predominates with the ratio SiMeax:SiMeeq of w2:1.64 This corresponds to the equilibrium constant K¼2.1 and the conformational free energy DG0¼0.21 kcal/mol, which is significantly less than in 1,3dimethylpiperidine (K¼99.9 at 173 K, DG0¼1.6 kcal/mol)62 but practically coincides with 1-methyl-1-silacyclohexane (0.23 kcal/ mol).2 Thus, the effect of the nitrogen atom on the barrier to ring inversion of 1,3-dimethylpiperidine (1.60 kcal/mol vs 1.76 kcal/mol in methylcyclohexane) is small (w10%) but still notable, whereas in silaheterocyclohexanes the same effect is 0.02 kcal/mol only and negligible. 1,3,3-Trimethyl-1,3-azasilinane 24 is the first Si,N-heterocycle for which the structure was obtained by the gas electron diffraction method.60

High-level calculations at the DFT and MP2 levels with the augcc-pVTZ basis set, and at the G2 level allowed to reproduce the GED bond lengths to 0.006  A, bond angles to 1.2
, and dihedral angles to 1.2
. The molecule exists in a slightly distorted chair conformation with the N-Me group in equatorial position. As for the Si,S-heterocycles (vide supra), the puckering of the ‘Si-part’ of the ring is much less than that of its ‘N-part’: the flap angle between the plane C2eSi3eC4 and the average plane N1eC2eC4eC5 is ca. 40
(slightly varying with the method of calculation) and the angle C6eN1eC2/C2eSi3eC5eC6 is ca. 60
. No traces of the N-Me axial conformer were detected by GED or low temperature NMR down to 103 K. This is consistent with a large energy difference of ca. 5 kcal/mol between the NMeax and NMeeq conformers.60 The barrier to ring inversion DGz of compound 24 of 9.1 kcal/mol is lower than that in N-methylpiperidine (14.4 kcal/ mol) or 1,3,3-trimethylpiperidine (10.8 kcal/mol) due to the longer SieC as compared to the CeC bonds in the carbon analogues. Replacement of NMe in 24 by N-iPr in 25 lowers the barrier to ring inversion by 0.8 kcal/mol (to 8.25 kcal/mol) due to continued planarization of the nitrogen atom by the branched alkyl group; this is confirmed by theoretical calculations.60,61,65 For the Si-chiral azasilinanes 26 and 27, the conformational equilibrium is not degenerate, the ratio of the conformers is

5933

w67:33 for 2661 and 58.5:41.5 for 27,65 in both cases in favor of the Pheq,Meax conformers. The barriers to ring inversion DGz were measured to be 9.0 kcal/mol in 1,3-dimethyl-3-phenyl-1,3azasilinane 2661 and 8.25 kcal/mol in 1-i-propyl-3-methyl-3phenyl-1,3-azasilinane 27.65 1,3-Dimethyl-3-isopropoxy-3-silapiperidine 28 is not only the first Si-alkoxy substituted Si,N-heterocycle but also the first conformationally studied silaheterocyclohexane with an electronegative substituent at the silicon atom (cf. Scheme 10).66

Scheme 10.

Low temperature 1H and 13C NMR spectroscopy revealed that in spite of much lower A-values for OR groups as compared to the Me group both in cyclohexanes22 and in silacyclohexanes67e69 the Meaxi-PrOeq conformer predominates in the equilibrium in the ratio Meaxi-PrOeq:Meeqi-PrOax of ca. 2:1. This result is in contrast to all expectations, and the question is, why? In the geminally disubstituted cyclohexanes, the group with the larger A value proves to be equatorial and the one with smaller A value to be axial.70 In monosubstituted silacyclohexanes, first, the equatorial preference is substantially decreased for all substituents, and, second, electronegative substituents additionally strengthen the axial orientation.18e20,67,69 The number of representatives of Si-disubstituted silaheterocyclohexanes is very small but the unequivocal conclusion that can be drawn is that in all so far studied compounds the substituents with larger A-values still prefer the equatorial position.5,41,61,65,69 Hence, the observed inversion of the conformational preferences in 28 inevitably must be assigned to the presence of the nitrogen atom in the ring. Repulsion of the two unidirectional axially oriented dipoles of the nitrogen atom lone pair and of a highly polar SieO bond destabilizes the Meeqi-PrOax conformer and makes the Meaxi-PrOeq conformer predominant. This effect must be of special importance in Si-alkoxy(hydroxy) 3-silapiperidines because of (i) a larger dipole moment of the SieO versus CeO bond and (ii) a higher basicity of nitrogen in a-silylamines relative to organic amines.71e73

