Patai S., Rappoport Z. 1997 The chemistry of functional groups. The chemistry of double-bonded functional groups / 1281 135

22. Radical anions and cations derived from CDC, CDO or CDN groups 1311

synthetic utility of this chemistry (Scheme 30). Electrophiles such as cyclohexanone, benzaldehyde, diphenyldisulfide and carbon dioxide successfully reacted in yields of 65 80%. In sense, this technique is superior to the related cyclizations of the 5-hexenyl radical involving n-Bu3SnH in that there is no loss of functionality at the radical center after cyclization.

HO CH3

O

HMPA

A similar cyclization of a ketyl anion (produced via reaction with Sml2) onto an allene was reported by Gillmann in 1993 (equation 29)85 The regiochemistry and high diasteroselectivity associated with this process was explained on the basis of a ‘chelation-controlled’ cyclization (e.g. TS 48). The same reduction carried out with n-Bu3SnH resulted in only a 37% yield and a 5 : 1 ratio of diastereomers.

Analogous intramolecular ‘chelation-controlled’ ketone/olefin couplings with Sml2, in which SmC3 was complexed in a cyclic manner to the ketyl anion and a ˇ-carbonyl of an ester or amide functionalilty, were reported as early as 1987 (Scheme 31)86. The cyclized samarium intermediate 49 could be further reacted with added electrophiles such as aldehydes or ketones87.

Cyclization of ketyl anions onto allyl sulfides or sulfones were reported to yield 2- vinylcyclopentananols according to equation 3088.

X

X = SPh (50%)

X = SO2 Ph (80%)

22. Radical anions and cations derived from CDC, CDO or CDN groups 1313

The effect of the counterion on the outcome of this reaction was attributed to ion-pairing effects (Scheme 32). It was suggested that the ketyl anion 52 is more easily reduced when LiC is the counterion, and that this second reduction occurs faster than cyclization90.

O−M+

−

51

SCHEME 32

Intramolecular cyclizations of ketyl anions (generated electrochemically at a Sn cathode in isopropanol) onto a remote C N were reported in 199291. ˛-Hydroxyketones are produced in yields ranging from 60 80%, depending on the structure of the substrate (Scheme 33).

SCHEME 33

(equation 32)92. Yields were low (30 50%) for unactivated alkynes (Y D H or CH3), but improved to 50 75% when Y D Si CH3 3, Ph or CO2Et. Also, yields were typically much better for ketones than for aldehydes.

C X −C C

O

FIGURE 4. Resonance forms of ˛,ˇ-unsaturated carbonyl compounds

O O

CH2 OTs

SCHEME 34

22. Radical anions and cations derived from CDC, CDO or CDN groups 1315

f. Radical anions generated from ˛,ˇ-unsaturated carbonyl compounds. The principles underlying the chemistry of radical anions generated from ˛,ˇ-unsaturated carbonyl compounds (mainly aldehydes, ketones and esters) are similar to those discussed earlier for >CDOž in general. The key difference is that, as a result of the transfer of spinand/or electron-density to the ˇ-carbon through resonance (Figure 4), new reaction pathways become accessible. There are examples in which the ˇ-carbon seems to be reacting both as a nucleophile and as a radical, several of which are discussed below.

(i) ‘Nucleophilic’ reactions of >CDC CDOž . In 1981, Gassman reported that electrochemical reductions of enones possessing a good leaving group at the υ position yield cyclopropanes in excellent (>80%) yields93. The mechanism suggested for this process is summarized in Scheme 34. (Similar reductions were achieved in the 1960s by Stork using Li/NH3, although in much lower yields.)94

In contrast, under conditions of photoinduced electron transfer, Givens and Atwater found that the major product of the reaction is C X reduced product 53 (equation 33)95. It was proposed that under these conditions, the cyclopropylcarbinyl radical 55 undergoes further (reversible) ring opening (55 ! 56, Scheme 35). The reversibility of this ring opening was demonstrated by generating radicals 55 and 56 independently via reaction of the corresponding alkyl bromides with n-Bu3Snž.

X

SCHEME 35

Little’s group has reported electroreductive cyclizations involving ˛,ˇ-unsaturated esters (equation 34)96. Based upon CV measurements, the conjugated ester rather than the aldehyde or ketone is suggested to be the electron acceptor. Although direct cyclization of

radical anion 58 was suggested initially, a more detailed mechanistic study suggests that cyclization actually occurs via anion 59 (Scheme 36)97.

The preparation of three-, fiveand six-membered rings in modest yield by the electrochemically induced coupling of activated olefins with dihalides has been reported (equation 35)98. Use of an aluminum anode was critical for the formation of cyclized product. Application of this technique to the preparation of four-membered rings was unsuccessful.

22. Radical anions and cations derived from CDC, CDO or CDN groups 1317

(ii) ‘Radical’ reactions of >CDC CDOž . In a series of papers, Mariano reported numerous examples of photochemically-induced interand intramolecular coupling reactions of enones with amines99. These reactions proceed via PIET (Scheme 37) to generate the radical anion/radical cation pair 60. Loss of ‘ZC ’ from the amminium radical cation followed by radical anion/radical coupling leads to the final adduct. An excellent review of this chemistry has recently appeared100.

SCHEME 37

Enholm has reported tandem cyclizations induced by R3SnH (Scheme 38)101. The initial cyclization is a 5-hexenyl-type cyclization of the initially formed radical anion (61 ! 62). After hydrogen transfer from R3SnH, the resulting tin enolate 63 undergoes nucleophilic addition to the nitrile.

(iii) Miscellaneous ketone (aldehyde)/activated olefin couplings. SmI2-promoted coupling of aldehydes or ketones with ˛,ˇ-unsaturated ketones, esters and nitriles have been reported (equation 36). These reactions have been suggested to involve the addition of >CDOž to the activated alkene102, although the inverse (>CDC CDXž C >CDO

!) seems more likely since activated alkenes are more easily reduced than simple aldehydes and ketones. This coupling reaction can also be promoted by Mg in CH3OH103, although mechanistically this is more complicated because the sequence of proton vs

R3 Sn

SCHEME 38

electron transfers is less clear.

X

Y

IV. RADICAL IONS OF >C=C< CONTAINING COMPOUNDS

A. Chemistry of Radical Cations Derived from Carbon Carbon Double Bonds

As will become evident in this section, in the net transformation from reactant ! product transformations many of the synthetically useful reactions involving >CDC<žC are analogous to those involving neutral, un-ionized carbon carbon double bonds (e.g. the Diels-Alder reaction, oxidation/reduction reactions, nucleophilic addition etc.). However, many of the reactions involving a neutral >CDC< often require the presence of an activating substituent in order to make the alkene more electron-deficient. In a sense, one-electron oxidation of an alkene to its radical cation provides a simple and unique mechanism for increasing the electrophilic (and, of course, radical) properties of