HYPOPHOSPHOROUS ACID

1

Hypophosphorous Acid

1

H

3

PO

2

[6303-21-5]

H

3

O

2

P

(MW 66.00)

InChI = 1/H3O2P/c1-3-2/h3H2,(H,1,2)/f/h1H
InChIKey = ACVYVLVWPXVTIT-OKIMJQNECY
(tautomer)
[14332-09-3]
InChI = 1/H3O2P/c1-3-2/h1-3H
InChIKey = XRBCRPZXSCBRTK-UHFFFAOYAT

(reduction of aromatic diazonium salts,

1,2

nitro compounds,

3

and

pyrrole derivatives;

4

synthesis of organic derivatives of hypophos-

phorous acid;

1,5,6

generation of selenols

7

)

Alternate Name:

HPA.

Physical Data:

mp 26.5

◦

C; decomposes at 140

◦

C; d 1.493

g cm

−3

(19

◦

C); pK

a

1.1.

Solubility:

soluble in water, alcohol, ether, dioxane.

Form Supplied in:

widely available as 50% aqueous solutions

(d 1.274 g mL

−1

).

Preparative Methods:

the anhydrous acid is prepared from the

commercial solution or from inorganic salts.

1,8

Handling, Storage, and Precaution:

decomposes upon heating

above 140

◦

C into H

3

PO

4

and poisonous, spontaneously flamm-

able PH

3

. Slowly decomposes at rt. Air sensitive. Use in a fume

hood.

Original Commentary

Vladimir V. Popik
St. Petersburg State University, St. Petersburg, Russia

Reduction of Arenediazonium Compounds. Hypophospho-

rous acid is widely accepted as the preferred reagent for the reduc-
tion of diazonium salts.

1,2,9

Copper(I) Oxide is a very effective

catalyst of this reaction

9

(eq 1). Dediazonation with HPA can also

be used in Pschorr-type cyclizations.

10

Cl

Cl

N N

+

Cl

Cl

H

3

PO

2

, Cu

2

O, CHCl

3

BF

4

–

(1)

97%

Alkylphosphinic Acids. Radical addition of HPA or its alkali

salt to alkenes is initiated by organic peroxides and gives phos-
phinic acid derivatives in good yields (eq 2).

1,6,11,12

The alkene

to HPA ratio controls the formation of alkyl- or dialkylphosphinic
acid.

1,11

Alkyl phosphinates also add to alkenes in the presence

of peroxides.

1

Alkylphosphinic acids can be prepared from HPA

and alcohols,

13

and alkenylphosphinic acids have been obtained

from enol esters.

14

P

O

OH

+

H

3

PO

2

dioxane, (t-BuO)

2

H

(2)

70%

Hydroxyalkylphosphinic Acids. HPA reacts with aldehydes,

ketones, and 1,2-ketones to provide 1-hydroxyalkylphosphinic
acids (eq 3).

1

When carbonyl compounds are used in excess, bis(1-

hydroxyalkyl)phosphinic acids are formed.

Cl

3

C

O

H

Cl

3

C

OH

P

O

OH

+

H

3

PO

2

65%

H

(3)

1,2-Alkadienylphosphinic Acids. Reactions of HPA with

alkynic alcohols are accompanied by alkyne–allene rearrange-
ment and lead to 1,2-alkadienylphosphinic acids (eq 4).

15

HO

R

1

R

2

R

3

P

R

3

O

OH

•

R

2

R

1

+

H

3

PO

2

benzene, reflux

(4)

H

R

1

= R

2

= H; R

3

= CH

2

OH

96%

Aminoalkylphosphinic Acids. HPA reacts with azomethines

under mild conditions, providing good yields of 1-(alkylamino)
alkylphosphinic acids.

1

Synthetic possibilities of this reaction

have been extended by replacing the azomethines with a mix-
ture of aldehyde or ketone and amine or hydrazine.

