y t y \ , ^ s ^ | S S N . 0 Q 1 6 _ 5 6 Q 3

GCIT A21, 373-423 Vol. 121, No. 8, August, 1991

GAZZETTA CHIMICA . ^ j o ITALIANA An International Journal of Chemistry

Published by Societä Chimica Italiana Viale Liegi 48, 00198 Roma, Italy

GAZZETTA CHIMICA IT ALIANA an International Journal of Chemistry

published by Societä Chimica Italiana, Viale Liegi 48, 00198 Roma, Italy

E d i t o r :

Fausto CALDERAZZO, Universitä di Pisa

E d i t o r i a l B o a r d : Angelo ALBERTI, C.N.R., I.Co.C.E.A., Ozzano E., Bologna Roberto AMBROSETTI, C.N.R., I .C.Q.E.M., Pisa Enr i co BACIOCCHI, Universitä d i Roma Paolo BELTRAME , Universitä di Mi lano Giancar lo BERTI , Universitä d i Pisa Claudio BIANCHINI, C.N.R., I.S.S.E.C.C., Firenze Sergio CABANI, Universitä d i Pisa Lu i g i CASSAR, Italcementi S.p.A., Bergamo Mar i o CIAMPOLINI, Universitä d i Firenze Paolo CORRADINI, Universitä d i Napol i Alessandro DONDONI, Universitä d i Ferrara Mar i o FARINA, Universitä di Mi lano Barbara FLORIS, II Universitä di Roma Marco FoÄ, H imont Italia, Centro Ricerche, Novara Dante, GATTESCHI, Universitä d i Firenze Alberto GHIRLANDO, Universitä di Parma Mauro GRAZIANI, Universitä d i Trieste G ino LUCENTE , Universitä di Roma Claudio LUCHINAT, Universitä d i Bologna Ugo MAZZUCATO, Universitä di Perugia Mar i o NARDELLI, Universitä d i Parma Gian luca NASINI, C.N .R., Centro S.S.O.N., Pol . d i Mi lano Piero PAOLETTI, Universitä di Firenze Mar i o PIATTELLI, Universitä d i Catania Ugo ROMANO, En iChem Synthesis, Mi lano Raffaello ROMEO , Universitä d i Messina Renzo Rossi , Universitä di Pisa Annalaura SEGRE , C.N .R., I.S.C., Monterotondo, Roma Maur i z i o SPERANZA, Universitä della Tuscia, Viterbo Giuseppe TAGLIAVINI, Universitä di Padova Jacopo TOMASI, Universitä d i Pisa Adolfo ZAMBELLI, Universitä d i Salerno Pier ino ZANELLA, C.N .R., I.C.T.R., Padova

A d v i s o r y B o a r d : Howard ALPER, University of Ottawa Vincenzo BALZANI, Universitä di Bologna Maur i z i o BRUNORI, Universitä d i Roma Alessandro CIMINO, Universitä d i Roma Vi t tor io CRESCENZI, Universitä d i Roma Pierre DDCNEUF, Universite de Rennes A lan R. KATRITZKY, University of Flor ida W i lhe lm KEIM , Rheinisch-Westfälische Technische

Hoschschule Aachen Jean-Marie LEHN , Universite de Strasbourg Frieder LICHTENTHALER, Techn. Hochschule Darmstadt Peter MAITLIS, University of Sheffield Läszlö MARKO, Hungarian Acad. of Sciences Veszprem Lu i g i MINALE , Universitä di Napol i I lya I. MOISEEV, Academy of Sciences, Moscow Fernando MONTANARI, Universitä d i Mi lano He inr i ch NOETH , Universität München and C h e m . B e r . George A. OLAH , University of Southern Cali fornia Wolfgang VON PHILIPSBORN, Universität Zürich Jacqueline SEYDEN-PENNE , Universite de Paris Sud

and B u l l S o c . C h i m . Fr. Malco lm G .H . WALLBRIDGE, University of Warwick and

/. C h e m . S o c , D a l t o n Trans. Helmut WERNER , Universität Würzburg

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GAZZETTA CHIMICA ITALIANA, Vol. 121, No. 8, August 1991

