Ylides and Related Compounds

BY B. J. WALKER

1 Introduction Corey has recently updated the area of his computer-assisted synthesis program dealing with olefins, and the new material includes many examples of phosphorus- based olefin synthesis. Perhaps it augers well for a new Reporter for this Chapter that even sulphur ylides have found it necessary to adopt the behaviour normally associated with phosphonium ylides !

2 Methylenephosphoranes Preparation and Structure.-A variety of approaches to the synthesis of substi- tuted cyclopentadienyl ylides have been reported. Cyano-derivatives (2) and (4) can be prepared through copper(1)-catalysed reactions of the bromo-ylide (1)' and the substitution of the iodonium salt (3) at high temperat~re,~ respectively.

hPh, I

h h , I

C0,E t C\O,Et

. I

NC CN

Both phosphonium and sulphonium substituents can be introduced by electro- philic substitution; for example, Scheme 1 .

1 E. J. Corey and A. K. Long, J. Org. Chem., 1978,43, 2208. E. M. Burgess and M. C. Pulcrano, J. Am. Chem. SOC., 1978,100,6538. S . Yoneda, M. Watanabe, and Z. Yoshida, Bull. Chem. SOC. Jpn., 1978, 51, 2605.

K. H. Schlingensief and K. Hartke, Justus Liebigs Ann. Chem., 1978, 1754. 4 K. Friedrich, W. Aman, and H. Fritz, Chem. Ber., 1979, 112, 1267.

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Ylides and Related Compounds *

193

Scheme 1

Bridgehead phosphonium ylides and phosphine oxide anions based on the homocubane ring system have been synthesized.6 In the case of the phosphonium salt (S) , the corresponding ylide appears to be unstable with respect to the re- arranged product (6). However, the corresponding phosphine oxide anion (7) is more stable, and undergoes reaction with a variety of electrophiles XY to give the expected products. Cyclic ylides, for example (8), are the products of reactions of phospholes with dimethyl acetylenedicarboxylate (DMAD).‘

The di-ylide (10) and the mono-ylide (1 1) are among the products of the reaction of the copper-phosphine tetramer (9) with DMAD.* A variety of ylide complexes, e.g. (12),9 and the stable half-ylide (13) lo have been obtained from the reaction of carbyne-chromium complexes with trimethylphosphine.

6 J. P. Albarella and T. J. Katz, J. Org. Chem., 1978, 43, 4338. 7 D. G. Holah, A. N. Hughes, and D. Kleemola, J. Heterocycl. Chem., 1978, 15, 1319.

R. Ketari and A. Foucaud, Tetrahedron Lett., 1978, 2563. 9 F. R. Kreissl, W. Uedelhoven, and G. Kreis, Chem. Ber., 1978, 111, 3283. 10 F. R. Kreissl, K. Eberl, and W. Kleine, Chem. Ber., 1978, 111, 2451.

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194 Organophosphorus Chemistry

[ Ph,YCuCII, + 2MeO,CC=CCO,Me

(9 )

-+ Ph3P=C,

0 (1 1)

(10)

A variety of boron-containing phosphonium ylides have been prepared through lithiation of bis(trimethy1phosphine)boronium bromide (Scheme 2) and dimethyl- (methylene) [(trimethylphosphoranylidene)amino]phosphorane (Scheme 3). l1 The same group of workers have reported that treatment of dilithiated methylene- trimethylphosphorane with the disilylchloride (14) gives a mixture of exocyclic (15) and endocyclic (16) ylides.12 The novel bicyclic ylide (17) is obtained from a

Reagents: i, 2BuLi; ii, MeeBBr Scheme 2

Reagents: i, MeLi; ii, BHzCl, Et3N Scheme 3

11 H. Schmidbaur, H.-J. Fuller, G. Muller, and A. Frank, Chem. Ber., 1979, 112, 1448 18 H. Schmidbaur and M. Heimann, Chern. Ber., 1978,111,2696.

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Ylides and Related Compounds 195

+ 2MeP(CH2),Li, 4MeLi 2 M e,P=C H

1 2CH,[SiMe2C1], f

+

,SiMe,

SiMe, Me,P=C\

similar reaction of bis(trimethylsilyl)methylenetrimethylphosphorane. Appel has synthesized the carbodiphosphorane (19) from the silyldiphosphine (1 8) and carbon tetrach10ride.l~

SiMe, c1 c1

Ph,P=C=PPh, Ph,PCHPPh, 2cc14 + I

(18) (19)

Dimethylsilylenephosphorane (20) seems a likely intermediate in the reaction of hexamethylsiliran and tertiary phosphines with ketones to give (21).14 Novel phosphoranes containing a P-P bond have been prepared by P-phosphinylation of the biphosphine anion (22).16

0 Me,Si' 'CR1R2

1 / 2 1 I - V

1s R. Appel and K. Waid, Angew. Chem., Znt. Ed. Engl., 1979, 18, 169. 14 D. Seyferth and T. F. 0. Lim, J. Am. Chem. SOC., 1978, 100, 7074. '5 R. Appel, M. Wander, and F. Knoll, Chem. Ber., 1979, 112, 1093.