X Si N

Me

The thermodynamic parameters shown in Scheme 10 were obtained by complete line shape analysis and clearly prove that the barrier to ring inversion arises mainly from the entropy term of the free energy of activation.66 A special and very interesting example of the conformationally studied Si,N,O-heterocycles is the silicon analogue of quinolizidine, (3,3,7,7-tetramethylhexahydro-1H-[1.4.2]oxazasilino[4,5-d][1.4.2] oxaazasilin-9a-yl)methanol 29, synthesized by simple reaction of tri(hydroxymethyl)aminomethane with (chloromethyl)(methoxy) dimethylsilane.74

5934

B.A. Shainyan, E. Kleinpeter / Tetrahedron 69 (2013) 5927e5936

CH2OH H2NC(CH2OH)3 + 2 ClCH2SiMe2OMe

DBU

O

O

benzene, rt,

N

Me2Si Compound 29 turned out to be conformationally flexible with a low activation barrier of 5.8 kcal/mol. This might be suggestive of the cis-fused structure of the two rings since in the full-carbon analogue, decalin, the ring inversion is possible only in the cisisomer, whereas the framework of the trans isomer is locked. However, in N-fused azabicycles like quinolizidine, the nitrogen inversion gets possible and hereby also cis/trans isomers can interconvert (Scheme 11).

N N

Scheme 11.

Indeed, X-ray structural analysis revealed the trans,trans-fused configuration in the solid state.74

Quaternization of the nitrogen atom in 29 stops the N-inversion and the isomeric quaternary ammonium salts do not undergo interconversion. The 9a-R-substituted quinolizidines give with MeI a mixture of the trans and cis isomers of the corresponding salts, the fraction of the trans isomer decreasing in the order: H>CN>CH3>CH2OH>CH2NO2. Compound 29 gives the corresponding ammonium salt in close to quantitative total yield and with the trans/cis ratio of 1:1.2 (Scheme 12).74 This is substantially different from the ratio of 1:5 for its carbon analogue 9a-hydroxymethylquinolizidine iodomethylate.75

SiMe2

2.4. Si-chiral silaheterocyclohexanesdadditivity of the conformational effects The problem of additivity of the conformational free energies of the substituents, which until recently was confined to cyclohexane derivatives only, can be traced back to the 60s of the last century76 but is still the subject of research including new objects and methods.77e79 For cyclohexanes, the lack of additivity was concluded to be the rule.80 The most vivid example is 1-methyl-1-phenylcyclohexane (vide supra) existing predominantly as the PhaxMeeq conformer in spite of the larger A value for the Ph group. Recently, based on high-level calculations of monosubstituted silacyclohexanes and mono- and disubstituted cyclohexanes, it was concluded that for the equally disubstituted rings the additivity concept works only moderately well for the cyclohexanes and remarkably well for silacyclohexanes within a limited selection of substituents.69 Still, as follows from the analysis of the literature, even in the cyclohexane series the additivity is fulfilled for a limited range of the substituents.80 Table 1 summarizes the data allowing to compare the additivity of conformational effects of comparable substituents on cyclohexane and heterosilacyclohexanes. Even a brief inspection of Table 1 reveals that, in general, deviations from additivity are much larger for the cyclohexane than for the silacyclohexane series. This might seem to be fully consistent with the conclusion made by Arnason et al.,69 unless there was a good deal of evidence of additivity even in the cyclohexane seriesdsee examples with DDG
<0.1 kcal/mol in Table 1, as well as 1-vinyl- and 1-ethynyl-1cyclohexanols.70 Therefore, the lack of additivity in cyclohexanes cannot be considered as a general rule although the trend when comparing with silacyclohexanes is evident. The next important issue is the aforementioned specific behavior of substituents, which are asymmetric rotors, like Ph, whose rotation about the CePh or SiePh bond is affected by the second geminal substituent leading to substantial variations in energy, as proved by the largest deviations from additivity (Table 1, DDG
¼1.36e1.84). It may even reverse the positions of the two substituents in the preferable conformer relative to the predicted single conformational energies, like in 1-methyl-1phenylcyclohexane, 1-methyl-1-phenylcyclohexanol, or 1-(dimethylamino)-1-phenylcyclohexane. It is also meaningful that the presence of a heteroatom in a position remote from an endocyclic carbon atom bearing two substituents practically does not alter the situation observed for cyclohexanes: deviations for 3-methyl-3phenylthiane and 3-methyl-3-fluorothiane are large, being maximum for the former (Table 1).

