Fiirst Plattner-rule

Nucleophilic attack on oxirane carbon usually proceeds with inversion of configuration (Scheme 44) as expected for Sn2 reactions, even under acid conditions (Scheme 45). Scheme 45 also illustrates the fact that cyclohexene oxides open in a fran5-diaxial manner this is known as the Fiirst-Plattner rule (49HCA275) and there are very few exceptions to it. 

D-allopyranoside (421) was treated similarly (KHFj, ethylene glycol, 160°, 4 h), the 3-fluoro-D- /wco derivative 422 (42%) was obtained mainly, contrary to the Fiirst-Plattner rule, together with the 2-deoxy-2-fluoro-D-a/rro derivative 423 (17%). 

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 concept serves to rationalize most of the observed reactions of aldose oxiranes, and, in the following discussion, attention will be focused on the apparent exceptions to the Fiirst-Plattner rule. 

The reaction with A -bromosuccinimide or Af-bromoacetamide with or without added acid, on the other hand, leads predominantly to the same epoxide trans-6 as formed in the reaction with peracids. It is proposed that in the formation of cis-6 with acetyl hypobromite, hypobromous acid or A -chlorosuccinimide, nucleophilic attack of the halonium ion is fast. The epoxide ratio therefore is governed by the kinetically favored tran.v-halohydrin. However, in the reaction with A -bromosuccinimide or A -bromoacetamide the nucleophilic attack on the bromonium ion species becomes rate determining, attack of the nucleophile therefore follows the path of lowest activation energy. This is the attack on the c/.v-bromonium ion distant to the bulky tert-butyl group leading to the trans-diaxial bromohydrin, according to the Fiirst-Plattner rule, hence giving trans-6. 

FIGURE 6.9 For pyranose sugars, the Fiirst-Plattner rule predicts tran -diaxial relationships between nucleophiles and liberated hydroxyl groups. 

SCHEME 6.28 Sodium azide opens epoxides according to the Fiirst-Plattner rule. 

SCHEME 6.73 Lithium aluminum hydride reduces epoxides producing products consistent with the Fiirst-Plattner rule. 

Another example from the macrolide field is the synthesis of antimycin A3, which starts with opening of epoxide 9 [28]. Opening of this manno epoxide with butylmagnesium chloride afforded the C3 branched-derivative 10 with total regio- and stereo-selectivity. Again the Fiirst-Plattner rule applies and the introduction of the substituent at C3 was expected. The remainder of the synthesis... 

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