Dithianes anions, reaction with carbonyls

When deprotonation is effected in a 2-allyl-1,3-oxathiane with 5cc-butyllithium, the expected allylic anion is generated. Interestingly, reaction with alkyl halides leads to substitution at the a-terminus (52), whereas reaction with carbonyl compounds gives products of substitution at the y-terminus (53) (Scheme 18) <92TL250l>. In contrast, when the anion derived from 2-allyl-1,3-dithiane... 

Halo-1,3-dithiane trans-l,3-dioxides (80 X = Cl, Br) act as diastereoselective carbonyl anion equivalents in reactions with aldehydes.117 The scope of the reaction has been explored by varying the temperature, the aldehyde, and the metal used as counterion. Similarly, metal 1,3-dithianides (81 M = Li, Cu1) can be added diastereoselec-tively to chiral aldehydes subsequent hydrolysis yields an a-hydroxyaldehydc.118... 

The scope and limitations of the metal anions of 2-halo-l,3-dithiane trans-1,3-dioxide as diastereoselective carbonyl anion equivalents has been explored with regard to reaction with aldehydes.79 Reactions of metallated trans-, 3-dithiolanc 1,3-dioxide (five-membered ring) with aldehydes under kinetic and thermodynamic control have also been studied and contrasted with those of the metallated monooxide, parent sulfide, and 1,3-dithiane 1,3-dioxide (six-membered ring).80... 

The hydrogen on the carbon attached to the two sulfur atoms is weakly acidic (pAf, = 31) and can be removed by reaction with a strong base, such as butyllithium. (Butyl-lithium is also a nucleophile, and therefore it is not used to generate enolate anions from carbonyl compounds. However, the dithiane is not electrophilic, so butyllithium can be used as the base in this reaction.)... 

The dithiane anion 1.9 also reacts with acyl halides, ketones and aldehydes to give the corresponding dioxygenated compounds. Schemes 1.4 and 1.5 show the reaction of dithiane anions 1.11 and 1.12 with ketones. The most common example of umpolung reactivity of a carbonyl group is the benzoin condensation (Scheme 1.6). 

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 ... 

The first step in the synthesis is an oxidation of the alcohol starting material (via PCC or Swern conditions) to give the needed carbonyl. Reaction of this ketone with the 1,3-dithiane anion shown, followed by hydrolysis, affords the desired TM. 

Micalizio and coworker reported a three-component coupling sequence for the synthesis of substituted pyridines in 2012 [121]. The reaction proceeded through nucleophilic addition of a dithiane anion to an Q ,/3-unsaturated carbonyl followed by metallacycle-mediated union of the resulting allylic alcohol with preformed trimethylsilane-imines (generated in situ by the low temperature reaction of lithium hexamethyldi-silazide with an aldehyde) and Ag(I)- or Hg(II)-mediated ring closure. Good yields of substituted pyridines were isolated. 

The anion 117 prepared by deprotonation of the carbene complex [Cr(CO)s C(OEt)CH2CHS(CH2)3S ] (116) also rearranges spontaneously by carbonyl insertion to give a neutral six-membered chelate (118) after alkylation. The analogous tungsten carbene complex affords stereoselec-tively a vinylcarbene complex (119) by opening of the 1,3-dithiane ring (705). Reaction of 118 with methyl hydrazine produces mainly an NMe- or... 

Review. Seebach and Corey have published a general paper on the preparation and metalation of 1,3-dithianes and examples of the reaction of 2-lithio-l,3-dithianes with electrophilic reagents (alkyl halides, carbonyl compounds, acids, and oxides). The value of these sulfur-stabilized anionic reagents is that they are equivalent to acyl anions (a), in which the normal polarity of the carbonyl group is reversed (reversible umpolung). 

The anions, generated in situ by desilylation of silylacetylenes, allylsilanes, propargylsilanes, a-silyloxetanones, bis(trimethylsilylmethyl) sulfides, and other silane derivatives,can undergo nucleophilic addition to ketones and aldehydes (eq 11). Al-(C,C-bis(trimethylsilyl)methyl) amido derivatives can add to aldehydes followed by Peterson alkenation to form acyl enamines. Treatment of 2-trimethylsilyl-l,3-dithianes can generate dithianyl anions, which are capable of carbocyclization via direct addition to carbonyl or Michael addition (eq 12). The fluoride-catalyzed Michael additions are more general than Lewis acid-catalyzed reactions and proceed well even for those compounds with enolizable protons and/or severe steric hindrance (eq 13). ... 

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