O

CH2OH 29

benzene, rt,

O

O

MeI Me2Si

N I

SiMe2

Me

SiMe2

O

+ Me2Si

CH2OH N Me

Scheme 12.

I

B.A. Shainyan, E. Kleinpeter / Tetrahedron 69 (2013) 5927e5936

5935

Table 1 Additivity of substituent effects in geminally disubstituted cyclohexanes and heterocyclohexanes, kcal/mol (DG
add is the algebraic sum of DG
for the corresponding monosubstituted species)

X

X

Si Y X

Y b

Me

F

Me

CF3b

Me Me Ph Me

Me

Y

Z DG




axeeq

a

DG




add

DDG




Ref.

Z

X

Y

DG

69

CH2

Me

F




axeeq

a

DG
add

DDG


Ref.

0.36 0.52 0.63

0.10 0.24 0.24

69 41 69

1.60 1.38 1.31 0.76 1.13 0.21 1.34 1.14

0.74 0.52 0.78 0.23 1.45 0.61 1.84 0.07

69

CH2

Me

CF3

0.26 0.28 0.39

Ph NMe2 NMe2 Cl

0.86 0.86 0.53 0.53 0.32 0.4 0.5 1.07

42,45 81 82 70

CH2 CH2 S S

Me Cl Me Me

Ph SiCl3 Ph Fd

0.11 0.15 0.15 0.78

0.02 4.64c 0.25 0.79

0.09 4.79 0.10 0.01

5 15 5 41

Br

1.19

1.17

0.02

70

0.10

1.46

1.36

5

0.13

0.46

0.59

41

Ph d

S Me

OH

0.31

0.73

0.42

83,84

Me

OAc

0.775

0.85

0.075

70

Me

Me d

S

Ph a b c d

OH

0.5

1.86

1.36

F

80

‘ax’ refers to conformers with XaxYeq, ‘eq’dwith XeqYax. CCSD(T)/CBS calculated DE values are given. Theoretically calculated values from Ref. 68. B3LYP/6-311G** calculated DG values are given.

3. Summary Both the conformational equilibria and the barriers to ring interconversion of silacyclohexanes, exemplary three groups of recently synthesized silaheterocyclohexanes (thiasilacyclohexanes, Si,N- and Si,N,O-heterocyclohexanes, respectively, and Si-chiral silaheterocyclohexanes) were compared with the carbon- and other heteroanalogous six-membered ring compounds. The following general conclusions could be drawn: (i) Strong electrostatic and hyperconjugative effects of SieC, SieCF3 and esp. SieHal bonds, stemming from the strongly electropositive silicon atom, dominate the conformational equilibria of the corresponding silicyclohexanes. (ii) In addition, the enlarged size of the silacyclohexane ring [due to elongated CeSi (1.87  A) compared with CeC bonds (1.54  A) and slightly decreased CeSieC bond angles] also drastically diminishes the conformational energy of the substituents at the remaining carbon atoms; often completely different conformational equilibria (free rotation of Siephenyl substituents, negligible 1,3-diaxial interactions) were established. Low to extremely low barriers to ring inversion of the sila-derivatives (flattened chair conformation in the CeSieC part of the ring) were obtained. (iii) Silacyclohexanes with an endocyclic nitrogen atom bearing the triflyl group exist as two chair conformers/rotamers with the CF3 group directed ‘inward’ or ‘outward’ of the six-membered heterocyclic ring; the ‘outward’ conformer is usually strongly preferred but the equilibrium not fully biased. (iv) The effect of the nitrogen atom on the barrier to ring inversion of 1,3-dimethylpiperidine compared with the one of methylcyclohexane is small but still notable, whereas in silaheterocyclohexanes the same effect is negligible. (v) In geminally disubstituted cyclohexanes, the group with the larger A value proves to be equatorial and the one with the smaller A value to be axial. In monosubstituted