6,16

Thus re-

action of HPA with equimolar amounts of formaldehyde and sec-
ondary amines at rt in aqueous solution gives the corresponding
dialkylaminophosphinic acids (eq 5). With an excess of amine
and formaldehyde, bis(dialkylaminoalkyl)phosphinic acids are
formed.

1,16

P

O

OH

N

NH

Me

Me

O

H

H

Me

Me

+

H

3

PO

2

+

20 °C

H

(5)

81%

Alkyl Hypophosphites. A particularly easy preparation of

alkyl hypophosphites involves the reaction of crystalline HPA
with orthocarbonyl compounds (eq 6).

5

Treatment of HPA with

diazoalkanes also gives good yields of the desired esters.

17

Reac-

tion of HPA with orthoformates in the presence of p-Toluenesul-
fonic Acid leads to the formation of alkyl dialkoxymethylphos-
phinates.

18

H

P

O

OR

OR

RO

OR

(6)

H

H

P

O

OH

+

1–30 min

H

R = Et

–ROH, –HCO

2

R

57%

Reduction with Hypophosphorous Acid. Palladium on Car-

bon catalyzed reduction with HPA converts the nitro group of
arenes into an amino group,

3

and quinones into hydroquinones.

19

HPA in combination with Hydrogen Iodide is used for reduction
and reductive alkylation of pyrrole derivatives.

4

Avoid Skin Contact with All Reagents

2

HYPOPHOSPHOROUS ACID

Selenols. A commercial 50% solution of HPA is a convenient

reagent for generation of selenols from diselenides or selenic
acids.

7

First Update

Andrew G. Wright, Tanweer A. Khan & John A. Murphy
University of Strathclyde, Glasgow, UK

Non-radical Uses of Hypophosphorous Acid (HPA).

Addition of HPA to α

α

α

,β

β

β

-Unsaturated Amides. Cates and Li

20

reported the first synthesis of a phosphinic acid containing an
amido group (1), using HPA in the addition to acrylamide (2)
(eq 7). Reaction between HPA and methacrylamide with ethanol as
solvent gave only methacrylamide polymer as the product. Com-
pound 1 is the sole example of a phosphinic acid possessing an
amido side-chain.

H

3

PO

2

NH

2

O

NH

2

O

H

2

O

2

P

2

1, 73%

(7)

+

Reaction of HPA Salts with Alkyl Halides.

Devedjiev et

al.

21

reported that alkali metal salts of HPA react with alkyl

halides through a variant of the Michaelis–Bekker reaction. When
potassium hypophosphite was reacted with excess 3-chloro-1,2-
propanediol (3), 2,3-dihydroxypropylphosphinic acid (4) was
formed (eq 8).

P OK

HO

H

Cl

OH

OH

P

OH

OH

HO

H

O

4

(8)

3

+

This has also been applied

22

to the reaction with appropriate

halogenated polymers, e.g., PVC and polychloroprene rubber.

Direct Amidoalkylation of HPA. The synthesis of aminoben-

zylphosphinic acids by the amidoalkylation of HPA using N,N

′

-

arylidene bisamides has been reported by Tyka and Hägele.

23

The

reaction of bisamides (5) with HPA and acetic acid gave interme-
diate 6 which, upon treatment with hydrochloric acid and propy-
lene oxide, gave product 7(eq 9). Only bisamides prepared from
aromatic aldehydes undergo these reactions.

Synthesis of α

α

α

-Aminophosphonic Acids Using HPA. Hamil-

ton and co-workers

24

developed a convenient route to opti-

cally pure α-aminophosphonic acids by reacting the HPA salts
of R-(+) or S-(−) N-α-methylbenzylamine (8) with a vari-
ety of aldehydes in refluxing ethanol to form intermediate
α

-aminophosphinic acids followed by simultaneous deprotection

and oxidation to give pure α-aminophosphonic acids (9) in high
optical purity (eq 10).

