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 1331

porphyrins145, and a recent report in which hexamethyl Dewar-benzene was used as a radical scavenger in epoxidations catalyzed by c-P450 itself showed no trace of radical products146.

(iv) Cyclopropanations of alkenes. ‘Hole-catalyzed’ cyclopropanation provides a useful means of adding a carbene equivalent to electron-rich alkenes under mild conditions. It has been established that the aminium-catalyzed reaction has a radical cation chain mechanism (Scheme 55)147, and that the reaction does not proceed via the relatively unreactive diazomethane radical cation148, since ethyl diazoacetate does not decompose in the presence of aminium salt and nonionizable alkenes116.

b. Oxidation/reduction of alkenes. (i) Hydrogenation. ‘Hole-catalyzed’ hydrogenation reactions were first reported in 1992, and follow a radical mechanism which destroys the triarylaminium cation radical, at a stoichiometric ratio of two moles of aminium to one of alkene (Scheme 56)149. These reactions, though limited to easily-ionizable double bonds, are quite useful as they allow the selective reduction of the more easily-ionized double bond of a polyfunctional molecule in very high yield (Scheme 57)150.

(ii) Oxygenation. The general form of this reaction involves the cleavage of a radical cation generated from an electron-rich alkene to give a benzophenone (from 1,1- diarylethylenes) or a benzaldehyde (from stilbenes). It is generally accepted that it proceeds via peroxy species, as shown in Scheme 58151.

Ph

O

O

O

O

+

O2

+

+e−

R

R′

Ph

R R′

Ph

R R′

R = Ph, R′ = H or R = H, R′ = Ph

O

O

+

Ph

R R′

H

SCHEME 58

However, it has been recently suggested that oxirane intermediates also play a part in this reaction, producing some of the minor products (Scheme 59)152. Dienes do not appear to be good substrates for this reaction, at least not with triplet oxygen, as the cation-radical ‘Diels-Alder’ dimerization is much faster unless the alkene is sterically hindered153.

Several electron acceptors have been used for this reaction, the most interesting of which are silica gel and other chromatographic supports as PIET acceptors in an efficient, solventfree reaction (Scheme 60)154. These oxygenations are carried out with 2% substrate by weight adsorbed onto silica gel, acidic alumina or Fluorisil. These reactions work quite well when the resulting powder is agitated in air under an ordinary fluorescent light, but yields and reaction times may be dramatically improved by the use of pure, flowing oxygen and a 350-nm light source (Table 10).

In the solution phase, cation radical oxygenations are considerably enhanced by the presence of weak nucleophiles such as acetate155. The nucleophile is believed to function as shown in Scheme 61. Use of tetraethylammonium acetate in acetonitrile for photooxygenations considerably increases the yield of benzaldehydes and reduces the yield of minor products over a range of substituted stilbenes, as shown in Table 11.

1332

Daniel J. Berger and James M. Tanko

Ph

Ph

PIET O2

O O

O

Ph

Ph

Ph

Ph

O

O

Ph

Ph

H

H

Ph

ratio:

93

:

7

SCHEME 59

Ph2 C

CH2

no solvent

Ph2 C

O

98%

fluorescent light

2% w / w

air, agitation

on silica gel

48h, 23% conversion

no solvent

Ph2 C

O

98%

350 nm hν

O2 , agitaion

4h, 23% conversion

SCHEME 60

Recently, a general synthesis of ˛-formyloxycarbonyl compounds was reported. Yields ranging from 35 90% were achieved via electrochemical generation of enol carbonate cation radicals in DMF156. The cation radicals are trapped by the solvent, and the resulting formiminium ion is hydrolyzed during workup. The mechanism is shown in Scheme 62.

c. Nucleophilic addition to alkenes promoted by one-electron oxidation. In general, nucleophilic addition to alkenes only occurs when the alkene is activated by an electronwithdrawing substituent (e.g. a Michael addition). Oxidation of an alkene to its radical cation, however, provides a means decreasing -electron density, without having to introduce a substituent. Hole-catalyzed nucleophilic addition to electron-rich alkenes also yields the anti-Markovnikoff product. In hole-catalyzed nucleophilic addition to asymmetric stilbenes, addition of an amine nucleophile occurs at the carbon bearing the less electron-donating aryl group, probably because of greater stabilization of the resulting distonic radical cation (Scheme 63, An D p-CH3OC6H4)157.