silacyclohexanes, however, the equatorial preference is substantially decreased for all substituents and electronegative substituents additionally strengthen the axial orientation. (vi) Deviations from additivity of the conformational free energies of substituents are much larger for the cyclohexane than for the silacyclohexane series, although the lack of additivity in cyclohexanes cannot be considered as a general rule; the trend when comparing with silacyclohexanes is evident. Acknowledgements The financial support of this work by the Russian Foundation for Basic Research and Deutsche Forschungsgemeinschaft (Grants RFBR-DFG 08-03-91954 and 11-03-91334) is greatly acknowledged. References and notes 1. Kleinpeter, E. Adv. Heterocycl. Chem. 2004, 86, 41e126. 2. Arnason, I.; Kvaran, A.; Jonsdottir, S.; Gudnason, P. I.; Oberhammer, H. J. Org. Chem. 2002, 67, 3827e3831. 3. Arnason, I.; Matern, E. J. Mol. Struct. (Theochem) 2001, 544, 61e68. 4. Squillacote, M. E.; Neth, J. M. J. Am. Chem. Soc. 1987, 109, 198e202. 5. Shainyan, B. A.; Kleinpeter, E. Tetrahedron 2012, 68, 114e125. 6. Eliel, E. I.; Manoharan, M. J. Org. Chem. 1981, 46, 1959e1962. 7. Arnason, I.; Torarinsson, E. Z. Anorg. Allg. Chem. 2000, 626, 853e862. 8. Freeman, F.; Fang, C.; Shainyan, B. A. Int. J. Quantum Chem. 2004, 100, 720e732.  Bodi, A. Int. J. Quantum Chem. 2006, 106, 1975e1978. 9. Arnason, I.; Kvaran, A.; € rnsson, R.; Oberhammer, H. J. Phys. Chem. A 2011, 10. Arnason, I.; Gudnason, P. I.; Bjo 115, 10000e10008. 11. Arnason, I.; Torarinsson, E. J. Mol. Struct. (Theochem) 1998, 454, 91e102. 12. Arnason, I.; Oberhammer, H. J. Mol. Struct. 2001, 598, 245e250.  Organometallics 13. Favero, L. B.; Velino, B.; Caminati, W.; Arnason, I.; Kvaran, A. 2006, 25, 3813e3816. 14. Klaeboe, P.; Horn, A.; Nielsen, C. J.; Aleksa, V.; Guirgis, G. A.; Wyatt, J. K.; Dukes, H. W. J. Mol. Struct. 2013, 1034, 207e215.  €lbling, M.; Dzambaski, B.; Flock, M.; Hassler, K.; Wallevik, S. O.; 15. (a) Kern, T.; Ho Arnason, I.; Bjornsson, R. J. Raman Spectrosc. 2012, 43, 1337e1342; (b) Wallevik,  Jonsdottir, S.; Antonsson, E.; Belyakov, A. V.;  Bjornsson, R.; Kvaran, A.; S. O.; Baskakov, A. A.; Hassler, K.; Oberhammer, H. J. Phys. Chem. A 2010, 114, 2127e2135.

