18 Heterocyclic Chemistry Part (i) Saturated Ring Systems” By I. D. BLACKBURNE and M. J. COOK School of Chemical Sciences University of East Anglia Norwich NOR 88C 1 Three-membered Rings The first report of nitrene intermediates in the photolysis of aziridines e.g. (l) promises to provide a useful route to other aziridines by the trapping of thenitrene with appropriate olefins.’ Whereas an example of the 1-azabicyclo[ l,l,O]butane system is known the 2-aza-isomer has yet to be isolated although evidence for its existence as an intermediate (2) has been reported;2 cf the intermediacy of 2-oxabicyclo[l,l,O]butane (3).3 The new 2,4-diazabicyclo[l,l,O]butane(4) ob-tained by condensation of formaldehyde with a primary amine and an aminating agent and the new 5-azabicyclo[2,1 ,O]pentane (5)2 have been prepared and both are relatively stable; in particular the latter unlike the highly strained carbocyclic analogue shows no tendency to react with acetylene dicarboxylate.The quantitative preparation of the oxaspiropentane (6) and its lithium iodide- T. L. Gilchrist C. W. Rees and E. Stanton J. Chem. SOC.(0,1971. 988. ’ J. N. Labows jun. and D. Swern Tetrahedron Letters 1971 4523. L. E. Friedrich and R. A. Cormier Tetrahedron Letters 1971 4761. A. A. Dudinskaya L. I. Khmelnitski I. D. Petrova E. B. Baryshnikova and S. S. Novikov Tetrahedron 1971 27 4053. * Including simple unsaturated compounds which are not ‘aromatic’ ‘antiaromatic’ etc. 551 I. D. Blackburne and M. J. Cook Me HN’JNR ~N.CO,E~ 0 U (4) Me (5) catalysed rearrangement have also been rep~rted,~ the rearrangement providing a rapid high-yield route to cyclobutanone.Studies on aziridine and oxiran ring-opening by carbon-carbon bond cleavage have continued. In the nitrogen series kinetic experiments show that rates of cycloaddition to active dipolarophiles are determined only by the first-order ring scission to the azomethine ylides.6 Azomethine ylides have been found to be amongst the few 1,3-dipoles that equal ozone in their ability to attack an aromatic double bond. Thus (7) has been shown to undergo cycloaddition with phenanthrene,’ and it also provides the first example of 1,3-dipolar addition to azobenzene forming the triazolidine (8).8 Previously azobenzene had only been observed to undergo [2+ 2]cycloadditions with keten.In the oxiran system thermal ring-opening to the carbonyl ylide [(9a) (9b)l has now been demonstrated to proceed by way of the expected conrotatory proce~s,~ cf Ar Ar J. R. Salaiin and J. M. Conia. Chem. Comm.. 1971 1579. R. Huisgen and H. Mader J. Amer. Chem. SOC.,1971 93 1777; H. Hermann R. Huisgen and H. Mader ibid. p. 1779. ’ R. Huisgen and W. Scheer Tetrahedron Letters 1971 481. E. Brunn and R. Huisgen Tetrahedron Letters 1971 473. A. Dahmen H. Hamberger R. Huisgen and V. Markowski Chem. Comm. 197 1,1192. Heterocyclic Chemistry-Part (i) Saturated Ring Systems aziridines and cyclopropyl anions. Carbonyl ylides have been trapped by acety- lenes," olefins," and carbonyl compounds' to give dihydrofurans tetra-hydrofurans and dioxolans respectively.N-Inversion in aziridines continues to be a field which attracts attention. The well-recognized slow inversion may in fact be hastened by introduction of a halogen at a ring carbon e.g. (10); the enhanced rate can be explained in terms of 'double-bond-no bond' resonance in which contributions from planar forms (lob) facilitate the inversion. l2 On the topic of positively charged three-membered rings the preparation for the first time of a solution of the unstable aziridine N-oxide system (11) by ozonolysis of the corresponding aziridines is particularly noteworthy. The decompositions of the N-oxides (12 13; X = NR)13 and of the analogous episulphoxides (12 13; X = S)I4 have been elucidated and shown to follow two distinct pathways the less facile but partially stereospecific path B is pre-ferred when the stereochemistry is unfavourable for the hydrogen-transfer reaction A.The peroxy-epoxide (14) has been suggested as a key intermediate in a unifying concept of the mechanism of ozonolysis of 01efins.l~ OHI -0 Bu' \/ R'AR2 X+ 0-I R 0-0'Io+ AR2R' 5 WR+x=o (14) LO H. Hamberger and R. Huisgen Chem. Comm. 1971 1190. A. Robert J.-J. Pommeret and A. Foucaud Tetrahedron Letters 1971 231. D. J. Anderson and T. L. Gilchrist J. Chem. SOC.(C) 1971,2273. l3 J. E. Baldwin A. K. Bhatnagar Se Chun Choi and T. J. Shortridge J. Amer. Chem. SOC.,1971 93 4082. l4 J. E. Baldwin G. Hofle. and Se Chun Choi J. Amer. Chem. SOC.1971 93 2810; K. Kondo and A. Negishi Tetrahedron 1971 27 4821. P. R. Story J. A. Alford W. C. Ray and J. R. Burgess J. Amer. Chem. SOC.,1971 93 3044. 