The Cram’s rule of asymmetric induction<\/strong> developed by Donald J. Cram<\/a> in 1952,\u00a0<\/span>\u00a0is an early concept relating to the prediction of stereochemistry in certain acyclic<\/a> systems. In full the rule is:<\/p>\n

In certain non-catalytic reactions that diastereomer will predominate, which could be formed by the approach of the entering group from the least hindered side when the rotational conformation of the C-C bond is such that the double bond is flanked by the two least bulky groups attached to the adjacent asymmetric center.<\/em><\/p>\n

The rule indicates that the presence of an asymmetric center in a molecule induces the formation of an asymmetric center adjacent to it based on steric hindrance<\/a>.<\/p>\n

In his 1952 publication Cram presented a large number of reactions described in the literature for which the conformation of the reaction products could be explained based on this rule and he also described an elaborate experiment (scheme 1<\/em>) making his case.<\/p>\n

\n

<\/a><\/dd>\n<\/dl>\n

The experiments involved two reactions. In experiment one 2-phenylpropionaldehyde<\/em> (1<\/strong>, racemic<\/a> but (R)-enantiomer shown) was reacted with the Grignard reagent<\/a> of bromobenzene<\/a> to 1,2-diphenyl-1-propanol<\/em> (2<\/strong>) as a mixture of diastereomers<\/a>, predominantly the threo<\/a> isomer<\/a> (see for explanation the Fischer projection<\/a>).<\/p>\n

The preference for the formation of the threo isomer can be explained by the rule stated above by having the active nucleophile<\/a> in this reaction attacking the carbonyl group<\/a> from the least hindered side (see Newman projection<\/a> A<\/strong>) when the carbonyl is positioned in a staggered<\/a> formation with the methyl<\/a> group and the hydrogen<\/a> atom, which are the two smallest substituents<\/a> creating a minimum of steric hindrance<\/a>, in a gauche orientation<\/a> and phenyl<\/a> as the most bulky group in the anti conformation<\/a>.<\/p>\n

The second reaction is the organic reduction<\/a> of 1,2-diphenyl-1-propanone<\/em> 2<\/strong> with lithium aluminium hydride<\/a>, which results in the same reaction product as above but now with preference for the erythro<\/a> isomer (2a<\/strong>). Now a hydride<\/a> anion (H^{–<\/sup>) is the nucleophile attacking from the least hindered side (imagine hydrogen entering from the paper plane).<\/p>\n}

^<\/a><\/strong> Studies in Stereochemistry. X. The Rule of “Steric Control of Asymmetric Induction” in the Syntheses of Acyclic Systems<\/em> Donald J. Cram<\/a>, Fathy Ahmed Abd Elhafez J. Am. Chem. Soc.<\/a>; 1952<\/strong>; 74(23); 5828\u20135835. Abstract<\/a><\/p>\n

 <\/p>\n","protected":false},"excerpt":{"rendered":"

The Cram’s rule of asymmetric induction developed by Donald J. Cram in 1952,\u00a0\u00a0is an early concept relating to the prediction of stereochemistry in certain acyclic systems. In full the rule is: In certain non-catalytic reactions that diastereomer will predominate, which could be formed by the approach of the entering group from the least hindered side… Continue reading Cram’s rule<\/span><\/a><\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[3,1],"tags":[8,143],"_links":{"self":[{"href":"https:\/\/amcrasto.theeurekamoments.com\/wp-json\/wp\/v2\/posts\/123"}],"collection":[{"href":"https:\/\/amcrasto.theeurekamoments.com\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/amcrasto.theeurekamoments.com\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/amcrasto.theeurekamoments.com\/wp-json\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"https:\/\/amcrasto.theeurekamoments.com\/wp-json\/wp\/v2\/comments?post=123"}],"version-history":[{"count":3,"href":"https:\/\/amcrasto.theeurekamoments.com\/wp-json\/wp\/v2\/posts\/123\/revisions"}],"predecessor-version":[{"id":126,"href":"https:\/\/amcrasto.theeurekamoments.com\/wp-json\/wp\/v2\/posts\/123\/revisions\/126"}],"wp:attachment":[{"href":"https:\/\/amcrasto.theeurekamoments.com\/wp-json\/wp\/v2\/media?parent=123"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/amcrasto.theeurekamoments.com\/wp-json\/wp\/v2\/categories?post=123"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/amcrasto.theeurekamoments.com\/wp-json\/wp\/v2\/tags?post=123"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}