C O N T E N T S

Research Report

HERBERT MAYR, JANUSZ 3 , 3 , 4 , 4 , 5 , 5 - h e x a m e t h y l - l , 2 - b i s ( m e t h y l e n e ) c y -BARAN and ULRICH W . H E I G L clopentane: a novel probe for the study of cy-

cloaddition mechanisms 373

Articles

LUISA BENATI, PIER CARLO Boron trifluoride-promoted reaction of p-nitro-MONTEVECCHI and PIERO benzenesulphenanilide w i th alkynes. A further SPAGNOLO insight into the reactivity of the resulting th i i r en ium

ion intermediates 383

ALBERTO ARNONE, GLANLUCA Isolation and structure elucidation of doremone A , NASINI, ORSO VAJNA DE PAVA a new spiro-sesquiterpenoidic chroman-2,4-dione and LORENZO CAMARDA from ammoniac gum resin 387

ANGELO LIGUORI, GIOVANNI Competitive formation of tetrahydro-1,3-oxazines by ROMEO, GIOVANNI SINDONA isoxazol idinium salts ring-opening react ion 393 and NICOLA UCCELLA

SULTAN ABU-ORABI, ADNAN Dipolar cycloaddition reactions of organic bis-azides ATFAH, IBRAHIM JIBRIL, w i th some acetylenic Compounds 397 FAKHRI MARII and AMER A L -SHEIKH ALI

FABIO BENEDETTI, SILVANO Reactivity of secondary functionalized enamines BOZZINI, SILVANA FATUTTA, towards electrophilic diazenes 401 MIRELLA FORCHIASSIN, PATRI-ZIA N l T T I , G l U L I A N A P l T A C C O , and CLAUDIO RUSSO

LIBERATO CARDELLINI, LUCE - Single electron - transfer. Reactions of indo l inon ic DIO GRECI, JOHN M . TEDDER aminoxyls wi th d iazonium salts . 407 and JOHN C. WALTON

RINALDO POLI and B E T H E . Synthesis and structure of b is ( l ,2-bisdiphenyl-OWENS p h o s p h i n o e t h a n e ) h e x a h a l o d i m o l y b d e n u m ( I I I ) ,

Mo 2 X 6 ( dppe ) 2 (X=C1, B r , I) . 413

Communication

LORENZO DE NAPOLI, DANIELA Synthesis of cyclic branched ol igodeoxyribonu-MONTESARCHIO, GENNARO cleotides . 419 P l C C I A L L I , C l R O S A N T A C R O C E and ANNA MESSERE

Additions and corrections 423

Gazzetta C h i m i c a I t a l i a n a , 121, 1991 — Pub l i shed by Societä C h i m i c a I tal iana 373

RESEARCH REPORT

3,3,4,4,5,5-HEXAMETHYL-1,2-BIS(METHYLENE)CYCLOPENTANE: A NOVEL PROBE FOR THE STUDY OF CYCLOADDITION MECHANISMS (*)

HERBERT MAYR (°), JANUSZ BARAN and ULRICH W . HEIGL I n s t i t u t für C h e m i e , M e d i z i n i s c h e Universität zu Lübeck, R a t z e b u r g e r Allee 160, D - 2 4 0 0 Lübeck 1, G e r m a n y

S u m m a r y — 3,3,4,4,5,5-hexamethyl-l,2-bis(methylene)cyclopentane, 1, w h i c h is readi ly accessible v i a electrophil ic acylat ion and a lky lat ion reactions, incorporates a p lanar s-cis-fixed 1,3-diene system, the non­terminal posit ions of w h i c h are sterically shielded. Therefore, Compound 1 shows a relatively great tendency to undergo 1,4-additions instead of 1,2-additions. W i t h dihalocarbenes, a 1,2 over 1,4 adduct rat io of only 2.3-2.7 is observed, and diphenylketene undergoes (4+2)-cycloadditions across the C C - and the C O - double bond. Therma l , non-catalysed d imer isat ion of 1 gives a mixture of [4+2]- and [4+4]-cyclodimer, both products ar is ing through intermediate d iradicals . The react ion of 1 w i th 1,3-diphenylazal ly l l i thium affords the [4+3]-cycloadduct 12 as the m a i n product. Benzoni t r i l e oxide and 1 combine w i th format ion of the regulär [3+2]-cycloadduct 15 and the oxime 16, w h i c h are explained through intermediate d iradicals . C,N-Diphenyln i t rone reacts w i th 1 and other 1,3-dienes to give the ord inary [3+2]-cycloadducts (e.g. 21, 22) as wel l as the [4+3]-cycloadducts 26 and 29-31, again ind icat ing the intermediacy of d iradicals . Possibi l i t ies to use 1 as a probe for concertedness are discussed.

I N T R O D U C T I O N

Addi t ion reactions to 1,3-dienes can lead to the formation of 1,2- and/or 1,4-adducts (scheme l ) y .