1. Hydrochloric acid

2. Propylene
oxide

R C

H

NH

2

PO

2

H

2

7

R C

H

NHCOMe

NHCOMe

H

3

PO

2

R C

H

NHCOMe

PO

2

H

2

CH

3

CO

2

H

5

6

(9)

R = X-C

6

H

4

(X = H, Cl, Me, OMe, NO

2

, Br)

31–72%

NH

3

H

2

PO

2

Ph

+

–

RCHO

EtOH

NH

Ph

R

P

OH

H

NH

2

R

P

O

(OH)

2

O

Br

2

/H

2

O

8

9

(10)

Synthesis of Oxazaphosphinanes.

Cristau et al.

25

reacted

HPA with imine 10 to give phosphinic acid 11 which undergoes
intramolecular esterification to give oxazaphosphinane 12 in 55%
yield (eq 11).

H

3

PO

2

N
H

P

OH

H

OH O

OH

N

O

N
H

P H

O

10

MeOH

reflux

69%

+

11

12

55%

DCC/DMAP

(11)

A list of General Abbreviations appears on the front Endpapers

HYPOPHOSPHOROUS ACID

3

Preparation

of

Hypophosphite

Esters.

Deprèle

and

Montchamp

26

have synthesized hypophosphite esters using

alkoxysilanes. They found that anilinium hypophosphite (AHP,
13) reacted with orthosilicates in a wide range of solvents (e.g.,
benzene, cyclohexane, toluene, THF, dioxane, acetonitrile, DMF)
to give the corresponding hypophosphite esters (14) in excellent
yields (eq 12).

P

MO

H

H

O

O

P

RO

H

H

13, M = PhNH

3

Si(OR)

4

solvent

heat

85–100%

14

(12)

HPA-iodine as a Novel Reducing System. Fry and co-workers

developed a novel reducing system using HPA and a catalytic
amount of iodine in refluxing acetic acid.

27

The reduction of diaryl

ketones (15) to diaryl methylene derivatives (16) has been reported
in an excellent yield, and it was found that diaryl ketones reduce
much more readily than aryl-alkyl ketones which, in turn, are
reduced more rapidly than dialkyl ketones (eq 13).

O

H

3

PO

2

, I

2

CH

3

COOH

reflux

98%

(13)

15

16

Subsequently, Fry applied this reducing system to the reduction

of benzhydrols

28

and of diarylethenes

29

to diarylethane deriva-

tives. Acetic acid has proven to be the solvent of choice for this
system. Reduction of benzhydrols was slow or negligible in chlo-
roform or benzene and conversion to the methyl ether was ob-
served using methanol. The issue of selective reduction has also
been addressed and it was found that when an equimolar mixture
of benzophenone and 3,4-dimethylbenzhydrol was reacted under
the standard reducing conditions, the alcohol was converted com-
pletely to 3,4-dimethyldiphenylmethane without any detectable
reduction of benzophenone to diphenylmethane.

28

Radical Uses of HPA.

Radical Deoxygenation and Dehalogenation Using HPA.

Barton et al.

30

reported that HPA can be used for the defunc-

tionalization of several functional groups. Radical chain deoxy-
genations can be carried out using phosphorus-centered radicals
generated from hypophosphorous acid or its salts with initia-
tion by 2,2

′

-azobis(2-methylpropionitrile) (AIBN). When treated

with HPA and a tertiary nitrogen base (e.g., triethylamine or
N

-ethylpiperidine) in boiling dioxane, alcohol thiocarbonyl

derivatives (17) were deoxygenated to give 18 in excellent yield.
The tertiary nitrogen base protects the thiocarbonate moiety as
well as any acid labile protecting groups from acidic hydrolysis
during the reaction (eq 14). This method is applicable to thio-
carbonyl derivatives of primary, secondary, and tertiary alcohols.
Radical dehalogenation reactions have also been achieved using
this method with iodide 19 and bromide 20 similarly giving hydro-
carbon 18 in excellent yields (eq 14). Further radical deoxygena-

tions and dehalogenations with HPA have been reported by Barton
et al.

