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 1321

+

An

(excess)

direct hν Pyrex

no solvent

H3 C CH3

HH

An

PIET 92 min

CH3

CH3

An

CH3

+

A r3 N +

−30 ° C

A r3 N +

55 sec

0 ° C, 10 min

(or PIET)

H

CH3

H

CH3

H3 C

CH3

H

H +

H

H

H

CH3

An

H

CH3

An

An

(64)

(64)

sole product

A r3 N +

or PIET

CH3

CH3

CH3

CH3

+

An

An

CH3

CH3

SCHEME 41

	CH3
CH3
Electrochemically-	PIET-
induced	induced

Yield:	22%	28%
endo/exo:	9:1	4:1

SCHEME 42

endo-selectivity. Nevertheless, selectivity may be altered somewhat by varying reagent or electrolyte concentrations, by using different PIET acceptors or by selective quenching123.

Important general aspects of the cation-radical ‘Diels Alder’ reaction and other cationradical sigmatropic reactions are summarized below:

ž There is a wide range of possible catalysts available for initiating the reaction. In addition to organic salts, oxidants such as hydrated or anhydrous FeCl106a3 and ceric

ammonium nitrate106a,124 have proven effective.

ž Electrochemical methods should be avoided because their chief electrooxidative reaction involving olefins is polymerization.

1322	Daniel J. Berger and James M. Tanko
	A	+	Z		A	+	Z
				fast
			Z		E
		+		×		+
	E		Z		E		Z
	E	+ S			ES
	ES	+	Z		ES	+	Z
	A = acceptor, S= substrate,
	Z = (Z)-stilbene, E = (E)-stilbene

SCHEME 43

ž Cation radicals of (Z)-alkenes isomerize to the more stable (E)-isomer before adding to a substrate (Scheme 43). Despite this, in the case of stilbene, it is often found that none of the (E)-isomer is recovered from the reaction mixture. This is due to the fact that electron transfer from (Z)-stilbene to (E)-stilbenežC is highly endothermic111,125.

Indoles, which are especially electron-rich and thus unsuitable for ordinary Diels Alder reactions, have performed successfully in the cation-radical reaction as dienophiles (Scheme 44)107 and as dienes (Scheme 45)126. Interestingly, the site of annulation (across the C C or the C N bond) in vinylindole cation radicals (functioning as dienes for eneamine dienophiles) may be manipulated by varying the substituent on the enamine and thereby altering its push pull nature (Scheme 45).

			O				TPP (5 mol%)
	+				+		hν / CH2 Cl2
N	CH3 CCl						NaHCO3	, 6 h		N
H							15 °C
				Ph					O	CH3
TPP =						−
						BF4
	Ph			O		Ph
		+

SCHEME 44

For the indole, methyl sustitution at the 2-position (i.e. 71) appears to sterically block C C annulation vs C N annulation (Scheme 46)126a. Note also that electrochemical methods are only useful for the substituted vinylindoles, as unsubstituted indoles passivate the working electrode. The results of cycloadditions of substituted enamines 66 and 69 to vinylindoles 65 and 71 are summarized in Tables 7 and 8.

Another interesting variation on hole-catalyzed Diels Alder chemistry involves the use of electrochemically-oxidized phenols as dienes. A set of cycloaddition reactions leading to bicyclic products was reported in 1991, beginning from polysubstituted phenols127. This work strongly implicated cation 74 by showing that the same products were obtained when 74 was generated independently via Brønsted acid/base reactions (Scheme 47).

Similarly, phenoxonium ion 75 was believed to be a key intermediate in the intramolecular process (Scheme 48)128.

22. Radical anions and cations derived from CDC, CDO or CDN groups 1323

			+ Me2 N		CO2 Me
		N
			CH3
		H
		CN
	(65)				(66)
			CH2 Cl2 , A r, 15 °C			TPP (5 mol%), hν
			−HNMe2 , −2H+, −2e−
			CO2 Me
						N		CN
								+
			N		CH3			CH3
			H
			CN			CO2 Me
			(68)			(67)
						CN
		CH3	TPP (5 mol%), hν					CH3
65 +
		CN	CH2 Cl2 , A r, 15 °C			N
	Me2 N		−HNMe2 , −2H+, −2e−					CH3
						H
						CN
	(69)					(70)
			SCHEME 45
		TABLE 7. Results of PIET-induced cycloaddition of indole diene
		65 with dienophile 66a
		[66] (mmol L 1)	mol% of TPPb		67:68	Yield (%)
						(67 C 68)
	7.7		8		3.5:1	85
	5.9		6.9		2.6:1	80
	2.7		6.1		1.5:1	75

a Reference 107.

b TPP D 2,4,6-triphenylpyrilium tetrafluoroborate.

A later study of the intermolecular addition suggested that electron transfer between the phenoxonium ion and alkene is an important pathway to products (Scheme 49)129.