22. Radical anions and cations derived from CDC, CDO or CDN groups 1333

TABLE 10. Yields of solvent-free alkene photooxygenation on silica or aluminaa

Compound Adsorbent, Time Conversion Yield (%)

gasb (h) (%)

	Ph2CDCH2	silica	48	23
		air
	Ph2CDCH2	alumina	48	75
		air
	Ph2CDCH2	silica	4	25
		O2
	Ph2CDCH2	alumina	4	60
		O2
	H3 C	silica
	CH2		4	3
		air
	Ph
	H3 C	alumina
	CH2		4	41
		air
	Ph
	An	silica
			4	23
		O2
	CH3
	Ph	silica	22	85
		O2
		silica	72	64
	Ph	air
	Ph	silica	72	98
		air
	Ph

OH

Ph2 C

O

Ph2 CCH3

98

OH

2

Ph2 C

O

Ph2

CCH3

Ph2 CHCHO

97

1

2

Ph2 C

O

Ph2 CHCHO

98

2

Ph2 C

O Ph2 CHCHO

96

1

H3 C

H3 C

O

O

Ph

Ph

98

2

H3 C

H3 C

O

OH

O

PhC(CH3 )2

Ph

Ph

71

O

6

23

AnCHO AnCH2

CCH3 An

CH3

52

3

O

45

O

Ph

(CH2 )4 CHO

Ph

(CH2 )4 CO2 H

37

46

PhCHO

Ph

O

8

92

PhCHO

Ph

O

53

42

a Reference 154.

b ‘Air’ includes irradiation under fluorescent light; ‘O2’ includes irradiation by a 350-nm source. Alumina is acidic.

Addition of nucleophiles to 1,1-diarylethylenes has also been reported to give the antiMarkovnikoff product158, interestingly, solvent polarity may have a strong effect on the stereochemistry of addition (Scheme 64), though no mechanism has been suggested which explains this result158b.

d. Oxidative C C bond-forming reactions. A variety of synthetically useful C C bondforming processes involving >CDC<žC intermediates have been reported, several of which are summarized herein. These oxidations may be carried out electrochemically, via PIET, or chemically. Ceric ammonium nitrate and copper(I,II) systems have also found a

use in oxidative cyclization reactions159, as well as electrochemically-generated halonium (XC ) ions160.

1334			Daniel J. Berger and James M. Tanko
					O
Ar				Ar	O					O O
			O2			− Nu
Nu		Ar ′							Ar		Ar ′
				Nu	Ar ′
		Nu: −
Ar					O O
	+		O2		+					aldehyde
		Ar ′		Ar	Ar ′

			O
			+
		Ar	Ar ′				epoxides
		SCHEME 61
TABLE 11. Results	of photooxygenation of		substituted	stilbenes		(PhCHDCHAr)		with 9-
								a
cyanoanthracene catalyst in the presence of tetraethylammonium acetate (yields given in percent)
Ar	Solvent	PhCHO	ArCHO	Epoxide			Otherb	Recovery
								(Z:E)
Ph	MeCN	79						20 (5:5)
Phc	MeCN	37		13		4		29 (4:6)
4-MeC6H4	MeCN	82	77					0
4-MeC7H4c	MeCN	28	24	24				7 (7:3)
4-MeOC6H4	MeCN	93	66					0
4-MeOC6H4c	MeCN	31	19	65				38 (4:6)
3,5-(MeO)2C6H4	MeCN	53	44					61 (7:3)
4-MeC6H4	CH2Cl2	32	23			44		72 (3:7)
4-MeOC6H4	CH2Cl2	46	34	20		10		5 (0:1)

a Reference 155.

b Benzil (ArDPh) or Ph(AcO)CDCHAr (solvent = CH2Cl2). c No acetate salt added.