554 I. D. Blackburne and M. J. Cook The reaction of 1-azirines (15) with hydrazine to give tetrahydro- 1,2,4-triazin- 6-ones was reported last year16 but the product is now known to be accompanied by small yields of 2-hydrazinoaziridines (16; Y = NH,).” The products of the reaction provide a sharp contrast to those of the corresponding reaction with hydroxylamine where 2-hydroxyaminoaziridine (16; Y = OH) is formed in nearly quantitative yield.’* H RNH R I \ 40 I C CONH H-C-Br I ArAAr -.A0 CONH I bisnorcholany 1 bisnorcholanyl (15) (16) (17) (18) The first preparation of optically pure a-lactams (18) of known configuration has been ~1aimed.l~ The compounds are obtained fiom the optically active a-halogenoamides (17) which cyclize with inversion of configuration.The exis- tence of a-lactones (19) evidence for which was reported last year,” has been further substantiated by the trapping of the dipolar form with methanol to give a-methoxy-acids (20).’ The precursor of the a-lactone provides an alternative to that reported previously. Oxaziridines appear to be the most widely studied three-membered rings containing two heteroatoms. A high-yield preparation involving the molyb- denum(v)-catalysed oxidation of Schiff bases with t-amylhydroperoxide has been reported and the authors suggest” that this is more convenient than the peracid procedure.A detailed examination of the oxaziridine-nitrone equili- brium (21) an analogue of the aziridine-azomethine ylide system (see above) has been ~ndertaken,~~ and it has been shown that the photocyclization of (21b) 16 Ann. Reports (B) 1970 67 434. 17 T. Nishiwaki and T. Saito J. Chem. SOC.(0,1971,2648. 18 T. Nishiwaki and S. Onomura J. Chem. SOC.(C),1971 3026. 19 S. Sarel B. A. Weissman and Y. Stein Tetrahedron Letters 1971 373. 20 Ann. Reports (B) 1970 67 436. 21 W. Adam and R. Rucktaschel J. Amer. Chem. SOC.,1971.93 557. 22 G. A. Tolstikov U. M. Jemilev V. P. Jurjev F. B. Gurshanov and S. R. Rafikov. Tetrahedron Letters 197 1 2807. 13 J. S. Splitter Tah-Mun Su H. Ono and M. Calvin J. Amer. Chem. SOC.,1971 93 407 5.Heterocyclic Chemistry-Part (i)Saturated Ring Systems 555 is stereospecific in accordance with orbital-symmetry rules. The corresponding thermal cleavage of (21a) gives a 50:50 mixture of cis-and trans-(2lb) the iso- meric products resulting from the two possible conrotatory motions of carbon- oxygen cleavage. Reaction of oxaziridines with thiourea deoxygenates the ring to a Schiff base perhaps by way of the unknown thiaziridine intermediate (22) which is postulated to eliminate sulphur spontane~usly.~~ A further paper on the oxaziridine system provides an unusual example of reversal of heteroatom basicity. Data for a series of 2-t-butyloxaziridines are suggestive of O-protona-tion :a reflection amongst other things of steric congestion about the nitrogen atom.25 0 2 Four-membered Rings Various syntheses of four-membered ring compounds containing one heteroatom have been published.These include an improved route to 3-azetidin0ls,~~ the photosensitized preparation of the polycyclic azetidine (23),2' the first prepara- tion of the parent 2-methylene-oxetan (24),28and the synthesis of the hitherto unknown 2-alkyl-(or aryl-) l-a~etines.~' A precautionary note on the synthesis of 3-thietanol-1,l-dioxide has appeared and a less hazardous procedure is ~uggested.~' Asymmetric induction has been observed in the [2 +2lcycloaddition of sulphene to optically active enamines and this appears to be the first applica- tion of asymmetric synthesis to four-membered rings.31 The thietan 1,l-dioxide (25) was produced in 6% optical purity whereas (26) which has the reverse /vMe H Me 24 D.St. C. Black and K. G. Watson Angew. Chem. Internat. Edn. 1971 10 327. 25 A. R. Butler and B. C. Challis J. Chem. SOC.(B) 1971 778. 26 E. H. Gold J. Amer. Chem. SOC.,1971,93 2793. 27 P. D. Rosso J. Oberdier and J. S. Swenton Tetrahedron Letters 1971 3947. 28 P. F. Hudrlik and A. M. Hudrlik Tetrahedron Letters 1971 1361. 29 A. B. Levy and A. Hassner J. Amer. Chem. SOC.,1971,93,2051. 30 D. C. Dittmer M. E. Christy N. Takashina R.S. Henion and J. M. Balquist J. Org. Chem. 1971,36 1324. 31 L. A. Paquette J. P. Freeman and S. Maiorana Tetrahedron 1971 27 2599. I. D.Blackburne and M. J. Cook stereochemistry was obtained in 25 % optical purity ;stereospecificity evidently increases as the number of rotational degrees of freedom is reduced.A number of rearrangements of four-membered rings have been reported. In the sulphur series,32 the cis- and trans-sulphones (27) ring-expand to the corresponding sulphinic esters (28) on treatment with t-butoxymagnesium bromide32" [cf the thermally induced isomerization (29) +(30) reported two years ago33] but in sharp contrast both isomers give the trans-diphenylcyclo- propyl derivative (31) on treatment with ethylmagnesium bromide.32b As a further contrast the cis- and trans-sulphoxides (32) both give cis-diphenyl- cyclopropyl derivatives with t-butoxide in DMF the anion (33) subsequently undergoing disprop~rtionation.