Trans-diaxial

It has generally been assumed that phosphorous oxychloride-pyridine dehydrations, the elimination of sulfonates, and other base catalyzed eliminations (see below) proceed by an E2 mechanism (see e.g. ref. 214, 215, 216). Concerted base catalyzed eliminations in acyclic systems follow the Saytzelf orientation rule i.e., proceed toward the most substituted carbon), as do eliminations (see ref 214). However, the best geometrical arrangement of the four centers involved in 2 eliminations is anti-coplanar and in the cyclohexane system only the tran -diaxial situation provides this. 

Thionyl chloride behaves in some circumstances as though it dehydrates by tran -diaxial elimination, as described for phosphorous oxychloride. For example, the 5a-alcohol (102) undergoes anti-Saytzelf elimination to give the A" -olefin. In this particular example, phosphorous oxychloride-pyridine does not work, and acetic anhydride-sulfuric acid gives the A -isomer (ref. 185, p. 199). 

The stereochemistry of formation and rearrangement of vicinal dihaUdes has been elucidated, chiefly by Barton s group. Trans diaxial addition occurs but the product may then equilibrate with the more stable... 

The acetates of vicinal diols undergo reductive elimination on treatment with metal-ammonia yields of olefin are only significant if one ester is tertiary and the arrangement is tran -diaxial. ... 

The anti periplanar requirement for E2 reactions overrides Zaitsev s rule and can be met in cyclohexanes only if the hydrogen and the leaving group are trans diaxial (Figure 11.19). If either the leaving group or the hydrogen is equatorial, E2 elimination can t occur. 

The elimination of HC1 from the isomeric menthyl and neomenthyl chlorides shown in Figure 11.20 gives a good illustration of this trans-diaxial requirement. Neomenthyl chloride undergoes elimination of HC1 on reaction with ethoxide ion 200 times as fast as menthyl chloride. Furthermore, neomenthyl chloride yields 3-menthene as the major alkene product, whereas menthyl chloride yields 2-nienthene. 

Attack by iodine and COgH on the double bond of (30) must be trans, hence I is axial in (29) and elimination to (28) is easy. Epoxidatlon occurs on the less hindered side of the double bond to give (27) which is opened by bromide to trans diaxial (26). This compound was protected as a silyl ether. 

The marked ANTI stereoselectivity observed with cyclohexyl systems (see above) reflects the ability to achieve, and the very marked preference to eliminate from, the so-called trans-diaxial conformation (34) ... 

Thus of the geometrical isomers of hexachlorocyclohexane, C6H6C16, one is found to undergo elimination of HC1 at a rate slower, by a factor of 7-24 x 103, than any of the others it is found to be the one (35) that cannot assume the above trans-diaxial conformation. 

The relative configurations and predominant conformations of [l,2,3]oxathiazino[4,3- ]isoquinoline derivatives 177-182 were studied by means of H and 13C NMR spectroscopy with the applications of DNOE, 2D HSC, and 2D-COSY measurements. Their stereostructure includes an equilibrium between the conformers cis-1, trans and cis-2. In the /ra -structure, the B/C rings are trans-ane-WatcA with H-l lb and the N-5 lone electron pair trans-diaxial. In the cis structures, the hetero-rings are air-anellated in the cis-1 conformation C-l is in inside position, while in cis-2... 

One of the methods by which replacement of secondary hydroxyl groups by fluorine in pentofuranoses and pento- and hexo-pyranoses has been achieved is by cleavage of epoxide rings with fluoride ion. The epoxide rings are always cleaved trans-diaxially, according to the Fiirst-Plattner rule. 

The case is interesting in 1,2 dibromocyclohexane. The moment for the diaxial isomer is assumed to be zero, while the calculated and observed values for the diequatorial form are respectively 3.09 D and 3.12 D. The trans diaxial form is more stable than the trans diequatorial, although the latter is favoured sterically. The reason for the lesser stability of the trans diequatorial form is that it is destabilized by dipole repulsion. 

The opening of the epoxide in the cij-decalin 24 by acetic acid leads exclusively to the hydroxyacetate 25 (through a kinetically controlled rrani-diaxial opening) rather than to the wanted diastereomer 26 (c/ the stereochemistry of the "southern" part of reserpine). To obtain the correct diastereomer the epoxy-lactone 22 is first formed (Scheme 8.6). Thus the conformation of the cij-decalin system, and therefore that of the substituents, is reversed. The kinetic tran -diaxial opening of the epoxide occurs in a regio- and stereoselective manner to afford compound 28 in which the substituents have the correct position and configuration (a-OH, P-OAc),... 

A similar reaction pathway was found for the Sn2 substitution of an epoxide with a lithium cuprate cluster [124]. In contrast to that in the MeBr reaction, the stereochemistry of the electrophilic carbon center is already inverted in the transition state, providing the reason for the preferred trans-diaxial epoxide-opening widely observed in synthetic studies. The TS for the Sn2 reaction of cyclohexene oxide is shown in Eq. 10.12. 

In cyclic systems, the usual simple requirements of Saytzev or Hofmann rules may be overridden by other special requirements of the system, e.g. the preference for elimination from the trans-diaxial conformation in cyclohexane derivatives (c/. p. 255). Another such limitation is that it is not normally possible to effect an elimination so as to introduce a double bond on a bridgehead carbon atom in a fused ring system (Bredt s rule), e.g. (47)- (48) ... 

Working on modifications of trehalose, Richardson (with P.A. Monroe and Les Hough) demonstrated the selective tosylation at 0-2 of 4.6.4. 6 -di-(9-benzylidene-a,a-trehalose to afford a symmetrical 2,2 -ditosylate, which could be converted into the bis-manno-epoxide by the action of base (Scheme 24). The latter underwent trans-diaxial ring-opening with nucleophiles at C-3 and C-3, and many synthetic applications of this intermediate have now been recorded. One of these is shown in Scheme 24, from the Richardson-Hough laboratory, performed by postdoctoral fellow, Edward Tarelli, who contributed voluminously with Richardson to the exploration and development of trehalose chemistry. 

These reactions are examples of the preferred trans-diaxial opening of epoxides and the analogous trans-diaxial addition to double bonds. 

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