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196 Organophosphorus Chemistry

Attempts to prepare ylides of 1,3-diphosphonium salts lead to a number of novel rearrangements.l6 Examples are given in Scheme 4.

dre Me 21'

Me +A,+ Ph,P H PPh, -& I I Me Me

2 I-

Me CHMe,

Me

Ph,PHc\PPh I I

PhCH, Me

Reagents: i, 2 MesP=CHa, Et2O

Scheme 4

The phosphonium ylide (23) appears to be implicated in the addition of tri- phenylphosphine to trityl cation. l7 Arylazomethylenephosphoranes (24) have been prepared from hydrazonyl chlorides.

A large number of acylmethylenephosphoranes, many of them new compounds, have been prepared in connection with slP n.m.r. studies.ls An X-ray crystal structure of the carbodiphosphorane (25) has been carried out.20

16 H. Schmidaur and A. Wohlleben-Hammer, Chem. Ber., 1979,112, 510. 17 G. Bidan and M. Genies, Tetrahedron Lett., 1978, 2499. 18 P. Dalla Croce, P. Del Buttero, E. Licandro, and S. Maiorana, Synthesis, 1979, 299. 1 9 J. M. Brittain and R. A. Jones, Tetrahedron, 1979, 35, 1139. 20 H. Schmidbaur, G . Hasslberger, U. Deschler, U. Schubert, C. Kappenstein, and A. Frank,

Anpew. Chem.. Int. Ed. End.. 1979, 18, 408.

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Ylides and Related Compounds 197

Reactions.-AZdehydes. Displacement or transfer of an acetate group is known to occur in parallel with Wittig reactions; however, these are not observed during the synthesis of laurencin derivatives (26)21 or of the diene (27) en route to the plant pigment lachananthocarbone (Scheme 5). 23

OAc

C + Ph,P=CHC=CSiMe, Rx., I H' 'CH,CHO

6t

Reagents: i, KzC03, HzO; ii, PhCH=CHCHO

Scheme 5

For obvious reasons, Wittig reactions of terephthalaldehyde and isophthalalde- hyde with polymer-supported ylides lead to mono-olefination in 1 : 1 reactions." In 'conventional' reactions, the extent of mono- and di-olefination depends on the nature of the ylide, the halide counter-ion, and the reaction conditions. The use of ethylene oxide as a base 24 is especially effective in the generation of polymer- supported ylides, although formation of monoethylene acetal can become an important ~ide-reaction.~~ The Wittig reaction has also been used to modify polymeric reagents (Scheme 6)26 and to synthesize vinyltetrathiafulvalene (28) for polymerization studies.

Scheme 6

z1 T. Masamune, H. Murase, and A. Murai, Bull. Chem. SOC. Jpn., 1979,52, 135; ibid., p. 127. 23 A. C. Bazan, J. M. Edwards, and U. Weiss, Tetrahedron, 1978, 34, 3005. 33 J. Castells, J. Font, and A. Virgili, J. Chem. SOC., Perkin Trans. 1 , 1979, 1. 24 J. Buddrus and W. Kimpenhaus, Chem. Ber., 1974, 107, 2062. 25 J. A. Moore and J. J. Kennedy, J. Chem. SOC., Chem. Commun., 1978, 1079. 26 D. C. Green and R. W. Allen, J. Chem. Soc., Chem. Commun., 1978, 832.

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198 Organophosphorus Chemistry

(28)

Chloromethylenetriphenylphosphorane has been used to prepare vinyl chlorides (predominantly and as a source of the acetylenic group in a synthesis of brustulosin (Scheme 7).28 A Wittig reaction of the aldehyde-equili- brated hydroxy-lactones (29) has been used to synthesize cyclobutane analogues of chrysanthemic acids. 29

OR CH,OSiBu'Me, OH CHO Several steps

OR OH

Reagents: i, P h a P S H C l ; ii, ButMezSiCl; iii, NaNHz, NH3

Scheme 7

The Wittig reaction has been used in a standard way in the synthesis of diene~,~O e.g. (30),31 and t r i e n e ~ . ~ ~ The (12,3E)-(32; R= piperidinyl) and (12,32)-(33; R = piperidinyl) isomers of wisanine (32; R = piperidinyl) have been synthesized by Wittig reactions of (31) with maleinaldehyde in the absence and presence of lithium iodide respectively (Scheme 8). 33 The complementary approach of preserving the stereochemistry of the starting aldehyde has been used to synthesize hydroxy-dienes (Scheme 9). s4

H:7J R' R2

Ph,P=CMe, %:" R' R2

w S. Miyano, Y. Izumi, K. Fujii, Y. Ohno, and H. Hashimoto, Bull. Chem. SOC. Jpn., 1979,

18 A. F. Orr, J. Chem. Soc., Chem. Commun., 1979,40. ** H. D. Scharf, J. Janus, and E. Muller, Tetrahedron, 1979, 35, 25. 80 J. Font and P. March, Tetrahedron Lett., 1978, 3601, 81 M. E. Jung and B. Gaede, Tetrahedron, 1979, 35, 621. 3% C. W. Spangler, B. Keys, and D. C. Bookbinder, J . Chem. SOC., Perkin Trans. 2, 1979, 810. 31 H. D. Scharf and J. Janus, Tetrahedron, 1979, 35, 385. 34 K. Tatsuta, T. Yamauchi, and M. Kinoshita, BUN. Chem. SOC. Jpn., 1978, 51, 3035.

52,1197.

