A ring expansion

Fig. 1. Biosynthesis of cephalosporins and cephamycins. a, Cephalosporium acremonium, b, Penicillium chjsogenum, c, Streptomjces clavuligerus-, d, Streptomjces lipmanir, e, Streptomjces wadajamensis, REX is a ring expansion en2yme (deacetoxycephalosporin C synthethase).

Treatment of a cyclic ketone with diazomethane is a method for accomplishing a ring-expansion reaction. For example, treatment of cyclohexanone with diazomethane yields cycloheptanone. Propose a mechanism. 

Ready extrusion of sulfur dioxide from fused thiirane dioxides is well known and was observed in the formation of pyrazoles from 19b and diazoalkanes6,179. A ring expansion... 

ROCM also offers the possibility of a ring expansion. Tadano and co-workers used this approach successfully as a key step in the total synthesis of (H-)-mycoep-oxydiene, though only in moderate yield [165] (Scheme 3.17). 

Rasor and Tischer (1998) have brought out the advantages of enzyme immobilization. Examples of penicillin-G to 6-APA, hydrolysis of cephalospwrin C into 7-ACA, hydrolysis of isosorbide diacetate and hydrolysis of 5-(4-hydroxy phenyl) hydantom are cited. De Vroom (1998) has reported covalent attachment of penicillin acylase (EC 3.51.11) from E.Coli in a gelatine-based carrier to give a water insoluble catalyst assemblase which can be recycled many times, and is suitable for the production of semi-synthetic antibiotics in an aqueous environment. The enzyme can be applied both in a hydrolytic fashion and a synthetic fashion. 6-APA was produced from penicillin-G similarly, 7-ADCA was produced from desa acetoxycephalosporin G, a ring expansion product of penicillin G. 

The key cyclization in Step B-2 was followed by a sequence of steps that effected a ring expansion via a carbene addition and cyclopropyl halide solvolysis. The products of Steps E and F are interesting in that the tricyclic structures are largely converted to tetracyclic derivatives by intramolecular aldol reactions. The extraneous bond was broken in Step G. First a diol was formed by NaBH4 reduction and this was converted via the lithium alkoxide to a monomesylate. The resulting (3-hydroxy mesylate is capable of a concerted fragmentation, which occurred on treatment with potassium f-butoxide. 

A combination of a Pd-catalyzed nucleophilic substitution by a phenol and a ring expansion was described by Ihara and coworkers [127] using cis- or trans-substituted propynylcyclobutanols 6/l-262a or 6/l-262b. The product ratio depends on the stereochemistry of the cyclobutanols and the acidity of the phenol 6/1-263. Thus, reaction of 6/l-262b with p-methoxyphenol 6/1-263 (X = pOMe) led exclu-... 

The strategy employed in studies aiming at the synthesis of the spiro segment of halichlorine (see also Section 12.01.11.4) involved a ring expansion in indolizidine 264. The double bond of this compound was cleaved by ozonolysis yielding compound 265, which was cyclized to quinolizidine derivative 266 in the presence of base (Scheme 56) <2004TL2879>. 

Figure 5.23 SAND can be used to modify amine-containing molecules, and then photo-initiate crosslinking to another amine-containing molecule via a ring-expansion process. The conjugates may be disrupted by reduction of the cross-bridge disulfide with DTT.

Figure 5.31 ASIB can react with sulfhydryl-containing molecules through its iodoacetate group to form thioether linkages. Subsequent exposure to UV light causes a ring-expansion process to occur, creating a highly reactive dehydroazepine intermediate that can couple to amine-containing molecules.

Figure 5.32 APDP can modify sulfhydryl-containing compounds through its pyridyl disulfide group to form disulfide bonds. Its phenyl azide end then can be photolyzed with UV light to couple with nucleophiles via a ring-expansion process. The disulfide group of the crosslink can be selectively cleaved using Dll.