S C H E M E 1

S C H E M E 2 - 1,3-DIENES USUALLY G IVE 1,2-ADDUCTS WITH C A R B E N E S , K E T E N E S , A L L Y L ANIONS, 1,3-DIPOLES AND 1,3-DIENES

*2

+ A — B C X 2 \ ' R 2 C = C = 0

A 1,2-adduct

A 1,4-adduct

If A -B represents a cycloaddit ion partner, one of the two reaction modes is usually highly preferred. Dienophiles, for instance, l ike maleic anhydride, acrylates, etc., undergo 1,4-additions and lead to the formation of cyclohexenes (Diels-Alder reaction) 2 . Carbenes, ketenes, al lyl and azallyl anions as wel l as 1,3-dipoles and related reactants generally add to a

n 2 unit of the 1,3-diene3, thus exhibit ing a strong preference for 1,2-addition (scheme 2). Whi le 1,4-additions of carbenes and ketenes are orbital symmetry allowed processes, the corresponding reactions of al lyl anions, 1,3-dipoles, and 1,3-dienes represent ( ^ s + TC4s) processes, and are therefore thermally forbidden reactions 3 .

Assuming that less than 0.5% of side products are not usually detected dur ing conventional product analyses, the failure to observe 1,4-adducts i n reactions of 1,3-dienes w i th the cycloaddit ion partners shown i n scheme 2 indicates the activation energies for the 1,4-additions to be at least 3 kcal

m o H higher than those of the observable 1,2-additions. It is of theoretical interest to learn whether the barrier for the elusive 1,4-additions is just slightly greater (-3-5 kcal m o H ) than that for the observed 1,2-additions or whether there is a huge difference between the activation energies of the two processes (scheme 3).

S C H E M E 3 - H O W BAD A R E 1,4-ADDITIONS? W H A T IS T H E BARRIER FOR 1,4-ADDITIONS?

AE a >3 kcal mol"1

(*) Dedicated to Professor Jürgen Sauer on the occas ion of his 60th bir thday. Lecture presented at the VT Conference o n Pract ice andTheory of Per icyc l ic React ions, Firenze, Italy, M a y 24-25,1990.

(°) To w h o m correspondence should be addressed.

374 H . Mayr, J. B a r a n a n d U. W. H e i g l

There are two ways to improve the chance of observing 1,4-additions: One can either make the 1,4-additions more attractive by f ixing the 1,3-diene i n an s - c i s conformation, or one can retard the 1,2-additions by attaching bulky substituents at C-2 and C-3 of the 1,3-diene (scheme 4).

S C H E M E 4

1,4-additions are favoured i n s-c/s-fixed dienes

cndocyclic exocyclic n = 1,2 n = 1,2,3

1,2-additions are retarded by bulky groups i n 2- and 3-posit ion

The title Compound 1 incorporates both features, and is, therefore, an ideal candidate for 1,4-additions (scheme 5).

S C H E M E 5

Facile approach possible (^4)

Sterically hindercd (K2)

S Y N T H E S I S A N D P R O P E R T I E S O F T H E T I T L E C O M P O U N D

Several years ago we have elaborated an efficient access to highly substituted cyclopentenes v i a [3++2]-cycloaddit ion reactions (scheme 6). Hexa- to octa-methyl-substituted cyclopentenes have been synthe-sised by the ZnCl 2 -catalysed reaction of allyl chlorides wi th a lkenes l

S C H E M E 6 - C Y C L O P E N T Y L CATIONS via [3 + +2 ] -CYCLOADDITIONS O F A L L Y L CATIONS WITH A L K E N E S

This reaction type is the key-step i n the synthetic sequence outl ined i n scheme 7, wh ich is self-explanatory. Octamethylcyclopentene, 2, is the only intermediate of this sequence, wh ich has been purif ied; it is obtained i n 58% yield from acetyl chloride and trimethylethylene 5 . A less favourable access to the intermediate tetramethylallyl alcohol, wh ich we had elaborated i n the ini t ia l period of this project^, has recently been published by Lambert and Z iemnicka-Marchant 6 . Brominat ion of 2 does

not yield an addit ion product (sterically shielded double bond!), but wi th excess bromine at room temperature the bisal lyl bromide 3 is generated selectively 7. Treatment w i th magnesium yields the title Compound 1 i n 62% yield from 25.

S C H E M E 7 - SYNTHESIS O F H E X A M E T H Y L - 1 , 2 - B I S ( M E T H Y L E N E ) C Y C L O -P E N T A N E

3 1

The structurally related 3,3,6,6-tetramethyl-l,2-bis(methylene)cyclohexane can be synthesised i n only 3 steps by the sequence shown in scheme 85»9.

