Patai S., Rappoport Z. 1997 The chemistry of functional groups. The chemistry of double-bonded functional groups / 1135 122

It is clear, therefore, that the mechanism of aziridination of alkenes using, e.g., 3- acetoxyaminoquinazolinones (240; R D CH3CO) resembles the Bartlett (butterfly) mechanism by which peroxyacids epoxidize alkenes (Scheme 7). Ironically it has been found recently376 that the quinazolinonylnitrene, originally thought to be the reactive intermediate (vide supra), can be generated from 242 and is also an aziridinating agent with a reactivity profile very similar to, but identifiably different from, 242.

N

R N O

O

H O

X

X

SCHEME 7

The characteristics of aziridination using 242 and its congeners can be summarized as follows: (a) reaction with alkenes is stereospecific with retention of the alkene configuration in the aziridine; (b) reaction takes place in good yields with alkenes substituted with electron-donating groups (e.g. alkyl, phenyl, alkoxy) or with electronwithdrawing groups (e.g. CO2R, COR), and with only modest excess of the alkene;

(c) with allylic alcohols, such as cyclohexenol, addition is highly syn-stereoselective (cf

epoxidation with peroxyacids); (d) with chiral 2-substituents on the quinazolinone ring, the aziridination of some prochiral alkenes is highly or completely stereoselective (vide infra);

(e) the exocyclic nitrogen in 242 is pyramidal and inverting slowly on the NMR timescale but fast on the time-scale of the aziridination; (f) the yields of aziridines are greatly increased in many cases by the addition of trifluoroacetic acid or hexamethyldisilazane to the reaction mixture.

The presence of the quinazolinone ring in these aziridinations has been invaluable in allowing inferences to be drawn as to the transition state geometry and mechanism of the reaction377. Thus, for the aziridination of ˇ-trimethylsilylstyrene, the mechanism is believed to be that shown in Scheme 8 with endo-type overlap of the phenyl ring and quinazolinone ring and with an SN2-type displacement of the acetoxy group from the nitrogen running ahead of the N C1 bond formation.

SCHEME 8

Removal of the Q group in the ring-opened aziridines can be accomplished by reductive means (SmI2 or Na/Hg). Alternatively, the aziridine ring can be retained in the removal of Q by the aziridine azirine aziridine interconversion shown in Scheme 8 which takes advantage of the leaving-group ability of the Q group. Using an enantiopure RŁ group CH3CH(OSiMe2But ), the aziridine 248 has been obtained highly diastereoselectively and the aziridine 250 in 83%, e.e.378 380.

VII. ELECTROPHILIC CARBON

A. Addition of ‘C+’

The heats ( Ha) of reaction of diarylmethyl tetrachloroborates with 2-methyl-1- pentene were determined381 by low-temperature calorimetry to be in the range between53.1 kJ mol 1 for (MeC6H4)2CHC BCl4 and 33.0 kJ mol 1 for the better stabilized (MeOC6H4)(MeC6H4)CHC BCl4 . In contrast, the heats of the Lewis-acid-catalysed additions of the corresponding p-substituted diarylmethyl chlorides (Ar2CHCl) are independent of the p-substituent Ha D 86.5 š 2.7 kJ mol 1)381.

Kinetic investigation of the reaction of (p-anisyl)phenylcarbenium tetrachloroborate with methylenecycloalkanes (ring size 3 12 and 15) exhibits correlation of the second-order rate constants with the solvolysis rates of the corresponding cycloalkyl derivatives382.

Kinetic studies of the reactivity of allyltrialkylsilanes towards the p-methoxy substituted diphenylcarbenium ion revealed an increase of the reaction rate by several orders of magnitude compared to olefins lacking the silyl group383. These studies also indicated that the ˇ-silylcarbenium ion is generated in the rate-determining step. The reaction rate, however, is dramatically decreased when one or more alkyl groups on silicon are replaced by chlorine atoms383.

Competition experiments have been carried out to determine the relative reactivities of 23 alkyl chlorides toward allyltrimethylsilane in the presence of ZnCl2. The krel scale has been found to span 11 orders of magnitude from the least reactive 1-adamantyl chloride to the most reactive bis(p-methoxyphenyl)methyl chloride384. By contrast, analogous acetals RCH(OMe)2 exhibited very little differences in reactivity385.

ˇ-(Halosilyl)styrenes undergo dimerization and trimerization on treatment with TfOH via electrophilic addition of the corresponding benzyl cation generated by protonation of the parent molecule386.

The kinetics of the SnCl4-catalysed addition of 1-chloro-3-methyl-2-butene or (E)-2- chloro-3-pentene to isoalkenes (e.g. Me2CDCHCH2CH2CMeClPr) have been shown to be strongly influenced by steric effects387.

B. Addition of ‘C=O’

The addition of CH2(OMe)2 to styrenes 251 254 gives PhCH(OMe)CH2CH2OMe in 96% yield from 252, whereas 252 mostly polymerizes. Addition to 253 is 1.9 slower and affords an equimolar mixture of erythro- and threo-products, whereas the cis-isomer 254 is inert. The reactivities may reflect steric hindrance to planarity in the methylstyrenes, and correspond to the MNDO-calculated heats of formation of the methylstyrene conformers388.

