SPOTLIGHT2880

SYNLETT

Spotlight 294This feature focuses on a re-agent chosen by a postgradu-ate, highlighting the uses andpreparation of the reagent incurrent research

Bestmann–Ohira Reagent: A Versatile Reagent in Organic SynthesisCompiled by Umesh Daga Patil

Umesh D. Patil was born in Pimpri (Mondhale), Jalgaon, India, in1984. He pursued his B.Sc. in chemistry (2005) from Kisan Ma-havidyalaya Parola, affiliated to North Maharashtra University(NMU), Jalgaon, India, and his M.Sc. in Organic Chemistry (2007)at the Department of Organic Chemistry, NMU. At present he isworking towards his Ph.D. at the same department under the guid-ance of Dr. Sidhanath V. Bhosale. His research interests include thesynthesis of biologically active heterocyclic compounds using ringtransformations.

Department of Organic Chemistry, North Maharashtra University, Umavinagar, Jalgaon 425001, IndiaE-mail: umesh123patil@gmail.comDedicated to Professor S. L. Patil

SYNLETT 2009, No. 17, pp 2880–2881xx.xx.2009Advanced online publication: 02.10.2009DOI: 10.1055/s-0029-1218101; Art ID: V29809ST© Georg Thieme Verlag Stuttgart · New York

Introduction

Bestmann–Ohira reagent [(1-diazo-2-oxopropyl)phos-phonate] can be prepared by the reaction of dimethyl-2-oxopropylphosphonate, TosN3

1a or p-acetamidobenzene-sulfonyl azide,1b NaH, t-BuOK or Et3N in benzene andTHF. An alternative is the preparation using polymer-sup-ported sulfonyl azide and t-BuOK in methylenchloride.1c

The Bestmann–Ohiro reagent is widely used in the con-

version of primary alcohols, aldehydes, ketones, andamides into alkynes. Recently, it was employed in thesynthesis of pyrazoles as well as 1,3-oxazoles.

Scheme 1

Abstracts

O

P

O

OMeOMe

N2

Bestmann–Ohirareagent

O

P

O

OMeOMe

TosN3, NaH or Et3N

C6H6, THF

1. NaH, PhMe

2. p-acetamido- benzenesulfonyl azide in THF

O

P

O

OMeOMe

(A) The use of the Bestmann–Ohira reagent is an alternative to theFritsch–Buttenberg–Wiechell-type rearrangement and the Corey–Fuchs procedure that allows the addition of the reagent to an alde-hyde under mild reaction conditions, thus avoiding the use of astrong base under low-temperature conditions. The reaction workswith alkyl and aryl as well as hindered aldehydes. In case of a,b-unsaturated aldehydes the main products were isolated as homopro-pargylic methyl ethers. The reaction can be easily performed underone-pot conditions.2

(B) Hamilton D. Dickson and co-workers reported that esters andamides undergo reduction to the corresponding aldehydes usingDIBAL-H followed by in situ conversion into terminal alkynes uti-lizing the Bestmann–Ohira reagent in good to excellent yields.3 Ad-ditionally, chiral nonracemic substrates undergo this transformationwith complete preservation of stereochemical integrity.3

(C) E. Quesada et al. described the direct conversion of activated pri-mary alcohols into terminal alkynes through a sequential one-pot,two-step process involving oxidation with manganese dioxide andthen treatment with the Bestmann–Ohira reagent. This transforma-tion proceeds efficiently (59–99% yield) under mild reaction condi-tions with a range of benzylic, heterocyclic, and propargylicalcohols.4

RCHOK2CO3, MeOH

r.t., 4–18 hR HBestmann–Ohira

reagent

RCHO K2CO3, MeOH

r.t.

R

OMe

R

Bestmann–Ohirareagent

R1 HBestmann–Ohira

reagentR1

O

OR4

1. DIBAL-H, CH2Cl2, –78 °C

2.orR1

O

NR3

R2

Bestmann–Ohirareagent

2.

OHX X

X = NO2 X = CO2Me

1. MnO2

SPOTLIGHT 2881

Synlett 2009, No. 17, 2880–2881 © Thieme Stuttgart · New York

References

(1) (a) Callant, P.; D’haenens, L.; Vandewalle, M. Synth. Commun. 1984, 14, 155. (b) Pietruszka, J.; Witt, A. Synthesis 2006, 4266. (c) Harned, A. M.; Sherrill, W. M.; Flynn, D. L.; Hanson, P. R. Tetrahedron 2005, 61, 12093.