S C H E M E 8

The spectroscopic properties of 1 are not ab­normal . Its UV -max imum is almost identical to that of the non-methylated l,2-bis(methylene)cyclo-pentane, and the slight lowering of the ionisation Potential by the methyl groups can be attributed to CC-hyperconjugation (scheme 9 ) J 0 > n . Analogous effects by branching i n al lyl ic posit ion have been observed i n the photoelectron spectra of acyclic a lkenes 7 2 .

S C H E M E 9 - COMPARISON OF U V - AND P E - SPECTROSCOP IC D A T A 7 0 ' 7 7

W " m ) 250 246

IPV.i(eV) 8.73 8.4

Neat 1 can be stored for months at <5 °C in a nitrogen atmosphere. When a drop of it is exposed to atmospheric oxygen at ambient temperature for 24 h, crystals grow out of the l i qu id wh i ch have been identified as an ol igomeric peroxide w i th ! H N M R singlets at 6 0.88, 1.10 and 4.72 ppm, and 1 3 C N M R resonances at 8 21.27 (q), 24.72 (q), 46.69 (s), 49.45 (s), 67.83 (t) and 142.64 ppm (s)9.

S C H E M E 10

Study of c y c l o a d d i t i o n m e c h a n i s m s 375

Compound 1 undergoes normal Diels-Alder reactions w i th dienophiles. The relative reactivities, given i n scheme 11, show that the methyl groups i n 1 exert only a smal l influence on the 1,4-reactivity of l 7 7 .

S C H E M E 11 - A T T A C K TO T H E T E R M I N A L M E T H Y L E N E GROUPS O F T H E 1,3-DIENE IS ONLY SL IGHTLY A F F E C T E D BY T H E M E T H Y L SUBSTITUENTS

CH3O2C CO2CH3

C H 3 O 2 C — CO2CH3

* H /*CH 3 =0.14

CH3O2C CO2CH3

*H/*CH 3= 9.1 3

CH3O2C H

H CO2CH3

CARBENES

1,3-dienes usually react w i th singlet carbenes i n a 1,2-fashion to give v inylcyclopropanes 7 3 . Homo-1,4-additions to norbornadiene 7 4 and intramolecular 1,4-additions i n the synthesis of benzvalenes 7 5 are among the few cases, wh i ch show a different reactivity pattern. Bickelhaupt observed 1-3% of 1,4-adducts i n reactions of dichlorocarbene to 1,2-bismethylenecycloalkanes (ring size 5-8) and 4-19% of 1,4-adducts i n the corresponding reactions of dibromocarbene 7 6 . Scheme 12 shows that the ratio (l,4-/l,2-adducts) is considerably increased by adding methyl groups. Assuming the rate of the 1,4-additions to be unaffected by the methyl groups, one can derive that the methyl groups raise the barriers for the 1,2-additions by 1.5-1.7 kcal m o H , w i th the consequence that 1 gives the highest proport ion of 1,4-adduct i n intermolecular carbene additions reported up to now 7 7 .

S C H E M E 12 - COMPETING 1,2- AND 1,4-ADDITIONS O F C A R B E N E S

x x

:CX ,

A A

cC -cxx x = a

X = Br 2 4

Bickelhaupt et al, 1985

Lambert et a l 6 investigated the reaction of 1 w i th C B r 2 (from P h H g C B r 3 ) at different diene con-centrations and found the product ratio to be

independent of the concentration of l . T h i s Observation Supports the assertion that the 1,4-adducts, l ike the 1,2-adducts, are produced v i a free carbenes. In accord w i th this conclusion, s imi lar product ratios were observed when the diha-locarbenes were generated from H C B r 3 . When 11,11-dibromo-l,6-methano[10]-annulene was used as a carbene precursor, 1 gave 57-65% of 1,4-adduct, indicat ing that now a complexed carbene was reacting (scheme 13) 6.

+ :CBr 2

KETENES

Ketenes react w i th 1,3-dienes to give 3-vinylcyclobutanones 3 ' 7 8 . Stepwise [4+2]-cycloaddi-t ion reactions across the C=0 double bond take place when donor(alkoxy or trimethylsiloxy)-substituted 1,3-dienes are combined w i th alkyl-, aryl- or haloke-tenes 7 9 , and when the electron-deficient bis(trifluo-romethyl)ketene reacts w i th buta-1,3-diene 2 0 . Only i n reactions w i th heterodienes (e.g. a,ß-unsaturated ketones and imines), the CC-double bond of diphenylketene had been reported to act as a d ienophi le 2 7 .