The reaction of substituted vinylferrocenes with chloromethyl alkyl ethers catalysed by Lewis acids proceeds via an ‘exo’ attack to furnish stabilized ferrocenylcarbocations (analogous to benzyl), which are captured by a nucleophile, again in an ‘exo’ fashion. As a result, the whole sequence occurs predominantly with retention of configuration389.

Activated olefins (enol ethers and styrene) smoothly react with acetals in the presence of catalytic amounts of Me3SiCl and SnCl2 or Ph3CCl and (CF3SO3)2Sn to produce the corresponding adducts390.

Transition state structures (chair and twist-boat) for the reaction of formaldehyde with allylborane (255) and allylboronic acid have been located with ab initio calculations at the

acids give cis/trans mixtures, with the cis-isomer 274 being the major product397.

Cationic cyclization of trienone 276 can be controlled by the choice of the reagent. Thus, fluorosulphonic acid in 2-nitropropane at 70 °C afforded a 14:9:1 mixture (70% yield) of cyclic products398, whereas other acidic conditions (95% H2SO4, 85% H3PO4 or SnCl4) gave inferior results398,399.

O

(276)

Molecular mechanics calculations, carried out in order to explain the regioand stereo-chemistry of the transannular cyclization reactions of 19-nor-5,10-secosteroidal cyclodecenone systems, correlate well with experiments400.

Friedel-Crafts cyclization products have been observed for the reaction of 277 with SO3 in the presence of dioxane as a mediator. The reaction has been shown to occur via ˇ-sultone 278, initially formed at 60 °C, which undergoes a spontaneous conversion to the final product 279 at > 20 °C401.

-Aryl participation in bromination of a norbornene derivative has been reported (194 ! 280). Acid opening of the corresponding exo-epoxide proceeds in a similar way402.

Competition of the biomimetic cyclization of epoxides, either with an aromatic ring or with a double bond, has been studied. Evidence for an early transition state has been provided and the biosynthetic implications discussed403.

The biomitetic polyene cyclizations pioneered by Johnson have culminated in stabilizing the cation404,405 and extension to the syntheses of pentacyclic triterpenoids in one step

from an acyclic precursor(!)406 409. Johnson summarized his 50 years of research in a review410.

Br

Imminium ion-vinylsilane cyclizations20, which also belong to this category, are beyond the scope of this chapter.

VIII. ELECTROPHILIC METALS AND ORGANOMETALLICS

A. Silver

Correlation of ionization potentials with reactivities or formation constants of reactions of alkenes with ArSCl, MeCO3H, AgC and Hg2C revealed that additions whose first step is rate-determining are sterically independent, while those with the second step ratedetermining are sterically dependent411.

In analogy with reactions of amines and amides, allenic tosyl carbamates 281 can also be cyclized on action of Ag(I) to afford predominantly or exclusively trans-products 282412. High level of diastereoselectivity (82 99% d.e.) has been reported for the silver(I)-catalysed cyclization of allenic amines 283 (X D CO2Me, CH2OH, CONHMe, SPh S(O)Ph, SePh, PPh2) to give the corresponding 2-vinylpyrrolidine 284. The highest stereoselectivity has been observed in CH2Cl2413,414.

B. Mercury

The PM3 and ab initio calculations have been employed to compare mercuronium and bromonium ions 55 and 52111. Experimental comparison of the mechanism of the oxymercuration and bromination has also been made (see the section on bromination)142.

294 in good yields (70 85%) and with high stereoselectivity ( 95%), which is believed to originate from the favoured, chair-like transition structures 295 or 296419.

Oxymercuration products having an antiperiplanar arrangement of the C HgX and C O bonds (e.g. diaxial as in 298a) are particularly prone to reversion to the olefin (297) when treated with hard reagents, such as NaCl, KBr, CuCl2, CoCl2, HCl etc. The reversal is apparently boosted by the stereoelectronic effect and electrophilic catalysis. By contrast, quenching of the primarily formed organomercurial 298a with soft reagents, such as CuCl, PdCl2, K2PtCl4 etc, reliably affords the desired chloromercurio compound

298b420.

Intramolecular oxymercuration of allene 299 followed by Pd(II)-catalysed carboxymethylation has been found to proceed with excellent cis/trans selectivity (>98:2), presumably via the least hindered transition state 300421.

The previously observed422 preference for the formation of the axial isomer 303 upon mercuration of 302 has now been shown423 not to originate solely from the coordination of Hg(II) by the adjacent ether oxygen. The latter effect appears to be superimposed upon a kinetic preference for the axial product, which is independent of any directing effect. The authors argued that this behaviour may, presumably, originate from an anomeric effect; some inconsistencies in the literature may be attributed to equilibration of the kinetic products. The authors conclude that experiments carried out under kinetic control should preferentially lead to axial isomers423.