5936

B.A. Shainyan, E. Kleinpeter / Tetrahedron 69 (2013) 5927e5936

 J. Phys. Chem. A 16. Favero, L. B.; Velino, B.; Caminati, W.; Arnason, I.; Kvaran, A. 2006, 110, 9995e9999.  Jonsdottir, S.; Antonsson, E.; Wallevik, S. O.;  Arnason, I.; 17. (a) Bodi, A.; Kvaran, A.; €lbling, M.; Oberhammer, H. Organometallics Belyakov, A. V.; Baskakov, A. A.; Ho 2007, 26, 6544e6550; (b) Klaeboe, P.; Aleksa, V.; Nielsen, C. J.; Horn, A.; Guirgis, G. A.; Johnston, M. D. J. Mol. Struct. 2012, 1015, 120e128. 18. (a) Belyakov, A. V.; Baskakov, A. A.; Naraev, V. N.; Rykov, A. N.; Oberhammer, H.;  Russ. J. Gen. Chem. 2011, 81, 2257e2261; (b) Aleksa, Arnason, I.; Wallevik, S. O. V.; Guirgis, G. A.; Horn, A.; Klaeboe, P.; Liberatore, R. J.; Nielsen, C. J. Vib. Spectrosc. 2012, 61, 167e175. 19. Belyakov, A. V.; Baskakov, A. A.; Naraev, V. N.; Rykov, A. N.; Oberhammer, H.;  Russ. J. Phys. Chem. A 2011, 86, 1563e1566. Arnason, I.; Wallevik, S. O. 20. Belyakov, A. V.; Baskakov, A. A.; Berger, R. J. F.; Mitzel, N. W.; Oberhammer, H.;  J. Mol. Struct. 2012, 1012, 126e130. Arnason, I.; Wallevik, S. O. 21. (a) Girichev, G. V.; Giricheva, N. L.; Bodi, A.; Gudnason, P. I.; Jonsdottir, S.;  Arnason, I.; Oberhammer, H. Chem.dEur. J. 2007, 13, 1776e1783; (b) Kvaran, A.; Girichev, G. V.; Giricheva, N. L.; Bodi, A.; Gudnason, P. I.; Jonsdottir, S.; Kvaran,  Arnason, I.; Oberhammer, H. Chem.dEur. J. 2009, 15, 8929. A.; 22. Bushweller, C. H. In Conformational Behavior of Six-membered Rings. Analysis, Dynamics, and Stereoelectronic Effects; Juaristi, E., Ed.; Wiley-VCH: New York, NY, 1995; pp 25e58. 23. Kirpichenko, S. V.; Kleinpeter, E.; Shainyan, B. A. J. Phys. Org. Chem. 2010, 23, 859e865. 24. Willer, R. L.; Eliel, E. L. J. Am. Chem. Soc. 1977, 99, 1925e1936. 25. Anteunis, M. J. O.; Dedeyne, R. Org. Magn. Reson. 1977, 9, 127e132. 26. Kitching, W.; Olszowy, H. A.; Drew, G. M.; Adcock, W. J. Org. Chem. 1982, 47, 5153e5156. 27. Freeman, F.; Phornvoranunt, A.; Hehre, W. J. J. Phys. Org. Chem. 1999, 12, 176e186. 