~~' Reaction of trans-diphenylthietan (34) with t-butoxide probably also proceeds via a diphenylcyclopropyl derivative (39 but this was not isolated.32b Apart from the oxidation state of the sulphur atom and the strength of the base proton availability is also a parameter determining the reaction pathway in this series :it is notable that in a protic medium (methano- lic methoxide) the trans-sulphone (27) and the trans-sulphoxide (32) are merely epimerized to their cis-isomers and do not rearrange.Ph + rh+€'h 1 -PhqPh + PhqPh so Ph so- SH SO H (32) (33) A new synthesis of /I-lactams by ring expansion of cyclopropanone derivatives seemingly provides a basis for a more general route than some already realized (Scheme l).34 The photochemical conversion of some diazomalonic ester 32 (a) R.M. Dodson P. D. Hammen and R.A. Davis J. Org. Chem. 1971 36 2693; (b)R. M. Dodson P. D. Hammen E. H. Jancis and G.Klose ibid. p. 2698; (c)R. M. Dodson P. D. Hammen and J. Yu Fan ibid. p. 2703; R. M. Dodson and J. Yu Fan ibid. p. 2708. 33 Ann. Reports (B) 1969 66 431. 34 H. H. Wasserman H. W. Adickes and 0.Espejo de Ochoa J. Amer. Chem. Soc. 1971 93 5586. Heterocyclic Chemistry-Part (i) Saturated Ring Systems 557 amides into lactams e.g. (36) into (37) has now been found to give the cis- as well as the normal trans-product and offers a direct route to the nucleus of the penicillin and cephalosporin antibiotic^.^^ A further approach to new types of p-lactam antibiotics is now feasible through the isolation of the P-lactam function Scheme 1 But0,C-YN2 ‘s\l C-N 0 O4 C0,CH Ph C02CH2Ph Buto2caL (36) (37) of penicillins.36 The process involves cleavage of the S-1-C-2 bond by pyrolysis of the penicillin sulphoxide followed by treatment with diazomethane and then zinc in acetic acid (Scheme 2). R’ -Zn-HOAc -J-NH ol$;2R2 0 N Scheme 2 An unexpected difference has been observed between iodolactonization a traditional method of obtaining y-lactones from &unsaturated acids and bromolactonization which now has been shown to favour P-lactone formation. 35 G. Lowe and J. Parker Chem. Comm. 1971 577. 36 (a)D. H. R. Barton D. G. T. Greig P. G. Sammes and M. V. Taylor Chem. Comm. 1971,845 ;(b)D. H. R. Barton P. G. Sammes M. V. Taylor C.M. Cooper G. Hewitt B. E. Looker and W. G. E. Underwood ibid. p. 1137. 558 I. D. Blackburne and M. J. Cook Thus treatment of the conformationally rigid (38) with one equivalent of bromine yielded (39):37a and more remarkably open-chain acids (40) also form P-lactones (41) even when R' = R2 = H where isomerization to the up-unsaturated acid is possible.37b Me Me CO H R2 Routes to four-membered rings containing two heteroatoms include a new enamine reaction which has been reported to provide a possible general pathway to 1,2-diazetidines thus cyclohexanone enamines e.g. (42) react with diben-zoyldi-imide at room temperature to give structures of type (43) in nearly quanti- tative yield.38 Isolation of 1,2-dioxetan compounds e.g. (44),from the photo-oxidation of ole fin^,^^ and their chemiluminescence in the presence of a fluorescent hydro- carbon during thermal decomposition continues to attract interest.Activation energies for the overall luminescent process and for dioxetan cleavage of (44) are the same (24 kcal mol- ') and there is no alternative low activation energy dark pathway for decomp~sition.~~~ Thermal decomposition of trimethyl- dioxetan in the presence of lanthanide chelates has been observed to produce narrow-band chemiluminescence of moderate efficiency the wavelength of which is dependent upon the metal complex. Such systems might reasonably be used as chemical sources of 'monochromatic' light of chosen wavelength and be devised to generate a specific number of photons.40 The 1,3-dithietan ring (45) has been obtained by the first reported photocyclo- addition reactions of an alicyclic thioketone adamantanethi~ne.~' The reactive N-COPh Et0)r8 NCOPh EtO (44) 0 37 (a) W.E. Barnett and J. C. McKenna Chem. Comm. 1971 551; (b) W. E. Barnett and J. C. McKenna Tetrahedron Letters 1971 2595. 38 L. Marchetti and G.Tosi Tetrahedron Letters 1971 3071. 39 (a) A. P. Schaap Tetrahedron Letters 1971 1757; (b) T. Wilson and A. P. Schaap J. Amer. Chem. SOC.,1971 93 4126. 