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Ylides and Related Compounds 199

Reagents: i, BuLi, THF; ii, H

H ; iii, H ~ ~ ~ 0 2 E , L i l OHCxCO&t OHC

Scheme 8

Me

CHO

P h F C H C 0 , R ~

Me < kO,R

Me M e

oi4 Ph,P=CHCO,R

Scheme 9

Examples of enaminophosphonium salts that undergo Wittig reactions include (34) and (35).58

(34) (35)

35 M. A. Calcagno and E. E. Schweizer, J . Org. Chem., 1978,43, 4207.

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200 Organophosphorus Chemistry

2-(1,3-Dioxan-2-yl)-ethylidenetriphenylphosphorane (36) has been used as a three-carbon homologating agent to give ./I- and &-unsaturated aldehydes (Scheme 10). 36 Perhaps surprisingly, the Corey-Schlosser approach3’ gives stereospecific formation of the (2)-allylic alcohol (Scheme 1 l).38

yR /“-7,HO

+ RCHO - R-17)

CIfO R-

(36) 40--70%

Reagents: i, HaO+; ii, HCI, CrC13, HaO.

Scheme 10

n . ... n HO

35 -45%

Reagents: i, PhsP=CHMe; ii, BunLi; iii, HCHO.

Scheme 11

The diastereomeric alkenes (37) have been prepared by a combination of phosphonate and Wittig olefination, for use in stereochemical investigations of cyclization to the steroid nucleus (Scheme 12).3D

The 7-oxo-l-azabicyclo [3.2.0]hept-2-ene ring system has been synthesized by an intramolecular Wittig reaction of (38).40

CIIO I -

n

Go ,CHR2

--CH R’

(37)

Scheme 12 36 J. C. Stowell and D. R. Keith, Synthesis, 1979, 132. 37 S. Trippett, in ‘Organophosphorus Chemistry’, ed. S. Trippett (Specialist Periodical Reports),

The Chemical Society, London, 1974, Vol. 5, p. 177. 38 W. G. Taylor, J. Org. Chem., 1979, 44, 1020. 39 A. A. Macco, J. M. G. Driessen-Engles, M. L. M. Pennings, J. W. De Haan, and H. M.

40 A. J. G. Baxter, K. H. Dickinson, P. M. Roberts, T. C. Smale, and R. Southgate, J. Chem. Buck, J. Chem. SOC., Chem. Commun., 1978, 1103.

SOC., Chem. Commun., 1979,236.

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YIides and Related Cornpounda 201

(38) A variety of meso-vinyl-porphyrins have been prepared from meso-formyl-

porphyrins (39) and phosphonium ylides. 41 Attempts to prepare a bis-porphyrin through a Wittig reaction with the bisphosphonium salt (41) and butyl-lithium gave only the meso-heptenyl derivative (a), through displacement of phosphine by butyl-lit hium.

(39) R' = CHO (40) R' = CH=CH(CII,).,Me

The mechanism of the reaction of two equivalents of phosphonium ylide (42) with methyl 4-oxobutenoate to give chrysanthemic esters (45) has been investi- gated.4s The diene (46) does not undergo cyclopropanation when treated with the ylide (42), and the authors provide good evidence that the pathway followed involves reaction of the betaine (43) with a second molecule of phosphonium

R' R2C -CH-CH=CHCO,Me

. (43) Ph,P=CR'R2LiX + OHCCH=CHCO,Me - I I

Ph,Pt 0' (42) b 2 )

Ph,P' I 0' 1 . R R C ' , I , , Ph,P 13

R'RZC--CW--HC-~HCO,M~

(45) (44) 41 D. P. Arnold, R. Gacte-Holmes, A. W. Johnson, A. R. P. Smith, and G. A. Williams,

48 M. J. Devos and A. Krief, Tetrahedron Lett., 1979, 1511. J. Chem. SOC., Perkin Trans. I , 1978, 1660.

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202 Organophosphorus Chemistry

ylide to give (44); the last intermediate can be isolated as its conjugate acid. On the basis of this Scheme, a horrific number of products are possible if two diflerent phosphonium ylides are used in the same reaction. However, the authors have managed to prepare (45) with different substituents on the double-bond from those on the cyclopropane ring by consecutive addition of two ylides under very specific conditions.43

A double Wittig reaction of (47) under conditions of high dilution has been used to synthesize (48) en route to l~thranidine.~~

il 6-Phosphorin4carbaldehydes (49) undergo normal Wittig reaction^.^^

R’R2C=CHCI I=CfICO,Me (46)

OMe OMe I \

+

147)

CHO I

(49)

+ Ph,P=CHAr

(48) 86%

CH-CHAr

__f Ph b P h

MCO’ ‘OMe

Ketones. The carbonyl-stabilized bis-ylide (50) has been used to prepare sym- metrical and unsymmetrical divinyl ketones by consecutive Wittig reactions (Scheme 13).46

(Ph,P=CH),CO

(50)

i’ ii 3 R~cH-cH C( O)C €I= CR’ R~

Reagents: i, RlR2CO; ii, R3CH0 Scheme 13

48 M. J. Devos and A. Krief, Tetrahedron Lett., 1979, 1515. 44 K. Fuji, K. Ichikawa, and E. Fujita, Tetrahedron Lett., 1979, 361. 45 K. Dimroth, H. H. Pohl, and K. H. Wichmann, Chem. Ber., 1979,112, 1272 413 H. J. Bestmann and W. Schlosser, Synthesis, 1979, 201.