S C H E M E 14

Ph

c = c=o > Ph

When 1 is combined w i th diphenylketene, the [4+2]-cycloadducts 5 and 6 are produced i n a 1:1 ratio, and 6 represents the only cyclohexenone wh ich has been formed i n a Diels-Alder-reaction of a ketene 2 2 . Since cases w i th concomitant formation of vinylcyclobutanones and cyclohexenones are not known, and kinetic data for the reaction described i n scheme 14 are not available either, the difference of the activation energies of [2+2]- and [4+2]-cycloadditions for reactions of ketenes w i th ordinary 1,3-dienes cannot yet be estimated.

[4+4]-CYCLODIMERISATION OF 1

When 1 is heated at temperatures above 80 ° C , dimerisat ion takes place w i th formation of the Diels-Alder d imer 8 and the [4+4]-cyclodimer 9 2 3 . The product ratio shown i n scheme 15 reflects kinetic control since both 8 and 9 have been found to be persistent at 150 ° C . Whi le 8 may be produced by a concerted process ( ^ s + or by cyclisation of an intermediate (e.g. 7), orbital symmet iy rules 3 require a stepwise mechanism to account for the formation of 9.

376 H . Mayr, J. B a r a n a n d U. W. H e i g l

S C H E M E 15

Dimcrization of the Diene 1 in Toluene

# 150 °C

Temperature Effect on Product Ratio ( 1 bar)

T / ° C 80 100 125 150

[8]/[9] 3.4 3.7 3.9 4.2

Pressure Effect on Product Ratio (79 C )

p/bar 500 6000 9000

[8]/[9] 3.4 3.1 3.5 4.0

F r o m the product ratio determined at different temperatures (scheme 15) one can calculate AS* for the format ion of 8 to be 5 entropy units less negative than AS* for the formation of 9. Since concerted processes are usually characterised by m o r e negative activation entropies than analogous stepwise mechan isms 2 4 , this f inding is an argument for 8 being formed through an intermediate. F r om the influence of pressure on rate and product ratio, activation volumes o f -15 .8 (for 8) and -15.5 c m 3 m o H (for 9) have been determined. These values are to be compared w i th the reaction volume of -51.2 c m 3

m o H for the formation of 8. Since in ordinary Diels-Alder-reactions, the activation volumes are closely s imi lar to the reaction vo lumes 2 5 , the strong discrepancy between AV* and AV° indicates that 8 like 9 is produced by a stepwise pathway. In analogy to related studies 2 6 , the diradical 7 appears to be a reasonable intermediate.

S C H E M E 16

2-azallyl anions undergo [3"+2]-cycloadditions w i th butadiene and isoprene

R

R

2. H ,0

R= H . C H 3

N Ph „ H

Th. Kauffmann, 1971

[3~+2]-cycloadditions also w i th s-cis-fixed dienes

But:

2. H 2 0

N l T R I L E O X I D E S

Since 1,3-dipoles incorporate the 4 electron - 3 centre 7t-orbital characteristic for al ly l anions, the isolation of 12 encouraged us also to look for [4+3]-cycloadducts w i th 1,3-dipoles. Nitr i le oxides have first been selected, since their reaction w i th aryl-acetylenes has been known to yield isoxazoles and oximes concomitant ly 2 9 . The intermediate formation of diradicals or zwitterions has been inferred from this Observa t i on 3 0 3 7 .

S C H E M E 17

e e R - C E N - 0

H - C = C - Ar

N NOH

+ R - C - C = C - A r

When benzonitri le oxide, 14, was generated from benzohydroxamoyl chloride and tr imethylamine in diethyl e ther 3 7 a i n the presence of diene 1, the [3+2]-cycloadduct 15, the oxime 16, and the bisadduets 17 and 18 were produced 3 2 . Evidence for the formation of a [4+3]-cycloadduct has not been obtained. As indicated i n scheme 18, treatment of 15 w i th benzonitri le oxide, 14, affords 18 (not 17), while 17 is produced from the reaction of 16 wi th 14.

2 -AZALLYL ANIONS S C H E M E 18

The 1,3-diphenylazallylanion 10 has been reported to react w i th 1,3-butadiene and isoprene wi th exclusive formation of the 3-vinylpyrrolidine, 1 1 2 7 . Analogous reactions w i th 10 have also been observed w i th several 5-cis-fixed dienes (scheme \ 6 ) 2 8 .

