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 1301

TABLE 5. Products arising from photoinduced electron transfer to ˛,ˇ-epoxyke- tone 18a

O		hν			O	O	O	OH
	Ph						+
Ph		Et3 N		Ph		Ph
							Ph	Ph
	O
(18)						(19)		(20)
Solvent		%19					%20
CH3CN		60					22
CH3OH		49					28
CH3CN/LiC		70					0

a Reference 60.

Ring openings of ˛,ˇ-epoxyketones can also be accomplished electrochemically, although most of the work in this area deals with the synthetic aspects of this reaction. Shapiro, Gentles, Kabasakalian and Magatti reported that electrochemical reduction of epoxyketone 26 yields ring-opened products 27 and 28 (equation 15)61. Although the overall yield for this reaction was quite low (35%), it was noted that chemical reducing agents were ineffective at promoting this transformation.

	O	O
	O
		OH
	e−	(15)
HO	HO
(26)		(27) trans: 29%
		(28) cis: 6%

Inokuchi, Kusumoto and Torii reported the electrochemical reduction of epoxyketone 29 at a carbon cathode (equation 16)62. In the absence of a proton source, two deoxygenated products (enone 30 and pinacol dimer 31) were produced in a combined yield of 37%. However, in the presence of a proton source (CH2(CO2Et)2), ring-opened product 32 was produced in 65% overall yield.

O			O		O
			HO		)2
	e	−	+		+
O	THF/H2 O					OH
	n-Bu4 NBF4
(29)			(30)	(31)	(32)	(16)

Sml2-promoted ring opening of ˛,ˇ-epoxyketones have also been reported. In 1986, Molander and Hahu reported that aliphatic epoxyketones produce ring-opened products

1302	Daniel J. Berger and James M. Tanko

upon treatment with Sml2 in the presence of methanol in high yield63. However, these authors suggest that ring opening occurs after protonation of the initially formed ketyl anion and a second electron transfer (Scheme 19). Analogous ring openings of ˛,ˇ- epoxyesters have also been reported, proceeding in yields of 30 70% (depending on reaction conditions and additives)64.

O

			Sml2				O
n-Bu
			THF			n-Bu			OH
		O
		Sm+2
		Sm+3
	O−						OH
n-Bu						n-Bu			O−
		O
		CH3 OH
		CH3 O −
	OH						OH
n-Bu		Sm+2		Sm+3			−
						n-Bu
		O
									O
			SCHEME 19

Finally, ring opening of ˛,ˇ-epoxyketones can be accomplished using n-Bu3SnH (equation 17)65. These reactions can be initiated either photochemically or via a thermal initiator such as AIBN. For the photochemical reaction, initiation occurs via excitation of the ketone to its triplet state, which abstracts hydrogen from n-Bu3SnH.

	O		O	OH
	C5H11	n-Bu3 SnH		(17)
		hν or ln2 /∆
	CH3
				C5H11

O

40−80%

(c) Aziridine ring openings. There have been very few reports regarding opening of aziridine rings via ketyl radical anions. In 1989, Stamm’s group reported the reductive ring opening of N-benzoylaziridine via reaction with dihydroanthracene and n-BuLi (equation 18)66. The key step of their proposed mechanism involves ring opening of an intermediate aziridine radical anion (equation 19).

	22. Radical anions and cations derived from CDC, CDO or CDN groups							1303
	O						R
		R		A H2	AH
						NHCOPh	NHCOPh
Ph	N			n-BuLi
					R	R
		R		THF			R
						0−25%	73−100%	(18)
		AH2		=
	O−					O−
		R				R		(19)
					Ph	N
Ph	N	R

R

Ring opening of 2-acylaziridines can be accomplished in high yield using Sml2 to give masked ˇ-aminoketones (e.g. equation 20)67. The details of the mechanism (i.e. whether ring opening occurs at the ketyl anion or ketyl radical stage, or after a second electron transfer, Scheme 20) are unclear at this time.

	O					O
		Sml2				95%	(20)
CH3		THF / MeOH			CH3
	NTs					NHTs
	O−					O
						−
	R	NTs			R
						NTs

	OH		OH
R	NTs	R	NTs

	OH			OH
R	−	NTs		−
			R	NTs

SCHEME 20

1304	Daniel J. Berger and James M. Tanko

(d) Fourand five-membered ring openings. In 1983, Liotta reported the use of dienone 33 as a probe for SET. The radical anion generated from 33 undergoes ring opening according to Scheme 2168. The generation of an aromatic ring provides the thermodynamic driving force for this ring opening. This system has been used to assess the importance of SET in reactions of ketones with (CH3)2CuLi, RMgX and RLi. Detection of alcohol 34 was cited as evidence for SET in several of these reactions.