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YIides and Related Compounds 203

Intramolecular Horner and Wittig reactions have been investigated as routes to cc &unsaturated y-Iactones (AaJ-b~tenolides).~~ The latter route (Scheme 14)

Scheme 14

is preferred since it can be achieved in very good yield under mild conditions. An intramolecular Wittig reaction has been used to prepare the first example of an optically active anti-Bredt compound (51), albeit in low yield.48

[a],, -259' (CHC1,)

a-Diketones undergo mono-olefination with Wittig reagents; for example, benzofurandiones (52; X= 0) and benzo[b]thiophen-2,3-diones (52; X= S) form (53 ; X = 0) and (53 ; X = S) on reaction with fl~orenylidenephosphorane.~~

Analogous reactions include syntheses of cis- and trans-7- [2-hydroxyethyl]- cephalosporanic acids (Scheme 15)b0 and precursors of 1 l-methyl- and 11,ll- dimethyl-prostaglandin (Scheme 16). 61

While p-isomers of the bicyclic ketone (54) react readily with methoxymethylene- phosphorane to give the alkene (59, a-isomers are stable under the same con- ditions; presumably due to a 1,3-steric e f f k ~ t . ~ ~ This specific behaviour has been used in the synthesis of various sesquiterpenes related to sativene (56).

47 S. F. Krauser and A. C. Watterson, jun., J. Org. Chem., 1978, 43, 3400. 48 M. Nakazaki, K. Naemura, and S. Nakahara, J . Chem. SOC., Chem. Commun., 1979,82. 49 M. M. Sidky and L. S. Boulos, Phosphorus Sulfur, 1978, 4, 299. 60 H. E. Applegate, C. M. Cimarusti, and W. A. Slusarchyk, Tetrahedron Lett., 1979, 1637. 5 1 K. Inoue, J. Ide, and K. Sakai, Bull. Chem. SOC. Jpn., 1978, 51, 2361. 53 M. Yanagiya, K. Kancko, and T. Kaji, Tetrahedron Lett., 1979, 1761.

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246 Compourzd

Organophosphorus Chemistry Comments* Ref.

Two crystal structures, with X = H 202 and COPh; ring has tub conformation in both cases. X = H , mean P-N(endo) 1.609(9) A; P-N(exo) 1.679(2) A X = COPh, mean P-N(endo) 1.595(4) A; P-N(exo) 1.655(2) A

Structures of two out of three 20 3 monoclinic modifications obtained at 110 K . (a ) boat-shaped ring

( b ) irregularly shaped ring mean P-N 1.549(5) A

mean P-N 1.546(5)R

* All structures were obtained by X-ray diffraction unless otherwise stated.

SO* H. P. Calhoun, R. T. Oakley, N. L. Paddock, S. J. Rettig, and J. Trotter, Can. J . Chcm.,

103 J. G. Hartsuiker and A. J. Wagner, J. Chem. SOC., Dalton Trans., 1978, 1425. 1978,56, 2833.

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Ylides and Related Compounds

R'C0,R2 + Ph,P=CHR3

205

J l , e C H R 3 ,A'HR3

CH,R-' R'COR3C=PPh, R C,oR2 R'C(

Scheme 17

A ~ ' O N ~ moR+ Ph,PO

(57)

unsaturated oxygen heterocycles have been prepared by intramolecular reactions of ylide-esters, e.g. (57). The stereochemistry and regiochemistry of Wittig reactions with substituted maleic anhydrides have been investigated5* and the results applied to the synthesis of methyl (Z)- and (E)-O-methylmulticolanates (Scheme 18). 69

Meo*cr+ H T

H Me0,C 1 3

Scheme 18

Carbonyl deactivation through phosphonium ylide substitution permits ring- contraction through intramolecular trapping of anions generated in charge- directed conjugate addition reactions, as exemplified in Scheme 19.60 Diazo- azoles react with various ylides and eliminate phosphine to give triazoles (58)."l

Reagent: i, PhsP=CHCOzMe

( 5 8 )

58 D. W. Knight and G. Pattenden, J. Chem. SOC., Perkin Trans. 1 , 1979, 62. 5s D. R. Gedge and G. Pattenden, J . Chem. SOC., Perkin Trans. 1 , 1979, 89. 60 M. P. Cooke, jun., Tetrahedron Lett., 1979, 2199. 61 G. Ege and K. Gilbert, Tetrahedron Lett., 1979, 1567.

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206 Organophosphorus Chemistry

,COCH=PPh,

J CH zyCOC H=fPh,

‘ “ 2 ) , A N u

Scheme 19

Quinquevalent phosphorus adducts are obtained from unstabilized phos- phonium ylides on treatment with oxiran (under mild conditions) and oxetan (under forcing conditions) (Scheme 20).62

Scheme 20

Phosphonium ylides and carbon disulphide form adducts (59), which, if they possess a-hydrogen, undergo proton transfer and further reaction with the starting ylide to give the phosphonium salt-ylide Alkylation of (60) gives a thioester-stabilized ylide (61), which can be further alkylated but does not undergo

the Wittig reaction. Pyrolysis of thioacylalkylidenephosphoranes (62) provides a new synthesis of substituted thiophens (Scheme 21).64 l-Substituted vinyl- phosphonium salts have been prepared by the reaction of imminium salts with

62 H. Schmidbaur and P. Hoel, Chem. Ber., 1979,112, 501. 8s H. J. Bestmann, R. Engler, H. Hartung, and K. Roth, Chem. Ber., 1979,112,28. 64 H. J. Bestmann and W. Schaper, Tetrahedron Lett., 1979, 243.