40 P. D. Wildes and E. H. White J. Amer. Chem. SOC.,1971 93 6286. 41 C. C. Liao and P. de Mayo Chem. Comm. 1971 1525. Heterocyclic Chemistry-Part (i) Saturated Ring Systems species is a triplet which apart from dimerizing may react to give alkene addition products (46).Other reports on the preparation of dithietan derivatives have appeared which demonstrate the versatility of carbon disulphide in synthesis.42 3 Five-memberedRings A method of heterocyclic synthesis by cyclization of olefinic amines in the presence of a mercuric salt has been reported.43 The products mercurated nitrogen heterocycles generated by trans-addition to the olefin may be demercurated by sodium borohydride. Thus (47) yields solely (48),and (49) yields both five- and six-membered ring products (50) and (5l) the relative proportions depending on the solvent and the mercury salt employed. Other cyclizations of N-substituted -N -N, INHP~ \ Pr Pr (47) (48) Me Me Me I I I m+W'gy \ \ (49) olefinic amines e.g.(52; X = NO)44"and (52; X = Cl),44b proceed via free- radical mechanisms and lead to five-membered nitrogen rings only providing convenient routes to derivatives of lesser known isomers of tropane e.g.(53)-(55) ; (54)has also been prepared by a fluoroacetic acid-catalysed cyclization of (56).45 Comparable intramolecular radical additions of olefinic thiols (57)have led to 42 Y. Hayashi T. Akazawa K. Yamamoto and R. Oda Tetrahedron Letters 1971 1781 ; P. Yates D. R. Moore and T. R. Lynch Canad. J. Chern. 1971,49 1456. 43 J. Perie J. P. Laval and A. Lattes Compt. rend. 1971 272 C 1141; J. Perie J. P. Laval J. Roussel and A. Lattes Tetrahedron Letters 1971 4399. 44 (a)Y. L. Chow R. A. Perry B. C. Menon and S. C. Chen Tetrahedron Letters.1971 1545; Y. L. Chow R. A. Perry and B. C. Menon ibid. p. 1549; (6) J.-M. Surzur L. Stella and R. Nouguier ibid. p. 903. 4s G. Esposito R. Furstoss and B. Waegell Tetrahedron Letters 1971 899. I. D. Blackburne and M. J. Cook the first syntheses of two thiabicyclo-octane systems (58)and (59),but in contrast with the amino-olefin cyclization formation of the [2,2,2]bicyclo system seems to be favoured over formation of the [3,2,1] system.46 Thus when R = H (58) is the sole product some (59) being formed along with (58) when R = Me. The Ramberg-Backlund reaction of a-halogenosulphones continues to provide synthetic routes to interesting compounds such as the strained pro- pellane (60):’ and the products (61) and (62) of a novel ‘bishomoconjugative Ramberg-Backlund rearrangement’.48 Chlorination of sulphones with sulphuryl chloride somewhat unexpectedly gives the P-chlorinated product in contrast with sulphides and sulphoxides which undergo a-~hlorination.~~ 46 J.-M.Surzur R. Nouguier M.-P. Crozet and C. Dupuy Tetrahedron Letters 1971 2035. ” L. A. Paquette and R. W. Homer J. Amer. Chem. SOC.,1971,93,4522. 48 L. A. Paquette R. E. Wingard jun. and R. H. Meisinger J. Amer. Chem. SOC.,1971 93 1047. 49 I. Tabushi Y. Tamaru and Z. Yoshida Tetrahedron Letters 1971 3893. Heterocyclic Chemistry-Part (i) Saturated Ring Systems C1 Alkylphosphonium salts normally react with base by loss of an a-proton but reaction of the small-ring salt (63) with methyl-lithium results in attack at phosphorus.This pathway relieves ring strain and yields the first stable penta- alkylphosphorane (64).50 The first resolution of a chiral cyclic phosphorus compound (65) is claimed the laevorotatory form being obtained via the (+)-9-camphorsulphonate salt.51 The recently synthesized methyleneaminophos- phanes which are novel 1,3-dipoles having high nucleophilic ~haracter,~ 2a have been shown to react with electrophilic olefins to produce compounds of type (66).52b The synthesis of the 4,5-dihydro-3-azaphosphole(67) by reaction of phenylphosphine with vinyl isocyanide has also been reported.53 Me NEt X2P-N=CPhz \ + CpP CH2=CHR x‘/\ x Some novel cleavage reactions of rings containing heteroatoms in the 1-and 3-positions should find applications in synthesis.Trityl fluoroborate cleaves 1,3-dioxolans to form a-ketols e.g. (68) 4(69),54 and ozonolysis affords esters in essentially quantitative yields e.g. (70) +(71).55 The latter reaction is general 50 E. W. Turnblom and T. J. Katz J. Amer. Chem. SOC.,1971 93,4065. s1 G.Ostrogovich and F. Kerek Angew. Chem. Internat. Edn. 1971 10 498. 52 (a)A. Schmidpeter and W. Zeiss Chem. Ber. 1971 104 1199; (6) A. Schmidpeter and W. Zeiss Angew. Chem. Znternat. Edn. 1971 10 396. ’’ R. B. King and A. Efraty J. Amer. Chem. SOC.,1971 93,564. 54 D.H. R. Barton P. D. Magnus G. Smith and D. Zurr Chem. Comm. 1971 861. 55 P. Deslongchamps and C. Moreau Canad. J. Chem. 1971 49,2465. 