(ii) Vinylcyclopropane rearrangements. The vinylcyclopropane ! cyclopentene rearrangement (equation 37) has emerged as an important method for the preparation of functionalized cyclopentenes130. Formally, the thermal process is symmetry-forbidden,

and exhibits an activation energy of 50 kcal mol 1131 . This reaction can also be induced

1324	Daniel J. Berger and James M. Tanko

photochemically, or via the use of appropriate Lewis acids.

(37)

			R			R
		R			R
		CH3
		+			CO2 Me
	N			Me2 N
			CH3
	H	CN
	(71)			(66)
		Carbon anode, 15 °C		CH2 Cl2 / CH3 CN 1:1
		−HNMe2 , −2H+, −2e−		0.1 M LiClO4 , A r
				CH3
				CN
				N
				CH3
				CO2 Me
				(72)
	CH3		CH2 Cl2 / CH3 CN 1:1			CH3
	71 + Me2 N	CN	0.1 M LiClO4 , A r
			Carbon anode, 15 °C			NMe2
			−HCN, −2H+, −2e−			N
	(69)

CH3

CO2 Me

(73)

SCHEME 46

TABLE 8. Results of PIETor electrochemically-induced cycloaddition of indole dienes with dienophilesa

Diene	Dienophile	Initiationb	Time (h)	Product
				(yield %)
65	66	PIET	5.5	67 (74), 68 (22)
71	66	e-chem	2	72 (32)
65	69	PIET	6	70 (13)
71	69	e-chem	2	73 (29)
a Reference 126.				e-chem D carbon anode,
b PIET	D 5 mol% 2,4,6-triphenylpyrilium tetrafluoroborate, h ;

0.1 M LiClO4.

22. Radical anions and cations derived from CDC, CDO or CDN groups 1325

Y

X

OH

MeO Y

X

O

HO

O

			Y		R
Z				Z
	− 2e−		+		R′
	−H +				(Z = OMe)
		X
			O
			(74)
	+H +			+ MeOH
	− MeOH			− H+
Z			Y
				Z	R
		MeO			R ′
		X
			O

SCHEME 47

R

CH3 CN/CH3 OH 4 :1 30 equiv. A cOH

Pt Anode, 97%

O

X

R

Y

O

R′

R′ R

Z O

X

Y

OMe

R

OMe

O

−2e− −H +		+ MeOH
		− H +
R
		R
+	O	+

(75)

SCHEME 48

In 1988, Dinnocenzo and Conlon reported a radical cation variant of this reaction

(Scheme 50)132. Most of the relevant material pertaining to this reaction has been recently reviewed112.

Some question, however, exists as to the extent of ring-opening which exists in cyclopropyl and vinylcyclopropyl cation radicals133. Addressing this point, an elegant 1994 study found that (1R,5R)-(C)-subinenežC (76, which cannot rearrange to a cyclopentene

1326	Daniel J. Berger and James M. Tanko

OMe

Ar

+

HO

−2e− −H +

OMe

+ Ar

+

O

+

An

+

An

+

An

		Pt anode	R
		LiClO4	OMe
		CH3 CN	Ar
	R	A cOH
		up to 80%	O

OMe

		Ar
		+	+
	R		R
			•O
	SCHEME 49
	An +	H

+ e− An H X

not stabilized

An +

+ e− An

H

stabilized

An +

+ e− An

H

stabilized

An = p-CH3 OC6 H4

Conditions: 10 mol% Ar3 NSbCl6

CH3 CN, 22 °C, 5 min

SCHEME 50

because such a rearrangement would lead to a bridgehead double bond, equation 38) behaves as a stereorigid vinylcyclopropane radical cation (Scheme 51)134. Four possible spinand charge-delocalization patterns are possible in this vinylcylopropane cation radical, 77 ! 80. Ring-opened radical cation 80 would be expected to lead to a racemic mixture of products. However, this was not found and the product showed optical activity. Further elucidation of the products, formed by trapping of the cation radical with methanol and DCB anion radical, showed that the spin and charge distribution in sabinenežC was

22. Radical anions and cations derived from CDC, CDO or CDN groups 1327

as shown in 77.

(76)

(38)

		−e−
?	?	?	?
+	+	+	+
(77)	(78)	(79)	(80)
			MeOH
		OMe	NC	CN
			racemic products
	OMe		(not observed)
		(not trapped)
NC	CN
	trapping products

SCHEME 51

(iii) Epoxidations of alkenes. Hole catalysis has been proposed as a mechanism for epoxidations in the presence of TIET acceptors. In epoxidations using SeO2 or benzeneseleninic anhydride (BSA) in the presence of aminium cation radicals, Bauld and Mirafzal reported 60 90% yields, with complete regiospecificity, over a wide range of dienes and trienes. Their results are compared to the results of epoxidations using meta-chloroperbenzoic acid (MCPBA) in Scheme 52 and Table 9135.

