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A similar finding about the effect of substituents on rotational barriers was found by Kelly and co-workers in their research on molecular ratchets increasing the size of the "pawl" of a ratchet lowered the barrier to rotation. Their explanation for this observation is that a larger pawl increases the energy of the ground state of the molecule, thus bringing it closer to the rotation energy barrier. See: Kelly, T. R.; Sestelo, J. P.; Tellitu, I. J. Org. Chem. 1998, 63, 3655-3665.
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While this paper was under consideration, Tietze et al. published an attractive asymmetric catalytic synthesis of chiral overcrowded alkenes that are structurally analogous to second-generation molecular motors. See: Tietze, L. F, Düfert, A, Lotz, F, Sölter, L, Oum, K, Lenzer, T, Beck, T, Herbst-Irmer, R. J. Am. Chem. Soc. 2009, 131, 17879-17884
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While this paper was under consideration, Tietze et al. published an attractive asymmetric catalytic synthesis of chiral overcrowded alkenes that are structurally analogous to second-generation molecular motors. See: Tietze, L. F.; Düfert, A.; Lotz, F.; Sölter, L.; Oum, K.; Lenzer, T.; Beck, T.; Herbst-Irmer, R. J. Am. Chem. Soc. 2009, 131, 17879-17884.
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29 The absolute configuration of ketone 10 (as well as that of the successive compounds ketone 4, TBDMS hydrazone 11, and alkenes 5, 6, and 7) was confirmed by X-ray crystallography with refinement of the Flack parameter of alkene 5.
-
29 The absolute configuration of ketone 10 (as well as that of the successive compounds ketone 4, TBDMS hydrazone 11, and alkenes 5, 6, and 7) was confirmed by X-ray crystallography with refinement of the Flack parameter of alkene 5.
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75749113464
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The presented procedure does not provide bis-TBDMS hydrazine in a yield better than the procedure of Furrow and Myers,26 as the formation of bis-TBDMS hydrazine under the described conditions only goes to 80% completion, and at least two distillations are needed to obtain pure bis-TBDMS hydrazine. The presented procedure, however, does not involve the heating of anhydrous hydrazine. Therefore, it can be regarded as a safer alternative, more suitable for the large-scale preparation of bis-TBDMS hydrazine in a laboratory environment
-
26 as the formation of bis-TBDMS hydrazine under the described conditions only goes to 80% completion, and at least two distillations are needed to obtain pure bis-TBDMS hydrazine. The presented procedure, however, does not involve the heating of anhydrous hydrazine. Therefore, it can be regarded as a safer alternative, more suitable for the large-scale preparation of bis-TBDMS hydrazine in a laboratory environment.
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52
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75749123625
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Although the presented procedure avoids the use of anhydrous hydrazine, suitable safety precautions should still be taken. It is strongly recommended to perform the preparation of bis-TBDMShydrazine behind a safety blast shield
-
Caution: Although the presented procedure avoids the use of anhydrous hydrazine, suitable safety precautions should still be taken. It is strongly recommended to perform the preparation of bis-TBDMShydrazine behind a safety blast shield.
-
Caution
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53
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Furrow and Myers screened a broad range of different Lewis acid catalysts and found Sc(OTf)3 to be the most effective; see ref 26
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3 to be the most effective; see ref 26.
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54
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Furrow and Myers have successfully employed diethyl ether as a cosolvent in some of their reactions to prepare TBDMS-protected hydrazone derivatives
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Furrow and Myers have successfully employed diethyl ether as a cosolvent in some of their reactions to prepare TBDMS-protected hydrazone derivatives.
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55
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We were not able to find conditions for the separation of (S)-5 and triphenylphosphine sulfide with regular silica gel or aluminum oxide.
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We believe that the observed higher stability with TLC silica gel (Analtech UNIPLATE, 2000 μm) could be the result of its higher degree of purity, which would cause it to contain less acidic impurities than silica gel used for column chromatography SiliCycle SiliaFlash P60, 40-63 μm
-
We believe that the observed higher stability with TLC silica gel (Analtech UNIPLATE, 2000 μm) could be the result of its higher degree of purity, which would cause it to contain less acidic impurities than silica gel used for column chromatography (SiliCycle SiliaFlash P60, 40-63 μm).
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75749115311
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The small absorption observed at 4.10 ppm originates from a trace amount of dichloromethane
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The small absorption observed at 4.10 ppm originates from a trace amount of dichloromethane.
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61
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75749155991
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In addition, a 2D NOESY spectrum of (S, M)-7 was recorded, which can be found in the Supporting Information
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In addition, a 2D NOESY spectrum of (S)-(M)-7 was recorded, which can be found in the Supporting Information.
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1H NMR spectra can be found in the Supporting Information.
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1H NMR spectra can be found in the Supporting Information.
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67
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75749096416
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1H NMR, that prolonged concentrating in vacuo at this temperature would lead to partial deprotection of the hydrazone; however, this partial deprotection did not result in lower ee's or yields.
-
1H NMR, that prolonged concentrating in vacuo at this temperature would lead to partial deprotection of the hydrazone; however, this partial deprotection did not result in lower ee's or yields.
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