562 I. D. Blackburne and M. J. Cook for a range of acetals and ketals and an interesting specificity is suggested by the into conversion of methy1-2,3,4,6-tetra-0-acetyl-~-~-glucopyranoside2,3,4,6-tetra-0-acetylgluconate whilst the a-anomer remains unreacted.Milder con- ditions are now available for the generation of aldehydes and ketones from the 1,3-dithiolan ring. Basic hydrolysis of the bis-sulphoxide derivative rather than the bis-sulphone is now re~ommended,~~ and still a further improvement may lie in the use of sodium N-chlorotoluene-p-sulphonamide(Chloramine T) which rapidly and efficiently cleaves both 1,3-dithiolans’ and 1,3-oxathio- lans’ 7b directly at room temperature. Mercury(@ successfully catalyses the thiazolidine hydrolysis (72) -P (73) a key step in a scheme for aldehyde synthe- sis,” and nitrogen dioxide has proved appropriate for a novel convenient and highly efficient regeneration of ketones from doxy1 derivatives e.g.(74),59 an important class of biological spin labels. Ph 011 Ph -+ \ CH-C-Ph C6H,b3-(I) -+ C,H,,CO,CH,CH,OH Ph /Ph II 0 (71) (68) (69) (70) (72) (74) The assumption that thioketones react with amines to form Schiff bases should be treated with some caution. Thiobenzophenone has been shown to react with a number of primary amines as well as with diethylamine to yield the thermally labile thio-ozonide (75).60 Structures of the 1,2,4-trithiolan type (76) and (77) have also been assigned to the products of the oxidation of both fl-ketodithioic (75) (76) Y = RCOCH (77) Y = PhNH-N (78) 56 P.R. Heaton J. M. Midgley and W. B. Whalley Chem. Comm. 1971 750. ’’ W. J. F. Huurdeman H. Wynberg and D. W. Emerson Tetrahedron Letters 1971 3449; D. W. Emerson and H. Wynberg ibid. p 3445. L. J. Altman and S. L. Richheimer Tetrahedron Letters 1971. 4709. 59 J. A. Nelson S. Chou and T. A. Spencer Chem. Comm. 1971 1580. 6o M. M. Campbell and D. M. Evgenios Chem. Comm. 1971 179. Heterocyclic Chemistry-Part (i) Saturated Ring Systems 563 acids6' and phenyldithiocarbazic acid.62 Spectral data for (76) indicate strong conjugative interactions between the sulphur atoms and the carbonyl groups. Five-membered cyclic phosphites have been shown to exhibit greatly reduced nucleophilic reactivity compared to their acyclic analogues ; this is attributed to the increased ring strain accompanying quaternization at pho~phorus.~~ This ring strain factor can suppress the normally exothermic Arbusov-type reaction of phosphor amid ate^.^^ Contrary to assertions that phosphorus inversion in phosphochloridites is rapid configurational stability is demon- strated by (78) and it is suggested that the tendency towards inversion depends solely on sample purity.65 4 Six-memberedRings In a comprehensive study experimental evidence has been presented which clearly establishes the previously disputed equatorial quaternization of nitrogen throughout the tropane series.66 On the synthesis side a large section of a diamond-type lattice (SO) has been prepared uia treatment of (79) with ethyl a-brom~methylacrylate,~~ intramole-cular quaternization has yielded the novel heterocycle (S1),68 aluminium chloride- catalysed cyclization of substituted allylthioglycollic acid chlorides (82) to dihydrothiapyran-3-ones provided a route uia (83) to the hitherto unknown parent (84),69and a novel cyclization of ad-dibromoadipic acid dianilide for Et x-0 N Et0,C aN3 (79) X = Br C104,or picrate Et0,C P (81) (84) " P.YatesandT. R. Lynch Canad. J. Chem. 1971,49 1477. '* G. Casalone and A. Mugnoli J. Chem. Soc. (B) 1971,415. b3 C. Brown R. F. Hudson V. T. Rice and A. R. Thompson Chem. Comm. 1971 1255. 64 C. Brown and R. F. Hudson Tetrahedron Letters 1971 3191. 65 R. H. Cox M. G. Newton and B. S. Campbell J. Amer. Chem. SOC.,1971 93 528. " G. Fodor R.V. Chastain jun. D. Frehel M. J. Cooper N. Mandava and E. L. Gooden J. Amer. Chem. SOC.,1971 93 403. " H. Stetter and K. Komorowski Chem. Ber. 1971 104 75. " C. H. Chen and K. D. Berlin J. Urg. Chem. 1971,36 2791. '9 K. Sato S. Inoue and K. Kondo J. Org. Chem. 1971 36 2077. 564 I. D. Blackburne and M. J. Cook which potassium fluoride was the only successful catalyst encountered has given the bicyclic lactam (SS).” Allylic ammonium ylides normally undergo rapid sigmatropic rearrangement e.g. (86)+(87). However as expected such rearrangements are notably slowed or inhibited by unfavourable transition state geometry and this is exemplified by the alternative generation of the carbonyl-stabilized ylide (89) from (SS).” 