28. Juaristi, E.; Ordonez, M. In Organosulfur Chemistry; Page, P., Ed.; Academic Ltd.: London, 1998; Chapter 3 and references therein, pp 64e95. 29. Lambert, J. B.; Bailey, D. S.; Mixan, C. E. J. Org. Chem. 1972, 37, 377e382. 30. Barbarella, G.; Dembech, P.; Tugnoli, V. Org. Magn. Reson. 1984, 22, 402e407. 31. Kirpichenko, S. V.; Albanov, A. I.; Pestunovich, V. A. J. Sulfur Chem. 2004, 25, 21e27. 32. Lambert, J. B.; Keske, R. G. J. Org. Chem. 1966, 31, 3429e3431. 33. Shainyan, B. A.; Suslova, E. N.; Kleinpeter, E. J. Phys. Org. Chem. 2011, 24, 1188e1192. 34. Freeman, F.; Asgari, N.; Entezam, B.; Gomarooni, F.; Mac, J.; Nguyen, M. H.; Nguyen, N. N. T.; Nguyen, T. P.; Pham, N. B.; Sultana, P.; Welch, T. S.; Shainyan, B. A. Int. J. Quantum Chem. 2005, 101, 40e54. 35. Freeman, F.; Entezam, B.; Gomarooni, F.; Welch, T. S.; Shainyan, B. A. J. Organomet. Chem. 2005, 690, 4103e4113. 36. Freeman, F.; Shainyan, B. A. Int. J. Quantum Chem. 2005, 105, 313e324. 37. Shainyan, B. A. Int. J. Quantum Chem. 2007, 107, 189e199. 38. Pestunovich, V. A.; Larin, M. F.; Sorokin, M. S.; Albanov, A. I.; Voronkov, M. G. J. Organomet. Chem. 1985, 280, C17eC20. 39. Shainyan, B. A.; Suslova, E. N.; Kleinpeter, E. J. Phys. Org. Chem. 2011, 24, 698e704.  Ruff, F.; Koritsa nszky, T.; Argay, G.; K n, A. J. Mol. 40. Jalsovszky, I.; Kucsman, A.; alma Struct. 1987, 156, 165e192. 41. Kirpichenko, S. V.; Kleinpeter, E.; Ushakov, I. A.; Shainyan, B. A. J. Phys. Org. Chem. 2011, 24, 320e326. 42. Allinger, N. L.; Tribble, M. T. Tetrahedron Lett. 1971, 12, 3259e3262. 43. Hodgson, D. J.; Rychlewska, U.; Eliel, E. L.; Manoharan, M.; Knox, D. E.; Olefirowicz, E. M. J. Org. Chem. 1985, 50, 4838e4843. 44. Senderowitz, H.; Guarnieri, F.; Still, W. C. J. Am. Chem. Soc. 1995, 117, 8211e8219. 45. Wiberg, K. B.; Castejon, H.; Bailey, W. F.; Ochterski, J. J. Org. Chem. 2000, 65, 1181e1187. 46. Lambert, J. B.; Featherman, S. I. Chem. Rev. 1975, 75, 611e626.