W h e n the sterically hindered diene 1 was treated wi th 1,3-diphenylazallyll ithium, 10, Compound 12 was the only eyeloadduet isolated after hydrolys is 2 5 . Under certain conditions, 12 is aecompanied by the aeyclic adduet 13, suggesting a stepwise process being responsible for the formation of 12. 1 6 <7%> 1 7 <»*> (3*)

S t u d y of c y c l o a d d i t i o n m e c h a n i s m s 377

Whi le the reactions of nitri le oxides w i th aromatic rc-systems have previously been reported to yield smal l amounts of ox imes 3 3 , Compounds 16 and 17 are the first oximes that have been produced from benzonitri le oxide 14 and a non-aromatic CC double-bonded dipolarophile. The analogous reaction of 14 wi th the non-methylated bismethylenecyclopentane 4 proceeds w i th exclusive formation of the regulär 1,3-dipolar cycloaddit ion product 19 (scheme 19) 3 2 .

S C H E M E 19 Ph

If one assumes the oxime 16 to be generated by intramolecular hydrogen abstraction i n an intermediate diradical , the different behaviour of methylated and non-methylated bis(methylene)-cyclopentane (schemes 18 and 19) can be rationalised i n two ways.

S C H E M E 20

Assumpt ion : ox ime and [3+2]-cycloadduct are formed through an intermediate d i rad ica l .

l

One assumption (scheme 20) is that both products, oxime and [3+2]-cycloadducts, are produced through intermediate diradicals. If the barrier for cycl isation is considerably lower than the barrier for hydrogen transfer i n the non-methylated Compound, the exclusive formation of the cycloadduct takes place (scheme 20, left). The methyl groups i n 1 should increase the barrier for cycl isation, whi le the barr ier for hydrogen transfer should hardly be affected. Thus, the activation energies for the competing reactions become similar, and a mixture of products is formed (scheme 20, right).

Accord ing to the second assumption (scheme 21) only the oxime 16 arises from a diradical , whi le a concerted cycloaddit ion mechanism accounts for the formation of the isoxazolines. Now, the exclusive formation of a cycloadduct (scheme 21, left) wou ld be due to the fact that the activation energy for the concerted cycloaddit ion reaction is considerably lower than that for the formation of the diradical . Introduct ion of the methyl groups can now be

S C H E M E 21

Assumpt ion : ox ime is formed v i a a d i rad ica l , isoxazol ine is f o rmed by a concerted cyc loaddi t ion pathway.

expected to affect only the barrier of the cycloaddit ion, thus giving rise to the format ion of 15 and 16. Whi le methyl Substitution affects the rate-determining Step i n scheme 21, it only affects the product-determining step i n scheme 20. Therefore, kinetic experiments should al low these two possibilities to be differentiated. Compet i t ion experiments (CC1 4, 20.5 °C) showed that 1 is 26 t imes less reactive than the non-methylated Compound 4. This value implies that the cycloaddit ion of benzonitri le oxide w i th bis(methylene)cyclopentane 4 does not profit highly from concertedness. If the oxime 16 is produced through an intermediate diradical , the «energy of concert» 3 4 for the format ion of 19 must be less than 3 kcal m o H .

S C H E M E 22

Ph

23 24 25

26 (21%) 27 (4%) 28 (-10%)

378 H. Mayr, J. B a r a n and U. W. Heigl

N l T R O N E S

The reaction of C,N-diphenylnitrone, 20, w i th 1 affords several types of products, as shown in scheme 2 2 3 5 > 3 6 . F o r the formation of the spiranes 21 and 22, a concerted cycloaddit ion mechanism as wel l as a stepwise pathway wi th formation of an intermediate (e.g. 23) has to be considered. In contrast, the format ion of the [4+3]-cycloadduct 26 by a concerted process is orbital symmetry forbidden 3 . If an intermediate wi th zwitterionic character were involved, trapping wi th the solvent ethanol should be poss ib le 3 7 . Since the yields of the cycloadducts were very s imi lar i n benzene, toluene, dimethyl sulphoxide, acetonitrile and ethanol, we suggested the intermediacy of the diradical 23. This intermediate may also account for the formation of 27 and 28 since intramolecular hydrogen transfer, as discussed for the reactions of nitri le oxides, might give the hydroxylamine 24, a potential precursor of 27 and 28.

Is the formation of an intermediate diradical a special property of our model Compound 1, or is the iso lat ion of 26-28 an indicat ion that reactions of nitrones w i th 1,3-dienes generally involve diradical intermediates?