0 0 Yh Br-/ I CHzCH=CHPh CH,CH=CHPh (88) (89) The dihydropyridine formed on condensing aniline with butanal was earlier assigned structure (90) its reaction with a dienophile being presumed to result from a concerted 1,3-hydrogen shift during cycloaddition.However this process [n2s+.2 +02s +.2,] is now recognized to be thermally forbidden and a re-investigation has revealed that the dihydropyridine possesses structure (91).72 The conclusion is reached that there is no authentic concerted diene reaction of 1,4-dihydropyridines. This is in accord with the reaction of 1.4-dihydropyridines with acetylene dicarboxylate which gives fused cyclobutene derivative^,^^" and the further observation that with acrylonitrile adducts of type (92) are formed,73b unless the 4-position is fully substituted when the ring is inert to this reagent.R’ (90) (91) (92) 70 I. Shahak S. Rozen and E. D. Bergmann J. Org. Chem. 1971 36 501. 71 S. Mageswaran W. D. Ollis I. 0. Sutherland and Y. Thebtaranonth Chem. Comm. 1971 1494. 12 G. Krow E. Michener and K. C. Ramey Tetrahedron Letters 1971 3653. 73 (a) R. M. Acheson and N. D. Wright Chem. Comm. 1971 1421; (b) R. A. Sulzbach and A. F. M. Iqbal Angew. Chem. Internat. Edn. 1971 733. Heterocyclic Chemistry-Part (i) Saturated Ring Systems 56 5 7°2Me C0,Me Pr Me (93) (94) (95) Other groups report that a 2,3-dihydropyridine (93) is formed from butanal and ammonium acetate in acetic acid,74 and that the thermal ring expansion of the 1,2-dihydropyridine (94) gives the 3H-azepine (95).75 The decomposition of cyclic diaza-alkanes continues to be a field of active interest.76 Variations reported this year include the Lewis-acid-catalysed re- organization of the N-oxide (96; Y = Nf-O-) to benzaldehyde ~xime~~ and the pyrolysis of diazabasketene itself (96; Y = N) to azocine (97) rather than to ~ubane.~' Both rearrangements proceed with loss of HCN and the inter- mediacy of structures (98 Y = N+-O-BF,) and (98 Y = N) is suggested.The high preference shown by lithium for the equatorial position in 6-lithio- sultones and 2-lithiodithia1-1~~~ provides a route for stereospecific equatorial alkylations or deuteriation of these rings. Furthermore treatment of (99 ; R = Me or Ph) with butyl-lithium followed by quenching affords the isomer (99) Li 1 R R (100) 74 H.B. Charman and J. M. Rowe Chem. Comm. 1971,476. 75 T. J. van Bergen and R. M. Kellogg J. Org. Chem. 1971,36 978. 76 Ann. Reports (B) 1970 67 448; K. Shen. J. Amer. Chem. SOC.,1971 93 3064; D. E. McGreer and J. W. McKinley Canad. J. Chem. 1971 49 105; B. M. Trost and R. M. Cory J. Amer. Chem. SOC.,1971,93 5572 5573. 77 J. P. Snyder L. Lee and D. G. Farnum J. Amer. Chem. SOC.,1971,93 3816. 78 D. W. McNeil M. E. Kent E. Hedaya P. F. D'Angelo and P. 0. Schissel J. Amer. Chem. SOC.,1971,93 3817. 79 (a) T. Durst Tetrahedron Letters 1971 4171; (b) A. A. Hartmann and E. L. Eliel J. Amer. Chem. SOC.,1971 93 2572. 5 66 I. D.Biackburne and M. J. Cook Scheme 3 ( A new heterolytic fragmentation involving the anion of 1,3-dithianyl tosylates (Scheme 3)” may have synthetic applications as may Scheme 4 which provides a means of aldehyde homologation.8 Scheme 4 Some unusual cycloadditions have been reported which include the reaction of the keten-SO adduct with (101) to yield (102),” and the capture of very weakly dipolarophilic alkyl ketones by the intermediate 174-dipole (104) resulting from the spontaneous reaction of (103) with vinyl ethers.83 An unequivocal example of a [3+ l]cycloaddition has also been described in which the 1,3- dipolar azomethine imine derived from dissociation of (105)is trapped by t-butyl isocyanide to give (106).84 Ph Ph Ph >c=N-c,H,M~-~ + C H,Me-p Ph OR I CH H,C’+ \ I Ph (104) *O J.A. Marshall and J. L. Belletire Tetrahedron Letters 1971 871. F. A. Carey and J. R. Neergaard J. Org. Chem. 1971,36 273 1. 82 J. M. Bohen and M. M. Joullie Tetrahedron Letters 1971 1815. 83 S. R. Turner L. J. Guilbault and G. B. Butler J. Org. Chem. 1971 36 2838. 84 J. A. Deyrup Tetrahedron Letters 1971 2191. Heterocyclic Chemistry-Part (i) Saturated Ring Systems Conformational Analysis.-A substantial number of papers have appeared on conformational studies of various six-membered ring compounds. Further applications of the ultrasonic relaxation method' have provided data for more- stable to less-stable chair-chair inversion barriers in 2-methoxy-l ,3-dioxanss5" and more importantly data for the twist-boat to chair (tk)inversions in some alkylated 1,3-dio~ans.