	O	O−	O	OH
		e−
O	O	O	O	O
			O
			O−	OH
	(33)			(34)

SCHEME 21

There has been considerable interest in the mechanism of action of DNA photolyase enzymes, which repair pyrimidine dimers in damaged DNA via action of visible light. Several model reactions have given credence to a possible SET pathway. For example, Falvey and coworker reported that the photochemical reaction of dimer 35 with FADH2 results in a retro [2 C 2] cycloaddition according to Scheme 2269.

	O	O			O−	O
	HN		NH	FA DH2	HN		NH	+
				hν				/ FADH2
O	N	N	O	O	N	N		O
	(35)
			O−	O			O−
		HN		NH		HN		O
			N	+		O	N	/ FADH2 +
	O			N	O
								N
								O
	O
	HN
O	N

SCHEME 22

22. Radical anions and cations derived from CDC, CDO or CDN groups 1305

Similarly, electrochemical reduction of 36 results in a 65% yield of the retro [2 C 2] cycloadditon product (equation 21). The rate constant for the conversion 36ž ! 37 C 37ž was determined to be 3.0 s 1 by cyclic voltammetry70.

O	O		OH
		e−
		CH3 CN	(21)
		n-Bu4 NPF6
		Pt cathode	65%
O	O		OH
	(36)		(37)

Radical-stabilizing substituents on the cyclobutane ring appear necessary for this ring opening to occur. Yang and Begley found no evidence for ring opening of radical anion 38 (equation 22, generated via PIET using N,N-dimethylaniline)71. Neither ring-opened products nor isomerized starting material (resulting from a reversible ring opening) were detected.

	O−			O−
	H	H			H
		C5H11
	N		X	N	H
					(22)
O	N	D	O	N	C5H11
	H	H		H	D
				H
	(38)

e. Addition of >CDOž to -systems (ketone olefin coupling reactions). Generation of

>CDOž in the presence of an olefin (or other unsaturated functionality) may lead to an addition process as outlined in Scheme 23. Depending on the method of generation and the reaction conditions, the radical portion of the adduct may abstract a hydrogen atom from the solvent, or be further reduced to a dianion which can be trapped by electrophiles (usually, but not always, HC ). This methodology is particularly valuable when the addition reaction is intramolecular, and is an effective means for the synthesis of fiveand six-membered rings.

(i) Intermolecular additions. In 1989, Shono’s group reported that aliphatic ketones reduced (electrochemically) in the presence of an olefin yield the ketone/olefin adduct in reasonable yield (e.g. equation 23)72 presumably via a mechanism analogous to that outlined in Scheme 23. The selection of the cathode material was critical to the success of this reaction; carbon fiber was found to give the highest yield of coupling product. The addition step was sensitive to steric effects, with addition to less substituted double bonds favored. This technology was applied to the one-step synthesis of bisabolol (39) in 80% yield (equation 24).

1306

Daniel J. Berger and James M. Tanko

O

OH

e

−

CH3 CCH2 CH3 + CH2

CH(CH2 )5CH3

CH3

C(CH2 )7CH3

(23)

DMF

n-Bu4 NBF4

CH2 CH3

77%

O

HO

+

(39) (24)

	O				O−				R1		R3
	C	e	−					R3	C
R1					C				R2
			1			2
	R2				•				O_
				R		R
									SH
								S			e−
									R1		R3
						H	+		C		−
									R2
									O_
					R1	C		R3	E +, H+
					R2
						OH
									R1		R3
									C
									R2
									OH		E

SCHEME 23

In an interesting extension of this methodology, Shono demonstrated that this reaction was especially effective when an allylic alcohol was utilized instead of a simple alkene. For example, reduction of acetone in the presence of 40 yields adduct 41 in 71% yield and greater than 85% diastereomeric excess73. The high diasteroselectivity observed for this process is rationalized to arise from hydrogen bonding interactions between the oxygen of >CDOž and hydroxyl group of the allylic alcohol which direct the addition to the si face of the double bond (Scheme 24).

An intriguing variant of this coupling process was reported in 1995. Treatment of acetone with Sml2 in the presence of 42 resulted in the formation of allene 43 in 81% yield and a 5.7:1 diastereomeric ratio (equation 25)74. Although no mechanism was suggested, it is likely that the reaction involves addition of (CH3)2CDOž to the terminal alkyne,

22. Radical anions and cations derived from CDC, CDO or CDN groups 1307

CH3

n-Bu

CH3

n-Bu

O−

O

e

−

(40) OH

O

CH3 CCH3

CH3 CCH3

CH3

H

C

O−

CH3

CH3

CH3

CH3

n-Bu

CH3

n-Bu

C

2H +

e −

C

HO

−O

CH3

OH

CH3

OH

(41)

SCHEME 24

followed by subsequent ring opening of the oxiranyl radical (Scheme 25)75.

