Organic reaction mechanisms - 1998

F

H

S

H H

OBn

H

SCHEME 93

rearrangement reaction of various glycals with glycerol derivatives436 and other O-nucleophiles.437 The synthesis of a new aminopolysaccharide (288) having an amino-ketose structure, has been achieved438 utilizing the thermal polymerization of 6-amino-6-deoxy-D-glucose (287) in the presence of acetic acid. The novel Lewis acid-catalysed rearrangement of a sugar-base hybrid to afford an anhydronucleoside has been reported,439 and the attempted intermolecular addition of malonyl radicals to 1 , 2 -unsaturated nucleosides has been found to lead to furanones.440 An unusual ring contraction–rearrangement has been observed441 during the attempted fluorination of thiofuranose derivatives with diethylaminosulfur trifluoride (DAST). Scheme 93

outlines the proposed mechanism for this transformation which is considered to proceed by the regioselective opening of a transient episulfonium ion.

The observed acid-catalysed conversion of complestatin (289) into chloropeptin L (291) has been envisioned442 as proceeding through a cyclopropyl intermediate (290) (see Scheme 94). An intramolecular oxygen-transfer reaction illustrated in Scheme 95 has been proposed443 to explain hydroxylation of the aromatic nucleus, viz. formation of (292), during the course of a modified Polonovski reaction on galanthamine.

H

HO N

O

CH

D

CH

(291)

SCHEME 94

Rearrangements Involving Electron-deficient Heteroatoms

An ab initio study of the effects of both substituents and solvents on the Beckmann rearrangement has been undertaken444 and the potential-energy surfaces corresponding to the Beckmann rearrangement of a series of aliphatic and cyclic alkanone oximes have been explored445 using density functional theory. The vapour-phase Beckmann rearrangement of cyclohexanone oxime to -caprolactam, catalysed by mesoporous molecular sieves, has been studied,446 and a weakly acidic borosilicate has also been utilized447 as a catalyst in the above reaction. The non-catalytic Beckmann rearrangement of cyclohexanone oxime to -caprolactam in supercritical water has been reported,448 and a comparison has been made of the Beckmann rearrangement of

acids via a Beckmann rearrangement has been developed454 [see (295) to (296)]. The syntheses of 6-O-methylazithromycin and its aza-ketolide analogue have been achieved455 by carrying out the Beckmann rearrangement of the readily available 9(E)-6-O-methylerythromycin oxime. The reduction of aromatic and cyclic O-(t - butyldimethylsilyl) aldoximes and ketoximes with various reducing agents has been investigated and an attempt has been made to explain the effect of substituents on the novel rearrangement [(297) to (298)] that occurs with a borane–tetrahydrofuran complex.456

A re-evaluation of the Hofmann rearrangement in electron-deficient systems has been undertaken.457 A detailed study of the discrete intermediates, and the sensitivity of the intermediates and products to reagents and to each other in the Hofmann rearrangement of N -α-tosylasparagine, has led to a process that produces 2-(S)- (tosylamino)-β-alanine on a large scale.458

It has been demonstrated that the thermal reaction of a series of alkynylor alkenoylcontaining acyl azides such as (299) involves competition between intramolecular azide cycloaddition and a Curtius rearrangement. Apparently the substituent R plays a key role in determining the competition between the two possible routes.459 It has been shown460 that a silicon group situated at the β-position with respect to an acyl azide group enhances the rate of the Curtius rearrangement by a factor of three, whereas a γ -silyl substituent has a marginal influence. These observations have lent support to the proposition that, during the concerted intramolecular rearrangement of an acyl azide to an isocyanate, an electron-deficient centre at the migration origin is created. An efficient route for the asymmetric synthesis of α, α- disubstituted α-amino acid derivatives, starting from readily available epoxy silyl ethers, has been developed461 using the Curtius rearrangement as a key step (see Scheme 96).

COMe

R

N

N3

S

O

(299)

SCHEME 97

The neutral alkali metal salts of benzohydroxamic acids have been found to undergo an unprecedented rearrangement to N ,N -diarylureas.462 A side reaction, producing β-alanine derivatives by way of a Lossen rearrangement, has been observed to accompany the hydrolysis of alkyl succinimidyl carbonates463 in basic aqueous buffers (see Scheme 97). The development of a modified Lossen rearrangement, whereby

N -(t -butyloxycarbonyl)-O-methanesulfonylhydroxamic acids have been converted into protected amines in good yield, has been described464 (see Scheme 98).

A successful synthesis of the tetrahydropyran-protected hydroperoxide (300; 1-18O) using the Baeyer–Villiger strategy has been reported.465 Experimental evidence has been obtained466 to support the fact that, in the Baeyer–Villiger oxidation and Criegee rearrangement, a stereoelectronic effect directs the migratory aptitude, and it is the bond antiperiplanar to the dissociating peroxide bond that always migrates, even when it is electronically disfavoured from doing so.

NHCO2CH2Ph

SCHEME 98

O O

OH

(300)

O = 18O

Rearrangements Involving Organometallic Compounds

An ab initio investigation of the transition state for the Lewis acid-associated migration of an alkyl group from boron to an α-dichloro-carbon in a non-racemic boronic ester has been carried out.467 The calculated transition state has shown that it is important to have the non-participating chlorine atom anti to the metal, e.g. as in (301). The

SCHEME 99

stereoselectivity is then dictated by placing the metal on the least-hindered side of the oxygen, trans to the R group of the ester. This combination places the Lewis acid in the sterically least hindered position.

2-Aminocyclonona-1,8-dienyl carbene complexes (302) in solution have been found to undergo ring contraction of the nine-membered ring to give (2-amino- cycloheptenyl)alkenyl carbene complexes (303) which are subsequently transformed into tetrahydroazulenes (304) by elimination of the metal unit468 (see Scheme 99), and (cyclobutenyl)carbene tungsten complexes (305) have been shown to rearrange

d2[{p-But -calix[4]-(O4)}W] fragment assists a variety of ethylene rearrangements

reducing conditions. Quantum-mechanical calculations have shown that471 that two energetically nearly degenerate pathways are possible for the rearrangement of tungsten–acetylene complexes (307) to the energetically higher lying vinylidene complexes (310). The direct [1,2]-hydrogen migration was found to proceed via a transition state (308) which has a non-planar C2H2 moiety. The alternative pathway involves the alkynyl(hydrido)metal complex (309). Complexes of the chiral bis(oxazoline) 2,6-bis[(4S)-isopropyloxazoline-2-yl]pyridine (311; M = Mo or W), in which the ligand is restricted to a bidentate bonding mode, have been found to be