Seebach reaction

Dithiane as a nucleophile, serving as a masked carbonyl equivalent. This is an example of umpolung. 

Example 3, Ethyl is infinitely different from methyl  

Name Reactions A Collection of Detailed Mechanisms and Synthetic Applications, DOI 10.1007/978-3-319-03979-4 74, Springer International Publishing Switzerland 2014 

Name Reactions, 4th ed., DOI 10.1007/978-3-642-01053-8 67, Springer-Verlag Berlin Heidelberg 2009 

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The Corey-Seebach Reaction (or Seebach Umpolung) uses lithiated 1,3-dithianes as nucleophilic acylating agents. 

The Corey-Seebach Reaction allows a reversal of the normal reactivity of acyl carbon atoms, which combine only with nucleophiles. The German term Umpolung is widely used for this inversion of reactivity. 

Scheme 1.3 Conversion of hexanal into dipentyl ketone (corey-seebach reaction)...

In Scheme 1.3, hexanal on reaction with 1,3-propanedithiol gives the 1,3-dithiane derivative 1.8. A strong base such as u-butyllithium abstracts the proton to give the corresponding 2-lithio-1,3-dithiane 1.9, which reacts with 1-bromopentane to give alkylated product 1.10. Treatment of 1.10 with FIgO and BF3 (boron trifluoride) in aqueous THF (tetrahydrofuran) yields the dipentyl ketone (the corey-seebach reaction ). Thus, dithianyllithium (2-lithio-1,3-dithiane) 1.9 is an acyl anion synthetic equivalent. 

The only example of the equivalent of a Corey-Seebach reaction of the lithium derivative of a carbonyl-protected aldehyde involves an acetylenic ketone (equation 6-25).61... 

An attempt to accomplish asymmetric induction using a dialkoxyboryl enolate has been made by Chow and Seebach. Reaction of the alkenyloxydialkoxyborane (122) derived from (-)-(S)-l,l -bi-2-... 

In 1971 we discovered ( ) that the reaction of conforma-tionally locked 2-dithianyllithium compounds with electrophiles (Corey-Seebach reaction) proceeds with remarkable stereoselectivity, giving virtually exclusively the equatorial substitution products, as exemplified in Scheme 1 (R=H). The preference for the l,3-dithicUiyl-2-carbcUiion to undergo electrophilic siibstitu-tion from the equatorial side amoiints to over 6 kcal/mol ( ), corresponding to a selectivity factor in excess of 10,000. This high preference was subsequently shown to be due to stereo-electronic factors, in accord with theoretical predictions (4, 5, 6). 

An interesting example of the a-alkylation of a-amino acids without loss of optical activity has been reported by Seebach. Reaction of proline with pivalde-hyde gave the single stereoisomer 60 (1.75). Deprotonation with LDA to the chiral non-racemic enolate and addition of an electrophile, such as iodomethane, gives... 

The above two-step reaction sequence is of unusual interest from a synthetic perspective. Note that we have converted a typically electrophilic aldehyde (carbonyl) carbon into a nucleophilic carbanion center in the 1,3-dithiane anion. The overall process thus accomplishes a polarity inversion or, to use the more popular German term, umpolung. The 1,3-dithiane anion may now be reacted with a variety of electrophiles, such as alkyl halides, epoxides, and carbonyl compounds, in what is known as the Corey-Seebach reaction ... 

Dithiolanes, however, are rarely used in the Corey-Seebach reaction because anions derived from them undergo fragmentation via a pericyclic pathway, producing ethylene as one of the products. Use arrow pushing to explain this process. 

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