~'~ Together with results for chair<hair (c-c) inversion barriers the latter results allow energy parameters for the tb Sc equilibrium to be obtained directly by experiment.Variable-temperature n.m.r. has been applied to an ever-widening range of ring compounds and an unusually low c-c barrier (AGI = 5.5 kcal mol-') has been reported for the silane (107) which is attributed to the long C-Si bonds.'6 In the low-temperature spectrum of the tetrathian (108) all three rate processes ec,c-tb and pseudorotation (twist-twist) have been observed and a lower limit of 10 kcal mol- ' is assigned to the twist-twist process" (cf 0.8 kcal mol-' in cyclohexane). /\ I Me Me F The 19F n.m.r.spectrum of the N-fluoropiperidine (109)shows that N-inversion is slow on the n.m.r. time-scale up to 60"C and the authors report a ratio of axial lone-pair to equatorial lone-pair of 95 5." 'H N.m.r. and 13C n.m.r. studies suggest that the lone pair in piperidine itself is preferentially equatorial when complexed with a shift reagent.'9 R5 ((I) G. Eccleston E. Wyn-Jones and W. J. Orville-Thomas J. Chem. Soc. (B) 1971. 1551 ; (b)G. Eccleston and E. Wyn-Jones ibid. p. 2469. 86 C. H. Bushweller J. W. O'Neil and H. S. Bilofsky Tetrahedron 1971 27 3065. " C. H. Bushweller G. U. Rao and F. H. Bissett J. Amer. Chem. Soc. 1971 93 3058. J. Cantacuzene and J. Leroy J. Amer. Chem. SOC.,1971 93 5263. 89 I. Morishima K. Okada T. Yonezawa and K. Goto J.Amer. Chem. SOC.,1971 93 3922; I. Morishima K. Okada M. Ohashi and T. Yonezawa Chem. Comm. 1971 33. 568 I. D.Bluckburne and M. J. Cook Tetrahydro-1,3-oxazines and hexahydro-1,3-diazines continue to attract study.” J(NHCH) couplings have been observedgoa in both systems and indicate that N-H protons are predominantly if not exclusively axial a result which is discussed in terms of the generalized anomeric effect cf the ‘rabbit ear effect’. N-Alkyl substituents on rings lacking a substituent at C-2 are preferen- tially equatorial and it has been suggestedgob that the ‘rabbit ear effect’ may be rather less important than was at one time thought. Presumably however dipolar effects contribute substantially to the factors which lead to the observed axial preference of the N-But group in (1 But I 0 s+ I & 0 0 The proton hyperfine splitting constants in the nitroxyl radical (1 11) have been used to show that the N-0 group is predominantly The N-oxide bond of N-methylmorpholine N-oxide also shows an axial preferen~e,~~ as do the semipolar S-0 bonds in (1 12 X = 0 or S),94 cJ sulphoxides and sulphites.Extensive research on phosphacycles has provided further evidence for the axial preferences of 2-C1 and 2-OR groups on 1,2,3-dioxaphosphorinan (1 13)95 and 1,2,3-dioxaphosphorinan-2-one (1 14)96 rings though a 2-phenyl group on the latter ring is preferentially eq~atorial.~’ Substitution of ring oxygen atoms for sulphur e.g. (115)reduces the axial preference for a 2-OPh The P-H bonds in (116; R’ = H, R2 = H) and (117),99 and the phenyl group in [116; R’ = 0 or (OMe), R2 = Ph]’oo are also predominantly axial.90 (a) H. Booth and R. U. Lemieux Canad. J. Chem. 1971,49 777; (6)E. L. Eliel L. D. Kopp J. E. Dennis and S. A. Evans jun. Tetrahedron Letters 1971 3409; (c) F. G. Riddell and D. A. R. Williams Tetrahedron Letters 1971 2073; P. J. Halls R. A. Y. Jones A. R. Katritzky M. Snarey and D. L. Trepanier J. Chem. Soc. (B),1971 1320; R. A. Y.Jones A. R. Katritzky and D. L. Trepanier ihid. p. 1300; T. A. Crabb and R. F. Newton Tetrahedron Letters 1971 3361. 91 L. Angiolini R. P. Duke R. A. Y.Jones and A. R. Katritzky Chem. Comm. 1971 1308. 92 A. Rassat and J. Ronzaud J. Amer. Chem. SOC.,1971 93 5041. 93 M. J.Cook A. R. Katritzky and M. Moreno-Mafias J. Chem. SOC.(B),1971 1330. y4 D. N. Harpp and J. G. Gleason J. Org. Chem. 1971 36 1314. 95 M. Haemers R. Ottinger J. Reisse and D. Zimmermann Tetrahedron Letters 1971 461; K. Bergesen and P. Albriktsen Acta Chem. Scand. 1971 25 2257. 96 D. W. White G. K. McEwen R. D. Bertrand and J. G. Verkade J. Chem. SOC.(B) 1971 1454. 97 J.-P. Majoral R. Pujol J. Navech and F. Mathis Tetrahedron Letters 1971 3755. 98 J. R. Campbell and L. D. Hall Chem. and Ind. 1971 1138. 99 J. B. Lambert and W. L. Oliver jun. Tetrahedron 1971,27 4245. loo A. T. McPhail J. J. Breen J. H. Somers J. C. H. Steele jun. and L. D. Quin Chem. Comm. 1971 1020; A. T. McPhail J. J. Breen and L. D. Quin J. Amer. Chem. Soc. 1971,93,2574. Heterocyclic Chemistry-Part (i) Saturated Ring Systems f'i n m-30 o\p/o o\p I 11 4\ ox o// \OPh R2 HS (113) (1 14) (1 15) (1 16) (1 17) 5 Medium-and Large-ring Compounds Syntheses of novel heterocycles and improved routes to known ones have been the subjects of a number of reports this year.These include routes to di- and tetra-hydro-2-benzazepinesand their corresponding 1,3-diones e.g. (118)," and to the benzodiazepinone (1 19) from which the diazacycloundecene ( 120) was obtained.'02 Tetra- and penta-thiepins (l2l)lo3 and (122),lo4 respectively and the first seven-membered cyclic phosphinic acid (123)"' have been pre- pared and the novel pyrrolo-benzodiazocine (124) has been synthesized from (125).'06 In contrast to the behaviour of ethylenediamine with arylideneacetone which gives 14-membered ring products 1,3-diaminopropane with benzylidene- acetone yields (126) rather than a 16-membered ring.lo7 Also unexpected was the photolytic product of (127) ; unlike many hetero-derivatives of 1,3-cyclo- heptadiene (127) failed to collapse to a bicyclic nucleus (of the penicillin type) and either dimerized or rearranged with addition of methanol to (128).'OS G.N. Walker and D. Alkalay J. Org. Chem. 1971 36 461. lo2 M. Davies P. Knowles B. W. Sharp R. J. A. Walsh and K. R. H. Wooldridge J. Chem. Soc.,(C),1971,2449. '03 F. Feher F. Malcharek and K. Glinka Angew. Chem. Znternat. Edn. 1971 10 331. F. Feher and M. Langer Tetrahedron Letters 1971 2125. J. L. Suggs and L. D. Freedman J. Org.Chem. 1971 36 2566. lo6 G. De Martino S. Massa M. Scalzo R. Giuliano and M. Artico Chem. Comm. 1971 1549. lo' K. Hideg and D. Lloyd Chem. Comm. 1971 372. lo* M. F. Semmelhack S. Kunkes and C. S. Lee Chem. Comm. 1971 698. 570 I. D. Blackburne and M. J. Cook X-Ray studies on l-azabicyclo[3,3,3]undecanehydrochloride (129) the free base of which was reported last year,"' confirm the be bc be (bc = boat-chair) conformation suggested for this system and reveal internal strain.' lo Flattening at the nitrogen accounts for the greater acidity relative to quinuclidine hydro- chloride while the free base itself exhibits an electronic absorption uncharac- teristic of a tertiary amine and this again is attributed to distortion. Syntheses conformational studies and transannular interactions between aromatic rings have been the subjects of a number of papers on heterocyclo- phanes.'' Polyether studies have also continued in depth increasing attention being directed towards the examination of complex stability. Stability constants for complexes of cyclic"2 and bicyclic"3 polyethers e.g. (130)and (131),with various cations demonstrate forcibly that ring size or more correctly the fit of log Ann. Reports (B) 1970 67 462. 'lo N. J. Leonard J. C. Coll A. H.-J. Wang R. J. Missavage and I. C. Paul J. Amer. Chem. SOC.,1971,93 4628. ''I S. Akabori K. Shiomi and T. Sato Bull. Chem. SOC.Japan 1971 44 1346; T. Sato M. Wakabayashi K. Hata and M. Kainosho Tetrahedron 1971 27 2737; B. R. Davis and I. Bernal J.Chem. SOC.(B) 1971 2307. H. K. Frensdorff J. Amer. Chem. SOC.,1971 93 600. J. M. Lehn and J. P. Sauvage Chem. Comm. 1971,440. Heterocyclic Chemistry-Part (i) Saturated Ring Systems the cation in the cavity is a key factor in determining complex stability and hence potential selectivity. For monocyclic crowns the optimum ring size for stable + + complexes is 15-1 8 for Na + 1 8 for K ,and 18-2 1 for Cs . Enhanced stability of complexes in organic solvents relative to water is also noted. Large differences in the heats of complexing (130) for the smaller cations Na' and Li' compared with K+,Cs' and NH,' are reported' l4 and these differences are shown to be solvent dependent the largest difference being in DMSO. New nitrogen- and sulphur-containing polyethers have been described.Stability constants for complexes of the alkali and alkaline-earth metals fall on replacing oxygen by N and S but the reverse order is demonstrated for Ag+ complexes where covalent bonds rather than electrostatic forces are probably involved. Crystalline complexes of macrocyclic polyethers with one to six molecules of thiourea have been prepared but the exact nature of these complexes is as yet unknown.'16 Et 7jH5 Et\'\ OH I I p-C,H,C,H,-C-D Me-C-C-Me -+ Me-C-H I /I I OMe C6H5 Et C6H 5 ( 132) (1 33) ( 134) The stereochemical fates of carbanions in the presence of a crown ether have been reported."' Optically active (132) in K0Bu'-Bu'OH undergoes D-H exchange (k,) and racemization (k,) at the relative rate k :k of 46 but in the presence of (130) both rates are enhanced and the ratio k :k is 0.9.Again the base-catalysed decomposition of (133) to (134) proceeds with 90% retention of configuration but in the presence of crown ether the reaction proceeds with 15 7; net inversion. E. M. Arnett and T. C. Moriarity J. Amer. Chem. SOC.,1971 93 4908. C. J. Pedersen J. Org. Chem. 1971,36,254;D. St. C. Black and I. A. McLean Austral. J. Chetri. 1971 24 1377 1391 1401; D. W. Allen P. N. Braunton I. T. Millar and J. C. Tebby J. Chern. SOC.(0, 1971 3454. 'I6 C. J. Pedersen J. Org. Chem. 1971 36 1690. 'I' J. N. Roitman and D. J. Cram J. Amer. Chem. SOC.,1971,93,2231.