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Ylides and Related Compounds 207

R1C-cR2iPh, , -& II S

(62) /Ph$S

R' 40-75%

Scheme 21

phosphonium ylides (Scheme 22) and used in cyclopentanone synthesis.66 Phosphonium ylides may be mono- or di-selenated with phenylselenyl bromide; oxidative deselenation leads to vinylphosphonium salts.66

SPh + I

Ph$=CHSPh + CH,=GMe, X- __t Ph,P-C-CH, X'

Scheme 22

Hexaphenylcarbodiphosphorane reacts with phthalic anhydride to give the betaine (63), which on methylation gives the acetylenic salt (64) and on heating eliminates phosphine oxide to give the ylide (6Q6' Unsymmetrical carbodi- phosphoranes (66) undergo thermal rearrangement to phosphine-substituted ylides (67).68 These ylides are preferentially protonatedat carbon, but preferentially

+

Ph CH,R (66)

I

CHPhR (67)

65 A. T. Hewson, Tetrahedron Lett., 1978, 3267. *6 G. Saleh, T. Minami, Y. Ohshiro, and T. Agawa, Chern. Ber., 1979,112, 355. 97 H. J. Bestmann and W. Kloesters, Tetrahedron Lett., 1978, 3343. 68 R. Appel and G. Erbelding, Tetrahedron Lett., 1978, 2689.

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208 Organophosphorus Chemistry

methylated at phosphine-phosphorus. The 1,2-diphosphacyclopent-5-ene (68) is thermally unstable even at room temperature, and eliminates isobutene to give (69).68 More surprising are the reactions of (68) with alcohols, acids, and amines to give (70) with elimination of isobutane.

OBu' Ph I P-P-Ph

0 0 Ph 11 P-P-Ph

(But O . Q F x R C0,Bu'

0

Ph I! Cb,Bu'

(70)

g (But 0202

(69)

A variety of ylide complexes with transition metals, including Ni,70 C0,7l and have been prepared.

3 Reactions of Phosphonate Anions PO-Activated olefin synthesis has been reviewed,78 and it is interesting to note that phosphonate anions seem capable of protecting themselves against com- petition from alternative olefin syntheses.74

The important development of olefination with five-membered cyclic phos- phonates, which allows the synthesis of significant proportions of (Z)-olefin~,~~ is now followed by n.m.r. evidence for the intermediacy of an oxaphosphetan, e.g. (71), in these reaction^.^^ This is welcome since, unlike the Wittig reaction, detailed mechanistic studies of the Horner reaction have been neglected.

0-

(7 1)

6Q H. J. Padberg, J. Lindner, and G. Bergerhoff, J. Chem. Res. (S) , 1978, 445. 70 W. Malisch, H. Blair, and S. Voran, Angew. Chem., Int. Ed. Engl., 1978, 17, 780. 7 1 N. L. Holy, N. C. Baenziger, and R. M. Flynn, Angew. Chem., Int. Ed. Engl., 1978,17,686. 72 W. Scharf, D. Neugebauer, U. Schubert, and H. Schmidbaur, Angew. Chem., Int. Ed.

73 W. S. Wadsworth, jun., in 'Organic Reactions', ed. W. G. Dauben, John Wiley and Sons,

74 E. Vedejs, J. M. Dolphin, and W. T. Stolle, J. Am. Chem. SOC., 1979,107,249. 7 5 D. J. H. Smith, in 'Organophosphorus Chemistry', ed. S. Trippett (Specialist Periodical

713 E. Breuer, S. Zbaida, and E. Segall, Tetrahedron Lett., 1979, 2203.

Engl., 1978, 17, 601.

New York, 1977, Vol. 25, p. 73.

Reports), The Chemical Society, London, Vol. 10, p. 222.

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Ylides and Related Compounds 209

Further detailed studies of the reaction of enones with phosphonate carbanions have been

Two new phosphonates (72) and (73) have been investigated as synthons for en01 ethers, and hence for aldehyde homologation (Scheme 23).78 Reagent (72) is preferred, and appears to overcome the problems previously associated with the synthesis of enol ethers by the Wittig and Horner reactions. Homologous ketones or aldehydes can also be obtained through reaction with the carbanion of the imine-substituted phosphonate (74) (Scheme 24).79 A convenient one-pot procedure for the synthesis of a &unsaturated aldehydes from N-t-butyl- ethylideneimine (75) without isolation of the intermediate phosphonate has been reported (Scheme 25).B*

punsaturated ketones have been synthesized in high yields by standard olefination with ketals of /?-diphenylphosphinoyI ketones (76).81 A new, general

0

(72) R2 = THP (73) R2'= CH,CH,OMe

Reagents: i, LiNPA; ii, RSRQCO; iii, either A or Hso+ and then KOBut

Scheme 23

0 /R'