Perhaps the most useful type of alkene substrates for these reactions are enol ethers, enol esters and vinyl sulfides. Silyl enol ethers have excellent electron-donor properties, with an ionization potential of about 8 eV and an oxidation potential in various solvents of approximately 1.0 1.5 V vs SCE161. These compounds are easily synthesized by reaction of an enolate with a chlorosilane. (A very recent report synthesized a variety of silyl enol ethers with extremely high stereochemical yield, using the electrogenerated amidate of 2- pyrolidinone as the base.)162 An interesting point is that the use of oxidative or reductive cyclization reactions allows carbonyl functionalities to be ambivalent, either oxidizable or reducible (Scheme 65)163.

22. Radical anions and cations derived from CDC, CDO or CDN groups 1335

OCO2 CH3

O

DMF/LiClO4

H2 O

OCHO

R

carbon anode

workup

R

H2 O

− e−

O

OCO2 CH3

O

CH3

O

O

+

H

N(CH3 )2

O

+

N(CH )

R

3

2

R

H

− H3 C

− CO2

O

+

O

N(CH3 )2

R

H

SCHEME 62

AnCH2

CHPh

sole product

NR2

+ e−

H + shift

H

H

Ph

H

Ph

H

Ph

An

+

− e−

HNR

R2 NH

+ 2

An

H

An

H

H

Ph

An

H

R NH

2

+

H + shift

+ e−

AnCHCH2 Ph

not observed

NR2

SCHEME 63

1336	Daniel J. Berger and James M. Tanko

CH3 CN

C6 H6

O

CO2 R

− H +

+ SiMe3 +

SiMe3

O

CO2 R

+ MeOH

Ph

hν / DCA

+

OMe

Ph

3.8:

1

:

SCHEME 64

O−

+ e−

CO2 R

SiMe3

+O

− e−

CO2 R

OMe

Ph

1 89%

3.291%

OH CH2

+ H +

CO2 R

+ H

OH CH3

CO2 R

CH2

− SiMe3 +

O

CO2 R

+ H

CH3

O

CO2 R

SCHEME 65

22. Radical anions and cations derived from CDC, CDO or CDN groups 1337

Anodic oxidation of cyclic enol esters with ˇ-hydrogens leads to allyl radicals, which then lose ‘acyl radical’ to form ˛, ˇ-unsaturated ketones. When the electrolysis is performed in an undivided cell, these are converted by the cathode into enolate anion radicals, which then couple to form ˇ-dimers (Scheme 66)164.

However, the greatest amount of work in the area of intramolecular cation-radical coupling reactions involves annulation of less ionizable alkenes (or alkynes) with enol ethers or vinyl sulfides. Typically, these reactions are used to form six-159,163 or fivemembered165 rings, usually stereospecifically (Schemes 67 and 68, respectively). As seen

R

OAc

R

OAc

R

OAc ‘A c •’ R

O

− e−

+

−H +

( )n

( )n

( )n

( )n

H

H

+ e−

graphite

undivided cell

glacial A cOH

anode

and cathode

R

R

•O

R R

O−

O

O

O−

R

+ e−

+ 2H

+

( )n

( )n

R

O

( )n

( )n

( )n

n = 2, 3

(

)n

R = Me, Et, i-Pr

SCHEME 66

SiR3

O

H

Cu(OTf)2 / Cu2 O

H

0 °C

87%

H

− e−

− e−

− H +

+ O

SiR3

O

H

− R3 Si

+

H

H

H

SCHEME 67

1338	Daniel J. Berger and James M. Tanko

in Scheme 68, intramolecular anodic coupling of enol ether cation radicals to allylsilanes in methanol leads to vinylcycloalkanes. This may be exploited as shown in Scheme 69166.