			HO
O	+ CH3 COCH3	Sml2	•
			H (25)
			OH
(42)			(43)
O−			O−
CH3 CCH3 +	O		H
			O

HO

•

H

O•

SCHEME 25

(ii) Intramolecular additions. (a) Intramolecular additions to remote alkene or allene functionalities. When a radical center is created in a molecule possessing a remote CDC or other unsaturated functionality, intramolecular addition may occur resulting in the formation of a cyclic compound. (This reaction is formally the reverse reaction of ˇ- cleavage.) The 5-hexenyl neutral free radical rearrangement (equation 26) is a classic example of such a process. In addition to providing an important mechanistic tool both

1308	Daniel J. Berger and James M. Tanko

for detecting alkyl radical intermediates in a variety of chemical processes and for measuring the rates of competing bimolecular reactions (i.e. a free radical ‘clock’)76, this rearrangement has emerged as an important synthetic method for the synthesis of fivemembered rings77. Over the past decade, numerous examples have been reported of the radical anion equivalent of this reaction, involving intramolecular additions of >CDOž to remote unsaturated functionalities.

(26)

In 1986, Belotti, Pete and Portella reported that intramolecular ketone/olefin coupling could be achieved via photoinduced electron transfer (irradiation of an aliphatic ketone in HMPA)78. Several examples of this chemistry are highlighted below (Scheme 26). Intramolecular additions to C C and allenes were also reported with yields in the range 70 80%; however, additions to C N were unsuccessful.

				OH	CH3
	O		hν		81% (n = 1)
( )n			Et3 N	( ) n	76% (n = 2)
			HMPA
				H
O			hν	OH	OH
					CH3 +		CH3
			Et3 N
			HMPA
				45%	30%
		O		OH

hν

67%

Et3 N

HMPA

H

SCHEME 26

The centerpiece of this chemistry involves cyclization of a ketyl anion (produced by PIET: >CDO C R3N : C h ! >CDOž C R3NžC ) as outlined in equation 27.

O−	O−
	(27)
C	R
R

Analogous cyclizations can also be accomplished electrochemically79. In 1988, KarivMiller’s group reported that cyclization of enone 44 could be achieved at a mercury electrode in the presence of dimethylpyrrolidinium ion (DMPC )80. DMPC was a critical component for the success of this reaction, as direct reduction in the absence of DMPC

22. Radical anions and cations derived from CDC, CDO or CDN groups 1309

produced only reduced product 45 (Scheme 27). DMPC was found to serve as a mediator (catalyst) for electron transfer to the carbonyl. Reduction of DMPC at Hg yields a species of composition (DMP)Hg5, which has been independently prepared. (DMP)Hg5 subsequently reduces the carbonyl compound DMP Hg5 C >CDO ! DMPC C 5Hg° C >CDOž 81.

Cyclizations involving esters were reported by Shono and workers in 1992 utilizing a Mg electrode82. Different products arose when the reduction was conducted in the presence of t-BuOH vs (CH3)3SiCl (Scheme 28).

O

(44)

e−

DMF

Hg cathode n-Bu4 NBF4

OH

(45)

SCHEME 27

e −

Mg cathode LiClO4 , THF

CO2 Me

e− t-BuOH

_O OCH3

DMP+ e− DMF

Hg cathode n-Bu4 NBF4

CH3

OH

CH3

(46)

OCH3

O_

60%

HO

(CH3 )3 SiCl e−

67%

TMSO

SCHEME 28

1310	Daniel J. Berger and James M. Tanko

A tandem cyclization was accomplished electrochemically in 1989 (Scheme 29). A 50% yield was reported, depending on conditions83.

A number of intramolecular ketyl anion/olefin coupling reactions promoted by Sml2 have been reported since 1985. In general, Sml2 reactions give extremely high yields and exhibit high diasteroselectivity.

Several examples of intramolecular ketyl anion/unactivated olefin coupling reactions were reported by the Molander group, one of which is illustrated in equation 2884. An interesting facet of this reaction is that it is possible to further react the cyclized samarium(III) intermediate (47) with a variety of electrophiles, thereby enhancing the

O

e−

DMF

n-Bu4 NBF4 Hg cathode

O−

−O

CH2

H

SCHEME 29

O

Sm+2 Sm+3

	Sm(III)
−O	Sm+2

HO

H

−O

CH2

H

O−

O−

(47)	E
E +	HO

SCHEME 30