(EtO),PCHR'N=CHPh ,> R'R2C=C, I1 '* ii

N:

i, iii. i vL ,,,,HE

Reagents: i, BuLi; ii, RIRZCO; iii, E+; iv, H30+

Scheme 24

(7 5 ) 53-94%

0 II

Scheme 25

Reagents: i, LDA, at -78 "C; ii, (Et0)zPCl; iii, RlRZCO; iv, H30+

77 B. Deschamps, Tetrahedron, 1978, 34, 2009. 78 A. F. Kluge, Tetrahedron Lett., 1978, 3629. 79 S. F. Martin and G. W. Phillips, J. Urg. Chem., 1978, 43, 3792. 80 A. I. Meyers, K. Tomioka, and M. P. Fleming, J. Urg. Chem., 1978, 43, 3788. 81 A. Bell, A. H. Davidson, C. Earnshaw, H. K. Norrish, R. S. Tom, and S. Warren, J . Chem.

SOC., Chem. Commun., 1978,988.

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210 Organophosphorus Chemistry synthesis of keten SS- and OS-thioacetals (but not keten acetals) from the phosphonates (77) is available.82 The 9-heteronia-anthracephosphonates (78) undergo normal olefination with aryl or conjugated aliphatic (but not with saturated aliphatic) aldehydes and ketones.8s

(77) x = 0 or s (78) X = NR, 0, or S

l-Phenylthio-butadienes, increasingly used in Diels-Alder reactions, are conveniently prepared via 3-phenylthioallylphosphine oxides (Scheme 26).** (E,Z)- 2,CDecadienoic acid, containing < 2% of the (E,E)-isomer, has been prepared by the reaction of hex-2-ynal with triethyl phosphonoacetate carbanion followed by Lindlar reduction (Scheme 27).86 Polyene synthesis using allylphosphine oxide carbanions has been investigated.86 In almost all cases the stereochemistry of double bonds in the carbonyl compound and in the phosphine oxide is preserved.

0 II

0 0 I I

Ph?PCR'=CHCH,SPh + Ph,PCHR'CH=CHSPh PhPCHR'CH-CH, + ll

Reagents: i, BuLi; ii, PhzSz; iii, RZCHO.

Scheme 26

0 II

(E tO),PCH,CO,Et jeiii +

(30,E t

Reagents: i, NaH, THF; ii, Me(CHz)4=CHO; iii, Lindlar catalyst, Hz.

Scheme 27

M. Mikolajczyk, S. Grzejszczak, A. Zatorski, B. Mlotkowska, H. Gross, and B. Costisella, Tetrahedron, 1978,34, 3081.

88 K. Ishikawa, K. Akiba, and N. Inamoto, Bull. Chem. SOC. Jpn., 1978, 51, 2684. 84 P. Blatcher, J. I. Grayson, and S. Warren, J. Chem. SOC., Chem. Commun., 1978, 657. 85 G. Rickards and L. Weiler, J. Org. Chem., 1978,43, 3607. 16 J. M. Clough and G. Pattenden, Tetrahedron Lett., 1978,4159.

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Ylides and Related Compounds 21 1

The stereospecific (E)-olefination is due to the higher rate of decomposition of threu-intermediate (79), as compared to erythro-intermediate (80), as demon- strated by the isolation and separate decomposition of (79) and (80).

(79) R' = OH, R2 = H (80) R' = H , R2 = OH

Treatment of the phosphonate aldehyde (81) with base at high dilution leads directly to the cyclic dimer (82), and so provides a synthesis of (-)-vermiculine (83).87

NPH THF

(82) X = O(CH,),O, Y = S(CH,),S (83) Y = X = 0

Attempts to prepare various ester analogues (85) of pseudomonic acid (86) by the reaction of the ketone (84) with ester-stabilized phosphonate carbanions were only partially Similarly, attempts to prepare the parent acid of (85) by reaction with PP-diethyl phosphonoacetic acid dianion (87) were un-

0 R'+i ,EtO,B - CHC0,R' ~

R'COMe C0,R2 (84) Me

( 8 5 ) R2 = alkyl (86) R2 = (CH,),CO,H

(EtO), 3 --CHCO; R' = Me w OH 0 L Ho6-+ (87)

87 K. F. Burri, R. A. Cardone, W. Y. Chen, and P. Rosen, J. Am. Chem. Soc., 1978,100,7069 88 J. P. Clayton, K. Luk, and N. H. Rogers, J. Chem. Sac., Perkin Trans. 1. 1979. 308.

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212 Organophosphorus Chemistry

productive, although the latter reagent reacted with cyclohexanone to give a quantitative yield of cyclohexylideneacetic acid.