However, most of the debate in this area has been over the mechanism of epoxidation by cytochrome P450 (c-P450) and its analogs. c-P450 is a monooxygenase whose active center is an iron(III) porphyrin136; its catalytic cycle is shown in Scheme 53137.

The two basic mechanistic possibilities for c-P450 epoxidations are summarized in Scheme 54. Path a represents an entirely covalent pathway involving oxidative addition

1328	Daniel J. Berger and James M. Tanko

a or b

a or b

a or b

O

(a)100

(b)45

O

(a)100

(b)55

O

+ O	O a =BSA, Ar3 N+
	b =MCPBA

(a)0

(b)55

O O

O

++

	(a) 0	(a) 0
	(b) 21	(b) 24
	O
+	+	+ diepoxides
		O

(a) 100

(a) 0

(a) 0

(a) 0

(b) 36

(b) 10

(b) 29

(b) 25

SCHEME 52

TABLE 9. Results of hole-catalyzed epoxidationa

Substrate

Oxidant

% Yield, GC (isolated)b

E-stilbene

SeO2c

80

(60)

Z-stilbene

SeO2

80

(58), epoxide of E

1,1-diphenylethylene

SeO2

70

(42)

ˇ-methylstyrene

SeO2

60

(35)

˛-methylstyrene

SeO2

65

(38)

Z-stilbene

BSAd

85

(65), epoxide of Z

BSA

83

(63)

BSA

76

(61)

BSA

72

(56)

a Reference 135.

b Column chromatography on silica gel.

c SeO

, 500 mol%, Ar

3

NSbCl , 20 mol%; CH Cl , 0 °C to RT, 1 h. Quench with K

2

CO

3

/CH

3

OH

2

6

2

2

d BSA 100 mol%; Ar3NSbCl6, 20 mol%; CH2Cl2, 0 °C. 10 min. Quench with K2CO3/CH3OH.

22. Radical anions and cations derived from CDC, CDO or CDN groups 1329

SO e−

Fe III

S

peroxide

shunt

XO

O

V

Fe

X

H2 O

O2 2 −

III

2H+

Fe

SCHEME 53

O

C

FeV

+ C C

path a

O C

FeV

Cl

Cl

Fe II

e−, O2

		III			O
Fe
		+			C C
Cl

path b

O−					C
			+		O C
FeIV		+
			C C		Fe IV
Cl					Cl
			SCHEME 54

and reductive elimination. Path b supposes the intermediacy of either caged or solventseparated radical ions (path b).

Initially, the products of these reactions suggested radical ions were involved138. In particular, when hexamethyl Dewar-benzene was epoxidized with MCPBA, the nature of the products depended on whether or not the iron(III) porphyrin hemin was added to the reaction mixture138b. Furthermore, when Z-stilbene was epoxidized with dioxygen, catalyzed by (tetraphenylporphorinato)iron(III) chloride, E-stilbene appeared in the reaction mixture139.

However, there has never been general agreement that alkene cation radicals were involved140. It was pointed out that choice of a c-P450 model will strongly influence the results: When manganese porphyrins were used, retention of alkene configuration

1330	Daniel J. Berger and James M. Tanko

depended on the oxidation state of the metal141. A 1989 paper by Garrison, Ostovic and Bruice142 concluded that the rate-determining step in metal-porphyrin-catalyzed epoxidations was formation of a CT complex between the metal and the alkene, and that whether an alkene cation radical is involved is sensitively dependent on the details of that complex.

Independent rate studies by Bruice and Castellino143 and by the Bauld group144 concluded that any alkene radical cation must have a lifetime less than about 10 12 s, ruling out any meaningful role in the reaction for the free species. More recent work has generally concluded that no alkene cation radical is involved in epoxidations catalyzed by iron(III)

Ph

Ph

+ Ar3 N+

+

+

Ar3 N :

Ph

Ph

Ph

N2

H

+

EtO2 C H

+

EtO2 C

N

+

+

2

N2

+

EtO2 CCH

Ph

Ph

Ph

Ph

Ph

EtO2 C H

+

EtO2 C

H

+ Ar3 N :

+ Ar3 N+

Ph

Ph

Ph

Ph

SCHEME 55

Ph C

CH

+

Ar3 N

+

Ar N:

Ph2 C

CH2

2

2

3

+

/+

+

Bu3 SnH+/

Ph2 C

CH2

Bu3 SnH

Ph2 C

CH3

H

/+

+

+

Bu3 Sn /+

Ph2 C

CH3

Bu3 SnH

Ph2 C

CH3

Bu3 Sn

+

Ar3 N

Bu3 Sn+

+ Ar3 N:

SCHEME 56

A r3 N +

An2 C

R3 SnH

HAn2 C

R = n-Bu, Ph

A r = p-BrC6

H4

95%

− e−

+ R3 SnH

− R3 Sn

+ R3 SnH

An2 C

An2 C

− R3 Sn +

+

H

An = p-CH3 OC6 H4

SCHEME 57