47. Lambert, J. B.; Mixan, C. E.; Johnson, D. H. J. Am. Chem. Soc. 1973, 95, 4634e4639. 48. Lazareva, N. F.; Shainyan, B. A.; Kleinpeter, E. J. Phys. Org. Chem. 2010, 23, 84e89. 49. LeMaster, C. B.; LeMaster, C. L.; Tafazzoli, M.; Suarez, C.; True, N. S. J. Phys. Chem. 1990, 94, 3461e3466. 50. Lunazzi, L.; Casarini, D.; Cremonini, M. A.; Anderson, J. E. Tetrahedron 1991, 47, 7465e7470. 51. Shainyan, B. A.; Ushakov, I. A.; Koch, A.; Kleinpeter, E. J. Org. Chem. 2006, 71, 7638e7642. 52. Shainyan, B. A.; Ushakov, I. A.; Mescheryakov, V. I.; Schilde, U.; Koch, A.; Kleinpeter, E. Tetrahedron 2007, 63, 11828e11837. 53. Shainyan, B. A.; Ushakov, I. A.; Mescheryakov, V. I.; Koch, A.; Kleinpeter, E. Tetrahedron 2008, 64, 5379e5383. 54. Shainyan, B. A.; Suslova, E. N.; Kleinpeter, E. J. Phys. Org. Chem. 2012, 25, 83e90. 55. Tacke, R.; Heinrich, T.; Bertermann, R.; Burschka, C.; Hamacher, A.; Kassack, M. U. Organometallics 2004, 23, 4468e4477. 56. Heinrich, T.; Burschka, C.; Penka, M.; Wagner, B.; Tacke, R. J. Organomet. Chem. 2005, 690, 33e47. € nsch, B.; Tacke, R. Organometallics 2006, 57. Ilg, R.; Burschka, C.; Schepmann, D.; Wu 25, 5396e5408. 58. Tacke, R.; Nguyen, B.; Burschka, C.; Lippert, W. P.; Hamacher, A.; Urban, C.; Kassack, M. U. Organometallics 2010, 29, 1652e1660. 59. Lazareva, N. F.; Albanov, A. I.; Shainyan, B. A.; Kleinpeter, E. Tetrahedron 2012, 68, 1097e1104. 60. Shainyan, B. A.; Kirpichenko, S. V.; Shlykov, S. A.; Kleinpeter, E. J. Phys. Chem. 2012, 116, 784e789. 61. Shainyan, B. A.; Kirpichenko, S. V.; Kleinpeter, E. Arkivoc 2012, 175e185. 62. Eliel, E. L.; Kandasamy, D.; Yen, C.-Y.; Hargrave, K. D. J. Am. Chem. Soc. 1980, 102, 3698e3707. 63. Delpuech, J.-J. In Cyclic Organonitrogen Stereodynamics; Lambert, J. B., Takeuchi, Y., Eds.; VCH: New York, NY, 1992; Chapter 7, pp 169e191. 64. Shainyan, B. A.; Kirpichenko, S. V.; Kleinpeter, E.; Shlykov, S. A.; Osadchiy, D. Y.; Chipanina, N. N.; Oznobikhina, L. P. J. Org. Chem. 2013, 78, 3939e3947. 65. Shainyan, B. A.; Kirpichenko, S. V.; Kleinpeter, E. Tetrahedron 2012, 26, 7494e7501. 66. Kirpichenko, S. V.; Shainyan, B. A.; Kleinpeter, E. J. Phys. Org. Chem. 2012, 25, 1321e1327. 67. Weldon, A. J.; Tschumper, G. S. Int. J. Quantum Chem. 2007, 107, 2261e2265. 68. Bjornsson, R.; Arnason, I. Phys. Chem. Chem. Phys. 2009, 11, 8689e8697.  Jonsdottir, S.; Girichev, G. V.;  Bjornsson, R.; Kvaran, A.; 69. Wallevik, S. O.; Giricheva, N. L.; Hassler, K.; Arnason, I. J. Mol. Struct. 2010, 978, 209e219. 70. Schneider, H.-J.; Hoppen, V. J. Org. Chem. 1978, 43, 3866e3873. 71. Noll, J. E.; Daubert, B. F.; Speier, L. J. J. Am. Chem. Soc. 1951, 73, 3871e3873. 72. Sommer, L. H.; Rockett, J. J. Am. Chem. Soc. 1951, 73, 5130e5134. 73. Zingler, G.; Kelling, H.; Popowski, E. Z. Anorg. Allg. Chem. 1981, 476, 41e54. 74. Lazareva, N. F.; Shainyan, B. A.; Schilde, U.; Chipanina, N. N.; Oznobikhina, L. P.; Albanov, A. I.; Kleinpeter, E. J. Org. Chem. 2012, 77, 2382e2388. 75. Arata, Y.; Aoki, T.; Hanaoka, M.; Kamei, M. Chem. Pharm. Bull. 1975, 23, 333e339. 76. Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds; Wiley: New York, NY, 1994, 1267 pp. 77. Juaristi, E.; Ordonez, M. Tetrahedron 1994, 50, 4937e4948. 78. Oliveira, P. R.; Rittner, R. Spectrochim. Acta, Part A 2005, 62, 30e37. 79. Oliveira, P. R.; Rittner, R. Magn. Reson. Chem. 2008, 46, 250e255. 80. Eliel, E. L.; Enanoza, R. M. J. Am. Chem. Soc. 1972, 94, 8072e8081. 81. Mazaleyrat, J. P.; Welvart, Z. J. Chem. Soc., Chem. Commun. 1969, 485e486. 82. Sicsic, S.; Welvart, Z. J. Chem. Soc., Chem. Commun. 1966, 499e500. 83. Uebel, J. J.; Goodwin, H. W. J. Org. Chem. 1968, 33, 3317e3319. 84. Allinger, N. L.; Liang, C. D. J. Org. Chem. 1968, 33, 3319e3321.