31

X

H

H

3

PO

2

AIBN

base

Dioxane

reflux

17, X = O-C=S(SMe)
19, X = I
20, X = Br

18, X= H, 100%
18, X = H, 100%
18, X = H, 95%

(14)

Jang

32

subsequently reported that radical dehalogenation can

also be achieved in water, as opposed to toxic organic solvents.
The synthesis of enantiopure (R)-malates from (R,R)-tartrates via
cyclic thionocarbonates using a HPA/Et

3

N/AIBN system in diox-

ane at 80

◦

C has been reported by Jang and Song.

33

Synthesis of Monosubstituted Phosphinic Acids. Deprèle and

Montchamp

34

reported that phosphorus-centered radicals, gener-

ated by initiation with triethylborane and oxygen, can react with a
wide variety of alkenes to give monosubstituted phosphinic acids
(21) in good to excellent yields (eq 15). When the reaction was
attempted with electron-deficient alkenes, the yields were greatly
reduced. These radical reactions are conducted at room temper-
ature in an open flask without the use of potentially explosive
peroxide initiators.

P

MO

H

H

O

R

O

P

MO

H

R

Et

3

B/O

2

MeOH

(15)

21

70–98%

M = Na, PhNH

3

Intramolecular

Carbon–Carbon

Bond

Formation.

Hypophosphite-mediated carbon-carbon bond formation was
developed in the 1990’s to avoid the problems associated with tri-
butyltin hydride.

35−40

The reaction by-products are water-soluble

and easily separated, and HPA is considerably more econom-
ical than either tributyltin hydride or tris(trimethylsilyl)silane
(TTMSS).

Radical Addition to Alkynes. The first published example of

carbon-carbon bond formation using HPA and its salts was car-
ried out

35

by Calderon and co-workers. Stoodley and co-workers

36

followed this with the construction of near-stereopure quaternary
carbon stereogenic centers in molecules such as 22 starting from
alkyl bromides such as 23. These cyclizations, which were me-
diated by N-ethylpiperidine hypophosphite (EPHP) and initiated
by AIBN in refluxing toluene, gave the cyclized product in high
yield (eq 16).

O

OR

Me

O

Me

22

O

O

Me

Br

OR

H

Me

EPHP
AIBN

Toluene

reflux

79%

23

(16)

Avoid Skin Contact with All Reagents

4

HYPOPHOSPHOROUS ACID

Radical Addition to Alkenes. Carbon-carbon bond formation

has also been accomplished using HPA and its salts via addition
of carbon radicals to alkenes in a 5-exo-trig cyclization. The first
example of this sort of carbon-carbon bond formation was reported
by Murphy and co-workers

37

when they reacted aryl iodides (24)

with EPHP and AIBN in refluxing toluene to give the 5-exo-trig
cyclized products (25) in moderate yields. Alkyl bromides (26)
gave the cyclized products (27) in good to excellent yields (eq 17).

O

O

Br

R

′

R

R

′′

H
Me
Me
H

O

I

R

′

R

R

′′

H
Me
Me
H

O

R

′′

R

R

′

O

O

R

′′

R

R

′

H

H

H
H
Me

H
H
H

24

25

64
63
66
64

Cyclohexyl

R

R

H
H
Me

H
H
H

EPHP (10 equiv)

AIBN (0.4 equiv)

5-exo-trig

EPHP (10 equiv)

AIBN (0.4 equiv)

5-exo-trig

26

27

85
94
81
76

Cyclohexyl

(17)

R

′

R

′′

Yield (%)

R

′

R

′′

Yield (%)

Murphy and co-workers

38

have since applied this methodology

to the total synthesis of the phytotoxic metabolites epialboatrin
(28) and alboatrin (29), which were synthesized via 5-exo-trig
cyclization of bromochroman (30) to give 28 and 29, in a 6.7:1
ratio and a yield of 77% (eq 18).

