Saytzeff orientation

The amino functional group is not commonly encountered in steroid synthesis except perhaps in steroidal alkaloids. However, certain elimination reactions have been shown to have theoretical and limited preparative importance, largely due to the efforts of McKenna and co-workers. The Hofmann rule for 2 elimination predicts that alkaline elimination of quaternary ammonium salts will occur towards the carbon carrying the most hydrogen atoms cf. the converse Saytzeff orientation, above). In cyclohexyl systems, the requirement for diaxial elimination appears to be important, as in other 2 eliminations, and the Hofmann rule frequently is not obeyed [e.g., (116) (117)]. 

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 Saytzeff orientation rule (i.e., proceed toward the most substituted / carbon), as do Ex eliminations (see ref. 214). However, the best geometrical arrangement of the four centers involved in E2 eliminations is anti-coplanar and in the cyclohexane system only the trans-diaxial situation provides this. 

It has been argued that die accepted electromeric interpretation of Saytzeff orientation and its exceptions is unsound. A Unified Rule for Elimination (URE) has now been proposed to account for regioselectivity of eliminations of a wide range of substrates and reaction conditions.8... 

It has been argued that the accepted electromeric interpretation of Saytzeff orientation... 

This new use of DMSO has not only yielded information relating to the recently exposed syn-anti dichotomy (Sicher, 1972), but has also revealed new facets of the century-old Hoffmann-Saytzeff orientation controversy. 

Predominant formation of the more stable isomer is called Saytzeff orientation after the Russian chemist Alexander Saytzeff (University of Kazan), who in 1875 first formulated a rule" for orientation in dchydrohalogenation. 

Thorough mechanistic studies have established that dehydration over acidic oxides follows two major routes. A single-step, concerted E2 mechanism, usually results in alkenes with Saytzeff orientation (more substituted alkene isomers, 1) (Scheme 1). The El mechanism, in turn, is a two-step process which starts with the removal of the OH group. Because carbocationic intermediates are involved they eventually give rise to a mixture of isomeric alkenes (1-4). A third route of lesser significance (ElcB mechanism), initiated by the removal of a proton from the P carbon, occurs characteristically on basic oxides. In this route the Hofmann orientation (formation of the less substituted alkene, 2) usually prevails. 

When used for the dehydration of alcohols most acidic oxides result in the formation of alkenes with Saytzeff orientation, i.e. an E2 mechanism is operative. This means that secondary 2-alkanols are transformed to 2-alkenes. A characteristic catalyst achieving such selectivity is alumina treated with alkali metal cations, ammonia, or organic bases [2], Such treatment is necessary because pure, strongly acidic alumina induces skeletal rearrangements and double bond migration. The importance of choosing a catalyst with the appropriate characteristics is illustrated in Scheme 2 [17,18]. 

Previous results [4-8] for the same reaction on zirconia-, ceria-, and lanthana-based catalysts showed a correlation between the acid-base properties (in terms of both the concentration and the strength of the sites) of the samples and their catalytic behaviour. When the number of the acid sites is sensibly higher than that of the basic ones, the main product is the undesired 2-alkene, which forms through an El mechanism (Saytzeff orientation). The alcohol adsorbs on the oxide surface through the interaction between the OH group and an acid site the rupture of the C-OH bond leads to the carbocation which mainly gives the... 

Reaction coordinate diagram for dehydrobromination of 2-bromo-butane to 1-butene and 2-butene with Saytzeff orientation. 

Dehydrobromination of 2-bromo-2,4,4-trimethylpentane (78) with 4.0M KOH in ethanol at 70°C produces 86% of 2,4,4-trimethyl-l-pentene (79) cind 14% of 2,4,4-trimethyl-2-pentene (80). The heat of hydrogenation of 79 is —25.52 kcal/mol, while that of 80 is —26.79 kcal/mol. Is this dehydrobromination an example of Saytzeff orientation or Hofmann orientation ... 

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