(2) Müller, S.; Liepold, B.; Bestmann, H. J. Synlett 1996, 521.(3) Dickson, H. D.; Smith, S. C.; Hinkle, K. W. Tetrahedron

Lett. 2004, 45, 5597.(4) Quesada, E.; Taylor, R. J. K. Tetrahedron Lett. 2005, 46,

6473.(5) Muruganantham, R.; Mobin, S. M.; Namboothiri, I. N. N.

Org. Lett. 2007, 9, 1125.

(6) Gong, D.; Zhang, L.; Yuan, C. Synth. Commun. 2004, 34, 3259.

(7) Clay, M. D.; Fallis, A. G. Angew. Chem. Int. Ed. 2005, 44, 4039.

(8) Barrett, A. G. M.; Hopkins, B. T.; Love, A. C.; Tedeschi, L. Org. Lett. 2004, 6, 835.

(9) Bartnik, R.; Lesniak, S.; Wasiak, P. Tetrahedron Lett. 2004, 45, 7301.

(10) Gilbert, J. C.; Weerasooriya, U. J. Org. Chem. 1982, 47, 1837.

(11) Ohira, S. Synth. Commun. 1989, 19, 561.

(D) 1,3-Dipolar cycloaddition of the anion of diethyl 1-diazometh-ylphosphonate, generated in situ from Bestmann-Ohira reagent, withconjugated nitroalkenes provided regioisomerically pure phospho-nylpyrazoles in moderate to good yield. These pyrazoles are formedin one pot via spontaneous elimination of the nitro group.5

(E) D. Gong et. al. prepared a series of 4-phosphoryl-substituted 1,3-oxazoles conveniently by reaction of Bestmann–Ohira reagent andaromatic nitriles in the presence of a catalytic amount of rhodium(II)acetate.6

(F) Oxidation of epoxy alcohol by Dess– Martin periodinane gave analdehyde which was subsequently treated with the Ohiro reagent togive an epoxy alkyne in 93% yield.7

(G) Barrett and co-workers prepared ROMPgel-supported ethyl 1-diazo-2-oxopropylphosphonate and employed this reagent in theconversion of a variety of aldehydes into terminal alkynes.8 The useof polymer-supported Ohiro reagent led to high product yield.

(H) The cycloaddition of diethyl 1-diazomethylphosphonate withbenzylidine alkylamines afford (1-alkyl-5-phenyl-4,5-dihydro-1H-[1,2,3]triazol-4-yl)-phosphonic acid diethyl ester.9

(I) Gilbert et al. described the base-promoted reaction of dimethyl(diazomethyl)phosphonate with aldehydes and aryl ketones at lowtemperature. The alkynes are obtained in modest to excellentyields.10

(J) The Bestmann–Ohira reagent itself was used for the preparationof enol ethers or alkynes from carbonyl compounds in the presenceof excess potassium carbonate and methanol.11

O

POEt

N2

Bestmann–Ohirareagent

X

NO2

R

NaOEt, EtOH0.5–24 h, r.t. X

NHN

R

P

EtO

O

OEt

OOEt

R = Ar, Hetar or HX = O, CH

NO2

X

NaOEt, EtOH5–10 min, r.t.

NH

N

PR

X

O OEt

OEt

R = Ar, Hetar, NMe2X = H, Br, NO2

R1

O

POEt

N2

Bestmann–Ohirareagent

OOEt Rh2(OAc)4 (1 mol%)

85 °C O N

R2

R1 P

O

OEt

OEt

+ R2CN

TIPS

OHO

1. Dess–Martin periodinane

2. Ohira reagent

TIPS

O

R H

O

R = Alk, Ar

ROMP O P

O

EtON2

O

polar ROMPgel swells in MeOH

K2CO3, MeOHR

H

63–91% yield

N2CHPO(OEt)2N

Ph H

R

MeOH

r.t., 3 d NN

NR

Ph POEt

OEt

O

+

N2CHPO(OEt)2 ArCORn-BuLi or t-BuOK

ArC CR+

O

R1

R2

R3

Bestmann–Ohirareagent

R1

R2

R3

OMe

K2CO3, MeOH