Ethynyl cyclohexane

The competitive experiments were carried out with a series of terminal al-kynes characterized by similar electronic properties but differing in portions of the molecule remote from the reaction site. For aliphatic alkyne, the three substrates ethynyl cyclohexane, 1-octyne (which represents an acyclic isomer of the former substrate), and 1-dodecyne were tested, with the free catalyst compared to the encapsulated catalyst. In the former case, after a short induction time, the initial reaction rate for the three substrates showed similar behavior for 1-dodecyne and 1-octyne, while the cyclic isomer, being slightly more electron rich, reacted 1.5 times faster (Fig. 7.8a). Encapsulation of the catalyst led to a magnification of the favorable hydration of the cyclic substrate that reacted more than twice as rapidly as the longer substrate. It is likely that extended linear substrates, that in their extended conformation are approximately 1.4 and 2.1 times longer than ethynyl cyclohexane, have to fold to better complement the residual space left available within Ihe cavity occupied by the catalyst. 

FIGURE 7.8 Comparison of substrate selectivity displayed by the NHC-Au(I) catalyst in the hydration reaction of alkynes free in solution and encapsulated in the hexamer (a) preferential hydration of cyclic ethynyl cyclohexane rather than acyclic aUphatic terminal alkynes and of (b) shorter rather than longer aromatic rigid alkynes. 

Interestingly, trimer was formed through secondary bonds between the iodine(III) and the two oxygen atoms (01 and 02) in the solid state of 1-alkynyl-lA3,2-benziodoxol-3(lH)-one 142 (Fig. 8) [225]. In the solid state the ethynyl substituent occupies an axial position of the cyclohexane chair conformer. 

As just mentioned, a more significant value for the anomeric effect of a polar substituent could be calculated if the A value at position 2 of oxane were known. But this can be measured only for weakly polar substituents such as methyl, hydroxymethyl, vinyl, and ethynyl, which are supposed to exhibit no anomeric effect. For such substituents, the A value at position 2 of oxane correlates fairly well with the conformational free energy in cyclohexane. 

The relationship between the size of a substituent and EjZ product ratios can be calculated from experimental values of AG° for equatorial/axial preference of substituents in cyclohexanes. This allows the EjZ ratios in Cope products to be predicted307. In the rearrangement of 13, the methyl and the ethynyl group are of similar size, and a 45 55 EjZ mixture of Cope aproducts 14 is obtained740. 

A few interesting facts have been confirmed by the calculations. For example, the ethynyl group on a cyclohexane ring prefers to be equatorial rather than axial by 0-49 kcal mole-1 [experimental (Jensen et al., 1969), 0-41 kcal mole-1 ]. 

When cyclohexane is substituted by an ethynyl group, —C=CH, the energy difference between axial and equatorial conformations is only 1.7 kj (0.41 kcal)/mol. Compare the conformational equilibrium for methylcyclohexane with that for ethynylcyclohexane and... 

Van Look et al. (1989) separated seven estrogens on 10 X 10-cm silica gel 60 plates with a mobile phase of cyclohexane-ethyl acetate-ethanol (77.5 20 2.5). The Rp values of the separated compounds were as follows ethynyles-tradiol, 0.23 estradiol, 0.18 estradiol benzoate, 0.34 estradiol valerate, 0.42 estradiol phenylpropionate, 0.40 trenbolone acetate, 0.32 and estradiol cypio-nate, 0.47. 

The list of cyclic alcohols that are substrates for enantioselective lipase-catalyzed transesterification is very long. Among these are many cyclohexane derivatives [219-226]. Scheme 48 presents only selected examples of this class of substrate. Note that the ethynyl cyclohexenol that is enzymatically [222] resolved is a chiral intermediate for the total synthesis of vitamin D. 

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