Corey-Seebach

In an extension of the procedure, thiols react with gem-dihaloalkanes (Table 4.4) to produce thioacetals [ 10,20-23] and the reaction can be employed in the Corey-Seebach synthesis of aldehydes and ketones (see ref. 24 and references cited therein), gem-Dichlorocyclopiopanes having an electron-withdrawing group at the 2-position react with thiols to produce the thioacetals [25]. In the corresponding reaction of the thiols with biomochloromethane exclusive nucleophilic substitution of the bromo group by the thiolate anion occurs to yield the chloromethyl thioethers [13, 14] (Table 4.5). 

For a long list of synthons for RCO, with references, see Hase Koskimies Aidrichimica Acta 1982, 15. 35-41. For example, see Corey Seebach, Ref. 1501 Jones Grayshan Chem. Commun. 1970, 141, 741. 

If the reaction is carried out on dithioesters, carbanions stabilized by two a-sulfur atoms are formed. Such carbanions are analogous to those obtained by deprotonation of dithioacetals, such as Corey-Seebach... 

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. 

Regiocontrolled Corey-Seebach s epoxide ring-opening with 1,3-dithianyl anion... 

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... 

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). 

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