Carbonyl groups Umpolung

Sigmatropic rearrangements of allyl sulphonium allyl ylides (75) provide the basis of a repetitive one-pot ring-expansion sequence" for 2-vinyl thiocyclic compounds (Scheme 50). A paper" and a section in a review article" have described the utilization of allyl thiol dianions and allyl sulphide anions in carbonyl group umpolung . 

After the umpolung of an aldehyde group by conversion to a l,3 dithian-2-ide anion (p. 17) it can be combined with a carbonyl group (D. Seebach, 1969, 1979 B.-T. GrO-bel, 1977 B). Analogous reagents are tosylmethyl isocyanide (TosMIC), which can be applied in the nucleophilic formylation of ketones (O.H. Oldenziel, 1974), and dichloromethyl lithium (G. KObrich, 1969 P. Blumbergs, 1972 H. Taguchi, 1973),... 

Acyloins (a-hydroxy ketones) are formed enzymatically by a mechanism similar to the classical benzoin condensation. The enzymes that can catalyze reactions of this type arc thiamine dependent. In this sense, the cofactor thiamine pyrophosphate may be regarded as a natural- equivalent of the cyanide catalyst needed for the umpolung step in benzoin condensations. Thus, a suitable carbonyl compound (a -synthon) reacts with thiamine pyrophosphate to form an enzyme-substrate complex that subsequently cleaves to the corresponding a-carbanion (d1-synthon). The latter adds to a carbonyl group resulting in an a-hydroxy ketone after elimination of thiamine pyrophosphate. Stereoselectivity of the addition step (i.e., addition to the Stand Re-face of the carbonyl group, respectively) is achieved by adjustment of a preferred active center conformation. A detailed discussion of the mechanisms involved in thiamine-dependent enzymes, as well as a comparison of the structural similarities, is found in references 1 -4. 

Umpolung The reversal of polarity of the carbonyl carbon atom is termed umpolung (German for polarity reversal). Normally the carbonyl carbon atom of an aldehyde (or a ketone) is partially positive i.e., electrophilic and therefore it reacts with nucleophiles. When the aldehyde is converted to a dithiane by reaction with 1,3-propanedithiol and reacted with butyl lithium the same carbon now becomes negatively charged to react with electrophiles. This reversed polarity of the carbonyl carbon is termed umpolung which increases the versatility of the carbonyl group in synthesis. The sulphur atoms stabilize... 

The term Umpolung is most often used to describe the reversal of the carbon polarity when going from a carbonyl group to the carbanion of a dithioacetal. 

These are only three of many ways that have been reported for the formation of acyl anion equivalents, which are among the most common umpolung synthons to be found in the literature. All are prepared by a similar strategy in that they contain functional groups which can sustain a negative charge on an adjacent carbon and can be converted back to a carbonyl group. 

In conctwilon, the two pathways of our umpolung method can be satisfactorily applied to the a,p ethylenic aldehydes or ketones bearing no substituent or an alkyl at the vinylic carbon p to the carbonyl group but, when an aryl group substitutes this position, only the second pathway is possible with some reactive aldehydes. 

The use of species 118 for the umpolung of a carbonyl group, the Stetter reaction, was demonstrated for the intramolecular asymmetric conjugate addition of a formyl group to the enoate moiety of 119 to give the cyclization product 120 in high ee and yield (Scheme 15) [64]. 

Interestingly, deprotection (hydrolysis) of the heterocyclic auxiliary exposes a synthetically useful carbonyl group. This is possible in our system since the auxiliary is bonded to the carbonyl group by a carbon atom rather than a heteroatom. Such hydrolyses are well established for 1,3-dithiane derivatives as a result of their ubiquity as synthons for umpolung reactivity of the carbonyl group (Fig. I).5... 

Umpolung is a general class of reactions in which the characteristic reactivity of a group or an atom is temporarily reversed. The concept of umpolung is helpful especially with carbonyl groups. But to understand this concept, it is important to understand the normal reactivity of the carbonyl group. For example, under normal conditions carbonyl carbon is electrophilic and the a-carbon is nucleophilic because of the resonance, as shown below ... 

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). 

Single electron oxidation of the non-activated carbonyl group, e.g. in aliphatic or aromatic aldehydes, ketones and carboxylic acid derivatives, is, on the other hand, much less feasible and only a handful of methods and synthetic applications are known. Useful methods for synthetic applications are chemical modifications to lower the oxidation potentials by peripheral donor substitution and a-silylation, or redox umpolung via oxidation of the corresponding carbonyl enols or enol ethers. 

Overall an inversion of polarity of the carbonyl group can thus be achieved this principle was called umpolung by Seebach. We owe to Corey and Seebach the use of the anions of dithiane, which are more stable than those of noncyclic thioacetals. Although this question was reviewed by Seebach and also by Durst in Comprehensive Organic Chemistry ," we will briefly comment on the main reactions of the dithiane group. 

Diselenoacetals are also useful for the protection or umpolung of the carbonyl group. - Bis(al-kylseleno)alkanes and arylseleno analogs are prepared by the reaction of carbonyl compounds with sele-nols and trimethylsilyl selenides in the presence of acid catalysts (cone. HCl, cone. H2SO4, Lewis acids such as BP3 Et20, TiCU, ZnCh or AICI3) or with tris(methylseleno)borane in the presence of LAH and BF3Et20.274... 

Redox condensation between two carbonyl groups by virtue of intramolecularity can be initiated by an azolecarbene. The more electrophilic formyl group that is attached to an aromatic ring undergoes umpolung by accepting the carbene/ylide then the adduct adds across a proximal carbonyl group. The use of a chiral carbene (e.g., 192) naturally empowers enan-tiomerization of the reaction. ... 

Dithiane metallate alkylation was introduced by Corey and Seebach in 1965 and has served well as a method for forging carbon-carbon bonds at a masked carbonyl group by nucleophilic displacement. The method, an example of an umpolung process, has found extensive use for advanced fragment assembly in target-directed synthesis. Contributions from the Smith research group at the University of Pennsylvania, in particular, have served to demonstrate the power of this... 

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). 

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