The carbanions of phosphonamides (88) and (89) react with electrophilic reagents to give products which, theoretically, derive from the anions (91) and (92).*# In the case of the allylic carbanions (90) and (93)90 the reactions are regio- specific, giving y-adducts in almost every case. Attempts to use the dianion (94) met with limited success, due to preferential O-alkylation. The silylmethyl- phosphonate (95) is a novel source of methylene ylide, and reacts with ketones, probably via (96), to give terminal 01efins.~~

0

RC- I I

0 0 II

RC--P(NMe,), BuLi * I1 Et,SiOP(NMe,), RCHo * RyHP(NMe,l,

I RCH=CHCHO OSiEt, I (88)

I OSiEt, (91)

OSiEt, ( 8 9 )

0 II

R'CH=CHq--P( OE t ), I

OSiMe, 0 II

R*x P R'RZCHCH=C-P(OEt), I

0 II

R'CHCH=C-P(OE t)l I OSiMe,

(93)

OSiMe, 0 R T P ( N M e * ) * I1

0- (94)

0 I1

Me,SiCH,P(OMe), -+ R'R'Co t R'RT=CH,

( 9 5 ) (96)

Both 8-valerolactone and y-butyrolactone react with one equivalent of diethyl cyanomethylphosphonate carbanion, but not with triethyl phosphonoacetate carbanion, to give mixtures of isomeric olefms as the major products (Scheme 28).#% The reactions of the a-phosphono-y-butyrolactone carbanion (97) with $9 D. A. Evans, J. M. Takacs, and K. M. Hurst, J. Am. Chem. SOC., 1979,101,371. 90 T. Hata, M. Nakajima and M. Sekine Tetrahedron Lett., 1979, 2047. 91 A. Sekiguchi and W. Ando, Chem. Lett., 1978, 1385. 93 A. J. Duggan, M. A. Adams, P. J. Brynes, and J. Meinwald, Tetrahedron Lett., 1978,4323.

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Ylides and Related Compounds 213

ti 0 0 or 1 Scheme 28

anhydrides, epoxides, carbonates, and lactones have been inve~tigated.~~ A variety of pathways are followed, including olefination and formation of a spiro-lactone. Epoxides generally undergo ring-opening, but epoxy-ketones react selectively at the carbonyl group to give epoxy-alkenes (98) in good yield.

1 -Nitroalkyl-phosphonates have been prepared in moderate yield by nitration of phosphonate ~arbanions .~~

(97) 0 (98)

4 Selected Applications in Synthesis Pheromones.-The Wittig reaction appears to be a source of racemization in the synthesis of ipsdienol (99) and ipsenol (lOO), the pheromones of the ponderosa pine beetle.ab

Bestmann has shown that (E,E)-1,3-dienyl-phosphonates can be reduced stereospecifically to the corresponding (E,E)-1 ,4-dienes with removal of the phosphonate group (Scheme 29);9s this is a potentially useful reaction in pheromone synthesis.

Scheme 29

99 T. Minami, M. Matsumoto, H. Suganuma, and T. Agawa, J. Org. Chem., 1978,43, 2149. 94 H. Feuer, W. D. Van Buren, jun., and J. B. Grutzener, J. Org. Chem., 1978,43,3676. 95 K. Mori, T. Takigawa, and T. Matsuo, Tetrahedron, 1979, 35, 933. 96 H. J. Bestmann, J. Suss, and 0. Vostrowsky. Tetrahedron Lett.. 1979. 245.

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214 Organophosphorus Chemistry

The trifluoromethyl analogues (101) and (102) of juvenile hormone JH-I11 have been prepared by combinations of ylide and phosphonate olefinations, although the syntheses are not without their problems.g7

(101) .R' = Me, R2 = CF, (102) R' = CF,, R2 = Me

Wittig reactions of the lactols (103) and (104) have been used to prepare (+)- and (- )-disparlure (105), the gypsy moth pheromone.B* The key step in a synthesis of the sexpheromone(l07) of Orgyiupseudotsugata is the conversion of 2-hydroxy- tetrahydropyran into (Z)-undec-5-en-l-ol (106) with 98 % stereospecificity by a

OH. + Ph,P=CH(CHJ6Me THPO"

THPO

-*\

THPO"

OH + Ph$--CHCH,CHMe,

1

Wittig reaction at - 70 "C in THF, using potassium t-butoxide as base (Scheme 30).gg Predictably, higher temperatures and the use of butyl-lithium as base gave larger amounts of the (E)-isomer.

The silazide technique [the use of sodium bis(trimethylsily1)amide as the base for ylide generation] has been used to synthesize (2)-7-dodecenyl acetate (108),

97 F. Camps, R. Canela, J. Coll, A. Messeguer, and A. Roca, Tetrahedron, 1978, 34, 2179. 9% K. Mori, T. Takigawa, and M. Matsui Tetrahedron, 1979. 35, 833. 99 M. Fetizon and C. Lazare, J. Chem. SOC.. Perkin Trans. 1, 1978, 842.

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YIides and Related Compounds 215

0"" A C5H\

g4 steps OH

0 (107)

Reagents: i, Ph3P=CHGH11, at - 70 "C, THF

Scheme 30

(Z)-7-tetradecenyl acetate (1O9),lo0 and (Z)&decenyl acetate (1 10)lo1, which is the recently identified pheromone of the male turnip moth.