X		H	X
			OMe
R1	MeOH	•	+
	Pt anode		R1
	X =OMe, Ph, OSiR3		R2
2			OMe
R	R1, R2 =various
		MeOH
X +		X +
•		•
R1			R1
		•

R2	R2

SCHEME 68

X

H

OMe

•

R1

(R2 =CH2 SiR3 )

MeOH

X +

•

•SiMe3

R1

MeOH / A cOH

~100% overall

	OMe	OMe			OMe
R′	( )n
	R′	( )n	OMe R′	( )n	OMe
R′	MeOH		+
	SiMe3 Pt anode
			R′
	R′				SiMe3
	R
		R		R	OMe

SCHEME 69

Intramolecular anodic coupling of enol ethers to vinylsilanes generates carbon carbon bonds while breaking the vinyl silicon bond; this may be used either to form new rings or to place a vinyl group where it is needed (Scheme 70)167.

Alkyl enol ethers and vinyl sulfides may also be oxidatively annulated onto electron-rich aromatic rings (Scheme 71)168.

In a fine display of the versatility of the technique, the Moeller group has produced fused, biand tricyclic enones stereospecifically in good yield (Scheme 72)169.

3. Reactions involving >CDC<ž

Generally, carbon is not sufficiently electronegative such that alkene radical anions can be generated in solution without the presence of at least one activating substituent,

22. Radical anions and cations derived from CDC, CDO or CDN groups 1339

OMe OMe OMe

Me3 Si

+ OMe

MeO

+

MeO

MeOH

Pt anode

− e−

+ OMe

H

SiMe3

OMe

O

Si

− e−

Si

O

MeO

+

52%

+ MeOH

− H +

− Me3 Si

	H
SiMe3
	MeO
MeOH	MeO
Pt anode

+ 2MeOH

−e−

−2H+

+

MeO

OSiMe2

SCHEME 70

OSiMe2 OMe

72%

typically Ar, NO2, C N or CDO. Because of this requirement, and by virtue of the fact that both charge and spin are delocalized over the entire -framework in such systems, it becomes somewhat a matter of semantics as to whether such species are truly ‘alkene’ radical anions. The most numerous examples of such species, radical anions involving a CDO activating substituent generated from ˛, ˇ-unsaturated ketones, aldehydes and esters, have already been discussed separately in the context of reactions involving >CDOž . This section completes the presentation of the chemistry pertaining to >CDC<ž .

1340	Daniel J. Berger and James M. Tanko
MeO		MeO
			72%
		MeOH
		Pt anode
MeO		MeO
	SMe	MeO	SMe

1. MeOH

Y Pt anode Y 2. H+

X		MeO	X
Y =O, X =SMe		Y =O, X =SMe 54%
		X =OMe 17%
Y =O, X =OMe		Y =O, X =OMe 75%
Y =NR, X =SMe		Y =NR, X =SMe 66%
(R=pivaloyl)

SCHEME 71

a. Z ! E isomerization. One of the most studied reactions of alkene radical anions is Z ! E isomerization (equation 39)170. Addition of an electron to the Ł orbital of an alkene results in a reduced -bond order, and the barrier to rotation becomes significantly less than that of the neutral alkene. The kinetics of this process has been studied extensively, and this particular property of alkene radical anions has been used to ‘probe’ for single electron pathways in several reactions171.

R	R		R		H
	•			•
	−			−	(39)
H	H		H		R

b. Reduction/dimerization of alkenes. The electrochemical reduction of alkenes can lead to the formation of the corresponding alkanes or dihydro dimers172. Recently, an example of an electrocatalytic variant of this process, the reduction of fumaronitrile, was reported173. On the basis of results obtained from cyclic voltammetry, a mechanism for the process was suggested (Scheme 73, DMVC2 D 4, 40-dimethyl-1,10 -trimethylene-2,20- dipyridinium ion).

An investigation recently demonstrated that upon one-electron reduction vinylcyclopropanes undergo cyclopropane ring opening with retention of CDC (Scheme 74, DBBž D 4, 40-di-t-butylbiphenyl radical anion)174. Substrates without phenyl substitutents on the cyclopropane ring were found not to react under the reaction conditions, suggesting that the phenyl group, rather than the >CDC<, was the electrophore. Initial ring opening was suggested to proceed at the radical anion stage, in analogy to the cyclopropylcarbinyl ! homoallyl radical rearrangement.