S C H E M E 23 - R E L A T I V E R A T E CONSTANTS FOR T H E REACTIONS O F C ,N -D I P H E N Y L N I T R O N E WITH 1,3-DIENES

Dipolarophile

Ph

e o ' N V H

Ph krel

(Toluene, 80° C)

AA<? /kcalmol 1

C 0 2 E t

1.0

0.033

0.13

0.42

0.0

2.4

1.4

0.6

B a r a n , M a y r , 1 9 8 9

Consider ing the smal l reactivity difference between 1 and 4 (scheme 23) and following the same l ine of arguments employed for the discussion of schemes 20 and 21, we came to the conclusion, that cycloaddit ions of diphenylnitrone 20 w i th ordinary 1,3-dienes also cannot profit highly from con-certedness, i . e . , the appearance of intermediates has to be generally considered. Therefore, a detailed analysis of the products formed from 20 and several other 1,3-dienes has been carried out.

Apart from the normal [3+2]-cycloadducts, the [4+3]-cycloadducts 29, 30 and 31 were formed i n low yields from bis(methylene)cyclopentane, 4, 2-phenyl-1,3 -butadiene, and 2,3 -dimethyl-1,3 -but a-

S C H E M E 24 - [4+3J -CYCLOADDUCTS F R O M 20 AND « N O R M A L » D IENES

29 (9%)

Ph

le F h

20 I O

51 > N " ( 30 (3%) Ph

H

Ph

(3%)

diene, respectively. Since their formation through concerted mechanisms is orbital symmetry for­bidden, the intermediacy of diradicals is again deduced. The fol lowing section shows that these intermediates are not thermally equilibrated.

When the spirane 21 is heated at 100 °C, decomposit ion w i th formation of unidenti f ied h igh molecular weight products takes place. After 60 h, more than half of the material is lost and only 6% of the [4+3]-cycloadduct 26 is observable (expt. 1, scheme 25). Under the same conditions, 22, a diastereomer of 21, selectively rearranges into 26 (expt. 2, scheme 25). Compound 26 is stable under these condit ions (expt. 3, scheme 25).

The bottom block of scheme 25 shows that the relative thermodynamic stability of [3+2]- and [3+4]-cycloadducts is reversed, when R = H instead of R = C H 3 . Now, three quarters of 21' and 22' r ema in unaffected when heated at 100 °C for 7 1 h (expts. 4 and 5, scheme 25). In contrast to 26, the non-methylated [4+3]-cycloadduct 26' rearranges into the spiranes 21' and 22' w i th high preference for the latter stereoisomer, the one wh ich is p rodu ced i n lower yield dur ing the cycloaddit ion (expt. 6, scheme 25). The greater rate of the 2 6 ^ 2 2 (and 2 6 ' ^ 22') isomerisations compared with the 26^21 (and 26 '^ 21') isomerisations clearly shows that the intermediate diradicals are not thermal ly equilibrated, i . e . , internal rotations are not fast compared w i th radical combinations.

A rational isation for the stereoselectivities of the rearrangements is given i n scheme 25. Let us assume that cleavage of the C -0 bond i n 21 and 22 is associated wi th a rotation of the planar nitroxide fragment to give the diradicals 23a and 23b, respectively, w i th an^'-alignment of the two phenyl groups. In 23b, the nitroxide oxygen is close to the CH 2 - t e rminus of the al lyl ic radical , and cycl isat ion to yield 26 v i a a boat-like transit ion State requires only smal l geometric reorganisations. The conf ormer 23a, on the other hand, has to undergo rotations around bond a or bond b before cycl isation can give 26. These rotations are obviously slow, so that side reactions are taking place and the rearrangement 21 —» 26 hardly takes place. The reverse order of arguments (principle of microscopic reversibility) can be used to explain the stereoselective rearrangement 26' —» 22'.

S t u d y of c y c l o a d d i t i o n m e c h a n i s m s 379

S C H E M E 25 - T H E R M O L Y S I S O F T H E CYCLOADDUCTS IN T O L U E N E

R2

N-Ph

R = C H 3 21 26 22

Expt l a 40 C 6 0

Expt 2 a 0 88 12 C

Expt 3 a 1 95 C 0

R = H 21' 26' 22* b

Expt 4 74 C 2 6 b

Expt 5 2 8 74°

Expt 6 b 7 20° 74

a) Composition after 60 h at 100° C; b) Composition after 71 h at 100° C; c) Starting material (=100 at t=0).

C O N C L U S I O N

Several new types of cycloadditions have been realised by using the sterically hindered 1,3-diene as a cycloaddit ion partner. Complementing Huisgen's work on stepwise 1,3-dipolar cycloadditions v i a zwitterionic intermediates (scheme 2 6 ) 3 8 , we have found that 1,3-dipolar cycloadditions may also occur stepwise, i f the termini of the potential intermediate carry radical-stabil ising groups.