Additionally, the authors chose 3-chloropropionyl chloride as the immobilized building block in order to carry out a ring-expansion approach, which led to the generation of a 14-member library of thioxotetrahydropyrimidinones [85, 86], The initially prepared polymer-bound chloropropionyl ester was efficiently transformed into the corresponding diamines by transamination utilizing several primary amines. These diamine intermediates could also be obtained by treatment of the pure polymeric support with acryloyl chloride and subsequent addition of the appropriate amines (Scheme 7.74). 

Vinylcyclopropanes represent particularly useful functionality. They do permit a ring expansion to cyclobutanes via the cyclopropylcarbinyl cation manifold (Eq. 9). Equally important, such systems suffer smooth thermal rearrangement to cyclopen-... 

The construction of cyclopentanones can take several avenues based upon the concepts evolving from use of small ring conjunctive reagents. A very simple one is a-cuparenone (183) which can be thought to derive by a ring expansion of a cyclobutyl carbinyl system as in 184 (Scheme 8) 110,1U). If X. is an anion stabilizing... 

The unexpected variety found in cationic polymerizations is well illustrated by recent findings concerning the polymerization of dioxolan by perchloric acid. Gresham91 had been unable to find end-groups in polydioxolans made under anhydrous conditions and concluded that they were cyclic. His result has been confirmed by studies made with anhydrous perchloric acid as catalyst [92]. Since it is extremely unlikely that complete absence of chain ends can be achieved by a cyclization of long chains, and from other evidence, we concluded that the polymerization takes place without formation of chain ends, i.e. by a ring expansion mechanism ... 

The propagation for cyclic formals also involves a solvated oxonium ion and a highly polar monomer [10, 12]. Since under optimum conditions the polymers are essentially free from any kind of end-group (except very small amounts of -OH) Plesch and Westermann [36, 37] concluded that they must be formed by a ring-expansion mechanism, involving a 4-centred transition state ... 

However, for a variety of reasons it seems extremely unlikely that the same mechanism is applicable to the polymerisation of cyclic formals and acetals. One reason is that these compounds cannot be co-polymerised with cyclic ethers another is that the polymers are predominantly cyclic, with the number of end-groups far smaller than the number of growing chains. One mechanism which has been proposed and which accounts for most of the observations involves formation of an oxonium ion (X) from the initiator and the monomer, and a subsequent propagation by a ring-expansion reaction (see 13). 

Since the carboxonium ion has been eliminated as a possible propagating species, one is left with two alternatives which we may call the Keele and the Mainz theories. Plesch and Westermann [6, 8] have suggested that the cyclic formals polymerise by a ring-expansion mechanism, in which no free end is ever formed. This is illustrated in Reaction (B), where Y = H if the initiator is a protonic acid, and Y = Et if the initiator is a... 

The second theory is the Keele theory proposed by Plesch and Westermann [2, 4, 5] in which the propagation reaction is seen as a ring-expansion during which no free chain-end is formed ... 

According to the Keele theory the primary reaction between the perchloric acid and the monomer is also (1), but thereafter the growth is by a ring-expansion reaction (4) in which no free end is ever formed this goes by way of a four-centred transition state and gives the cyclic product (IV) ... 

The present author holds the view that since the number of end-groups is always much smaller than the number of polymer molecules, a ring-expansion mechanism, analogous to reaction (4), is the most plausible. This matter will be discussed in Section 5. 

Diphenylcarbene also undergoes a ring expansion of the above kind. When it was generated in the gas phase at 350°C/3Torr, small quantities of tetraphenylethylene, the triphenylheptafulvene 563 and the diphenylheptafulvalene 564 were formed in addition to fluorene (565), which was obtained in 29% yield. As illustrated in... 

In the protonation of l-(l -methoxy-T,2 -propadienyl)-2-cyclobuten-l-ols 93, the a,/3-unsaturated enones 94 formed by protonation can be further converted to 5-hy-droxy-5-vinyl-2-cyclopentenones 96 by a ring-expansion reaction under the action of H+ [44],... 

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