O

TBSO

Br

O

O

O

HO

H

O

O

HO

H

EPHP
AIBN

Benzene

30

77%

28

29

(18)

Oshima

39,40

has also shown that salts of HPA can be used to

mediate radical cyclizations onto alkenes in aqueous ethanol using
triethylborane and oxygen as initiator.

Synthesis of Indoles Using HPA Fukuyama and co-workers

41

have used the HPA/AIBN/Et

3

N system to synthesize a variety

of 2,3-disubstituted indoles. Cyclization of o-alkenylthioanilide
precursor 31 proceeds smoothly to furnish the corresponding 2,3-
disubstituted indole 32 in a good yield (eq 19).

OH

NH

S

71%

N
H

OH

31

32

(19)

H

3

PO

2

AIBN

Et

3

N

n

-PrOH,

∆

Fukuyama

42

has applied this methodology in the total synthe-

sis of the Iboga alkaloid (±)-catharanthine (33). Cyclization of
the thioanilide precursor 34 gives indole 35 in 40–50% yield, a
considerable improvement in the yield obtained (12–22%) for the
same reaction using tributyltin hydride (eq 20). These conditions
are particularly effective for the construction of indoles bearing
sterically demanding substituents in the 2-position.

N
H

N

CO

2

Me

AcO

Z

N
H

S

N

CO

2

Me

AcO

Z

AIBN

H

3

PO

2

NEt

3

1-Propanol

34

35

N
H

N

CO

2

Me

33

(20)

Radical Cyclization of Hydrophobic Substrates in Water.

Kita et al.

43

reported that a combination of water-soluble radi-

cal initiator 2,2

′

-azobis[2-(2-imidazolin-2-yl)propane] (VA-061),

water-soluble chain carrier EPHP, and surfactant cetyltrimethyl-
ammonium bromide (CTAB) gave the optimum conditions for
carrying out radical cyclizations of hydrophobic substrates in
water in an excellent yield (eq 21).

A list of General Abbreviations appears on the front Endpapers

HYPOPHOSPHOROUS ACID

5

MeO

I

N

Ms

CTAB

H

2

O, 80

°C

98%

VA-061

EPHP

MeO

N

Ms

(21)

Intermolecular Carbon–Carbon Bond Formation. Jang and

co-workers

44

have reported the first intermolecular radical carbon-

carbon bond formation by HPA or its salts. They studied the radical
addition of alkyl halides (36) to electron-poor alkenes (37) with
triethylborane/oxygen as initiator and dioxane as solvent to give
addition product 38 in high yields (eq 22).

R X

Y

R

Y

SO

2

Ph

SO

2

Ph

P(O)(OEt)

2

R

Y

EPHP, Et

3

B

Dioxane, O

2

, rt

adamantyl

adamantyl

36

37

38

(22)

Yield (%)

98

94

97

C

6

H

11

Jang and Cho

45

have subsequently applied this methodology

to the formation of intermolecular carbon-carbon bonds in water.
They have found that this reaction requires the addition of indium
metal in order for addition to the alkene to take place. They have
also found that under aqueous conditions addition of cyclohexyl
radicals, generated from cyclohexyl iodide (39), to an α,β-enone
40 produces the 1,4-addition product 41 regioselectively, whereas
allylindium reagents generate the 1,2- or 1,4-addition product,
depending on the substrate, under ionic conditions (eq 23).

In, EPHP

CTAB, ABCVA

H

2

O, 80

°C

I

O

O

39

40

41

89%

(23)

1.

Yudelevich, V. I.; Sokolov, L. B.; Ionin, B. I., Russ. Chem. Rev. (Engl.
Transl.) 1980

, 49, 46.

2.