S C H E M E 26

can influence rate and/or p r o d u c t s of the reaction (a-d, scheme 27).

S C H E M E 27

Compare the reactivity of 4 and 1:

Methylation affects rate

Methylation affects products

Conclusion

a no no None b no yes Stepwise mechanism with 4 and 1 c yes no Concerted mechanism with 4 and 1 d yes yes Concerted mechanism with 4, stepwise

mechanism with 1

Ion stabilising groups at the intermediate's termini

R 2 C*

H j C C ^ C - c '

CH 2

' C N

NC

H u i s g e n , M i o s t o n , L a n g h a l s

Radical stabilising groups at the intermediate's termini

Ph Ph

. N . •o

C r C

R 2C

T h i s work

CASE a

If Compounds 4 and 1 exclusively give 1,2-adducts w i th s imi lar rates, this may be due to a stepwise mechanism or to a concerted mechanism w i th an early transition State, wh ich does not experience an extra steric strain by the methyl groups. N o mechanistic conclusion can be drawn f rom the comparison of 4 and 1.

In wh ich cases can Compound 1 be used as a mechanistic probe? Scheme 11 has shown that 1 shows a normal „ 4 g reactivity, i . e . , this Compound wi l l not exhibit special effects for reactions, wh i ch normal ly take place in 1- a n d 4 -pos i t i on of a 1,3-diene. Let us, therefore, consider cycloadditions, for wh i ch the simultaneous attack to positions 1 and 4 is orbi ta l symmetry forbidden, and wh ich usually employ a n 2-uni t of a 1,3-diene. When we now compare the reactivity of 1 and 4, the methyl groups

CASE b

If Compounds 4 and 1 give different products w i th s imi lar rates, one can conclude that the methyl groups only affect the product-determining step, not the rate-determining step. This w i l l be the case i f both dienes reacted through an intermediate (scheme 28). However, the Observation of different products formed w i th s imi lar rates is also compatible w i t h a concerted cycloaddit ion of 4 when the energy of

380 H . M a y r , J. B a r a n a n d U. W. H e i g l

S C H E M E 28 - E N E R G Y P R O F I L E S FOR T H E R E A C T I O N S O F 4 ( L E F T ) A N D 1 (R IGHT) WITH CYCLOADDIT ION P A R T N E R S THAT U S U A L L Y P R E F E R 1,2-ATTACK

Case b

Case c

Case d

concert is very smal l , i . e . , when the barriers for the concerted and the stepwise processes are of s imi lar height.

CASES C AND d

When methylation strongly reduces the rate, a concerted reaction of 4 is indicated, since the steric effect of the methyl groups can only be realised, when C-2 is attacked i n the rate-determining step. If the energy of concert is very large, the methyl groups are unable to change the mechanism (case c, schemes 27 and 28). If the steric strain caused by the methyl groups exceeds the «energy of concert», a change of mechanism takes place, indicated by the Observation that 1 gives addit ional or different products than 4 (case d, schemes 27 and 28). In this case, A A G * gives a rough estimate for the energy of concert, that is encountered i n the reaction w i th a «normal diene» (fi.g. 4).

As the effect of methyl groups on the attack at the diene-termini is not exactly zero (see scheme 11),

many Systems w i l l not provide a clear yes/no answer. We believe, however, that a large r e a c t i v i t y difference b e t w e e n 1 and 4 is a r e l i a b l e i n d i c a t i o n t h a t a c o n c e r t e d m e c h a n i s m is o p e r a t i n g w i t h o r d i n a r y d i e n e s .

It may seem, as i f any cycloaddend w i th bulky substituents at one end (e.g. tert-butyl-substituted ethylenes) could serve as an analogous mechanist ic probe. This is not the case, however, since ordinar i ly a strong reduction of rate caused by a bulky substituent may either indicate the increase of the barrier of the concerted process or signify that the cycl isation of a reversibly produced intermediate is slowed down by steric effects. The latter possibi l i ty can be excluded i n reactions wi th Compound 1: In a potential intermediate, there is always one non-shielded al lyl ic posit ion (the terminal CH 2 -group) , wh i ch can be attacked i n the cycl isat ion step. Since concerted 1,2-additions are also discussed i n several hydrogenation and oxidation reactions, further areas of appl icat ion for 1 are conceivable. The convenient access described i n scheme 7 encourages further experiments.

We thank W. Hellebrandt for experimental assistance and the Deutsche Forschungsge­meinschaft and the Fonds der Chemischen Industrie for f inancial support.

R e c e i v e d F e b r u a r y l l t h 1 9 9 1

R E F E R E N C E S

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