H H I 1

.OW(CH,),CO,Et + Me(CH,),, CH=PPh, --+ Me(CH,),, C=C(CH,),CO,Et

MdCH,),, C=C(CH,),OCOMe

(1'0s) II = 3 (109) I I = 5

H H I I Me(CH,),CHO + Ph,P=CH(CH,),CH=CH, - Me(CH,),C=C(CH,),CH=CH,

H H I I

Me(CH,),C=C(CH,),OCOMe

(1 10)

Codlemone (1 1 1),lo2 (Z)-8-,dodecenyl acetate (1 12),lo5 and the sex pheromone (113) lo4 of the female red bollworm moth have all been synthesized via the Wittig reaction. Prostaglandins.-A potential complication in the standard method for construc- tion of a side-chain, using the reaction of 4-carboxybutyltriphenylphosphorane with the lactol (114), is migration of the silyl group to give (115) and (116).lo6

100 H. J. Bestmann, K. H. Koschatzky, and 0. Vostrowsky, Chem. Ber., 1979, 112, 1923. lo1 H. J. Bestmann, 0. Vostrowsky, K. H. Koschatzky, H. Platz, T. Brosche, I. Kantardjiew,

M. Rheinhold, and W. Knauf, Angew. Chem., Znt. Ed. Engl., 1978,17, 768. lo2 H. J. Bestmann, J. Suss, and 0. Vostrowsky, Tetrahedron Lett., 1978, 3329. lo3 J. H. Babler and M. J. Coghlan, Tetrahedron Lett., 1979, 1971. lo4 R. H. Wollenberg and R. Peries, Tetrahedron Lett., 1979, 297. lo5 Y. Torisawa, M. Shibasaki, and S. Ikegami, Tetrahedron Lett., 1979, 1865.

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216 Organophosphorus Chemistry

MeCH=CHCH=CH(CH2),0H 'Me(CH,),CH=CH(CH,),CH,OCOMe (111) (112)

H,C=CHCH = CH (CH,),,OCOM e

(1 13)

OH I

Bu'Me,SiO

Ph,P=CH (CHJ,CO,R

(115) R' ,= OSiMe,Bu', R2 = H (116) R' = I I , it2 = OSiMe,But

The rate of the Wittig reaction with lactol(ll7) is dependent on the nature of the substituent R1.lo6

Amongst the prostaglandin analogues prepared is the bioactive carbocyclic analogue (1 18) of prosta~yc1in.l~~

R" CO,H (117)

Ph,P=CH (CH,),CO,-

HO= I

bH (118)

HO= OH

Carbohydrates.-Long-chain carbohydrates lo8 0 Io9 and undecoses, e.g. (1 20),1O* have been prepared with retention of configuration from the protected galactose 6-phosphorane (1 19) and the appropriate aldehyde.

l06 I. T6moskozi, G. Galambos, G. Kovacs, and L. Gruber, Tetrahedron Lett., 1979, 1927. lo' K. C. Nicolaou, W. J. Sipio, R. L. Magolda, S. Seitz, and W. E. Barnette, J . Chem. SOC.,

108 A. Sekiguchi and W. Ando, J . Org. Chem., 1979,44,413. 1OQ J. A. Secrist, tert., and S.-K. Wu, J. Org. Chem., 1979, 44, 1434.

Chem. Commun., 1978, 1067.

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Ylides and Related Compounds 217

Me

+ O H W M e 0 0 .

X Me Me Me

Carotenoids.-The stereospecific synthesis of ( k )-trisporol B (1 22), a prohormone of Blakeslea trispora, has been accomplished by a Wittig reaction of the (2)- phosphonium salt (1 21) (Scheme 31).110 Unfortunately, the ylide derived from (121) undergoes isomerization to the (E)-form, and the product is a 1 : 1 mixture of (122) and its (E)-isomer. Short reaction times increase the proportion of (2)-isomer to > SO%, but at the expense of yield.

('121) Br-

Scheme 31

Reactions of the fluorinated ester phosphonates (123) and (124) with the appropriate aldehyde and ketone have been used to prepare 10-fluoro- (125) and 14-fluoro-retinol (1 26) and several geometric isomers. ll1

0

(E t 0 ),PCH R' R2 II (125) R' = F, R2 = H (126) R1 = H , R2 = F /F

(123) R' = F, RZ = CO,R (124) R' = H , R2 = ,C=C

Me 'CO,R

110 M. P. Prisbylla, K. Takabe, and J. D. White, J. Am. Chem. Sac., 1979, 101,762. 111 A. E. Asato, H. Matsumoto, M. Denney, and R. S. H. Liu, J. Am. Chem. Soc., 1978,100,

5957.

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21 8 Organophosphorus Chemistry

Wittig reactions of diene ylides, e.g. (127), have been used to synthesize (+)- azafrin (128) and its retinoate and @-carotene analogues.11s

&;\&cH=pph3 & $ L + y V o 2 H

'OH *'OH (127) (128)

Non-benzenoid Aromatic Compounds.-W i t t ig react ions with propargylidene- phosphorane and 2,5-bis-(2-formylvinyl)furan have been used to prepare (1 29), as a mixture of isomers, en route to dehydro-annu1enes.llS

Bis-phosphonium ylides (130), (131), and (132) have been used in the synthesis of benzannulated [9]- and [13]-annulenes, and hence their anions.l14

+ +

Ph,PCH,C=CH

Br-

112 M. Akhtar, A. E. Faruk, C.4. Harris, G. P. Moss, S. W. Russell, and B. C. L. Weedon,

1la H. Ogawa, J. Makae, Y. Taniguchi, and H. Kato, Tetrahedron Lett., 1978, 4929. 114 M. Rabinovitz, 1. Willner, A. Gamliel, and A. Gait, Tetrahedron, 1979, 35, 667.

J . Chem. SOC., Perkin Trans. I , 1978, 1511.

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