(a) Wulfman, D. S., In The Chemistry of Diazonium and Diazo Groups;
Patai, S., Ed.; Wiley: New York, 1978; Part 1, p 286. (b) Fieser, M.;
Fieser, L. F., Fieser & Fieser 1967, 1, 489.

3.

(a) Nasielski, J.; Moucheron, C.; Nasielski-Hinkens, R., Bull. Soc. Chim.
Belg. 1992

, 101, 491. (b) Nasielski-Hinkens, R.; Leveque, P.; Castelet,

D.; Nasielski, J., Heterocycles 1987, 26, 2433.

4.

(a) Gregorovich, B. V.; Liang, K. S. Y.; Glugston, D. M.; MacDonald, S.
F., Can. J. Chem. 1968, 46, 3291. (b) Khan, S. A.; Plieninger, H., Chem.
Ber. 1975

, 108, 2475. (c) Corbella, A.; Gariboldi, P.; Jommi, G.; Mauri,

F., Chem. Ind. (London) 1969, 583.

5.

(a) Baudler, M., In Organic Phosphorus Compounds; Kosolapoff,
G. M.; Maier, L., Eds.; Wiley: New York, 1973, p 1. (b) Livantsov,
M. V.; Prishchenko, A. A.; Lutsenko, I. F., J. Gen. Chem. USSR (Engl.
Transl.) 1985

, 55, 2226.

6.

Kleiner, H.-J., Methoden Org. Chem. (Houben-Weyl) 1982, E1, 271.

7.

(a) Labar, D.; Krief, A.; Hevesi, L., Tetrahedron Lett. 1978, 41, 3967.
(b) Synthetic Methods of Organic Chemistry; Theiheimer, W., Ed.;
Karger: Basel, 1968; Vol. 22, p 19.

8.

Handbook of Preparative Inorganic Chemistry

; Brauer, G., Ed.;

Academic: New York, 1963, p 555.

9.

Korzeniowski, S. H.; Blum, L.; Gokel, G. W., J. Org. Chem. 1977, 42,
1469.

10.

Dattolo, G.; Cirrincione, G.; Almerico, A. M.; Aiello, E.; D’Asdia, I., J.
Heterocycl. Chem. 1986

, 23, 1371.

11.

Nifant’ev, E. E.; Magdeeva, R. K.; Dolidze, A. V.; Ingorokva, X. X.;
Samkharadze, L. O.; Vasyanina, L. K.; Bekker, A. R., J. Gen. Chem.
USSR (Engl. Transl.) 1991

, 83.

12.

Broan, C. J.; Cole, E.; Jankowski, K. J.; Parker, D.; Pulukkody, K.; Boyce,
B. A.; Beeley, N. R. A.; Millar, K.; Millican, A. T., Synthesis 1992, 63.

13.

Devedjiev, I.; Ganev, V.; Stefanova, R.; Borisov, G., Phosphorus Sulfur
Silicon 1987

, 31, 7.

14.

Holt, D. A.; Erb, J. M., Tetrahedron Lett. 1989, 30, 5393.

15.

(a) Belakhov, V. V.; Yudelevich, V. I.; Komarov, E. V.; Ionin,
B. I.; Petrov, A. A., J. Gen. Chem. USSR (Engl. Transl.) 1984, 920.
(b) Devedjiev, I.; Ganev, V.; Borisov, G.; Zabski, L.; Jedlinski, Z.,
Phosphorus Sulfur Silicon 1989

, 42, 167.

16.

(a) Dhawan, B.; Redmore, D., J. Chem. Res. (S) 1988, 34. (b) Synthetic
Methods of Organic Chemistry

; Theiheimer, W., Ed.; Karger: Basel,

1971; Vol. 25, p 357. (c) Kapura, A. A.; Shermergon, I. M., J. Gen.
Chem. USSR (Engl. Transl.) 1989

, 1137.

17.

Kabachnik, M. J.; Shipov, A. E.; Mastrjukova, T. A., Izv. Akad. Nauk
SSSR, Ser. Khim. 1960

, 146.

18.

(a) Gallagher, M. J.; Honegger, H., Aust. J. Chem. 1980, 33, 287.
(b) Bailie, A. C.; Cornell, C. L.; Wright, B. J.; Wright, K., Tetrahedron
Lett. 1992

, 33, 5133.

19.

Entwistle, I. D.; Johnstone, R. A. W.; Telford, R. P., J. Chem. Res. (S)
1977, 117.

20.

Cates, L. A.; Li, V. S., Phosphorus Sulfur 1984, 21, 187.

21.

Devedjiev, I.; Ganev, V.; Stefanova, R.; Borissov, G., Phosphorus Sulfur
1988, 35, 261.

22.

Devedjiev, I.; Ganev, V.; Borissov, G., Eur. Polym. J. 1988, 24, 475.

23.

Tyka, R.; Hägele, G., Phosphorus Sulfur Silicon 1989, 44, 103.

24.

Hamilton, R.; Walker, B.; Walker, B. J., Tetrahedron Lett. 1995, 36,
4451.

25.

Cristau, H. J.; Monbrun, J.; Tillard, M.; Pirat, J. L., Tetrahedron Lett.
2003, 44, 3183.

26.

Deprèle, S.; Montchamp, J. L., J. Organomet. Chem. 2002, 643, 154.

27.

Hicks, L. D.; Han, J. K.; Fry, A. J., Tetrahedron Lett. 2000, 41, 7817.

28.

Gordon, P. E.; Fry, A. J., Tetrahedron Lett. 2001, 42, 831.

29.

Fry, A. J.; Allukian, M.; Williams, A. D., Tetrahedron 2002, 58,
4411.

30.

Barton, D. H. R.; Jang, D. O.; Jaszberenyi, J. C., Tetrahedron Lett. 1992,
33

, 5709.

31.

Barton, D. H. R.; Jang, D. O.; Jaszberenyi, J. C., J. Org. Chem. 1993,
58

, 6838.

32.

Jang, D. O., Tetrahedron Lett. 1996, 37, 5367.

33.

Jang, D. O.; Song, S. H., Tetrahedron Lett. 2000, 41, 247.

34.

Deprèle, S.; Montchamp, J.-L., J. Org. Chem. 2001, 66, 6745.

Avoid Skin Contact with All Reagents

6

HYPOPHOSPHOROUS ACID

35.

Pat. 97-EP2284 970506 (to Calderon, J. M. B.; Chicharro, G. J.;
Fiandorn, R. J.; Huss, S.; Ward, R. A.).

36.

McCague, R.; Pritchard, R. G.; Stoodley, R. J.; Williamson, D. S., Chem.
Commun. 1998

, 2691.

37.

Graham, S. R.; Murphy, J. A.; Coates, D., Tetrahedron Lett. 1999, 40,
2415.

38.

Graham, S. R.; Murphy, J. A.; Kennedy, A. R., J. Chem. Soc., Perkin
Trans. 1 1999

, 3071.

39.

Yorimitsu, H.; Shinokubo, H.; Oshima, K., Chem. Lett. 2000, 104.

40.

Yorimitsu, H.; Shinokubo, H.; Oshima, K., Bull. Chem. Soc. Jpn. 2001,
74

, 225.

41.

Reding, M. T.; Kaburagi, Y.; Tokuyama, H.; Fukuyama, T., Heterocycles
2002, 56, 313.

42.

Reding, M. T.; Fukuyama, T., Org. Lett. 1999, 1, 973.

43.

Kita, Y.; Nambu, H.; Ramesh, N. G.; Anilkumar, G.; Matsugi, M., Org.
Lett. 2001

, 3, 1157.

44.

Jang, D. O.; Cho, D. H.; Chung, C. M., Synlett 2001, 1923.

45.

Jang, D. O.; Cho, D. H., Synlett 2002, 631.

A list of General Abbreviations appears on the front Endpapers