Beckmann ring expansion

Greene and co-workers used a dichloroketene/enol ether cycloaddition and a Beckmann ring expansion as key reactions en route to (+)-preussin [76]. 

Searchable data bases have for some time now simplified the search for the more routine methods of 7-membered ring synthesis. For this reason it seems reasonable to omit yet further examples of cyclisation by cyclocondensation or intramolecular Friedel-Crafts reaction, as well as new examples Schmidt and Beckmann ring expansion reactions, unless specific mechanistic or stereochemical features are of interest. 

Scheme 6 A Beckmann ring expansion approach to tetrahydropyrido[3,2-b]azepin-...

A series of tetrahydropyrido[3,2-l ]azepin-6-ones with a trifluoromethyl group was prepared to study their ADME (absorption, distribution, metabolism, and excretion) profile (14ARK139). The pyridine ring was prepared by a traditional condensation followed by the formation of an oxime (Scheme 6). The key step includes a Beckmann ring expansion of this oxime. 

Nitrones derived from 2-azabicyclo[5.3.0]decane give quinolizidine compounds by photochemical Beckmann rearrangement which implies simultaneous ring expansion and ring contraction reactions. Intramolecular Schmidt reactions in 2(4-azidobutyl)-cyclopentanones also give quinolizidinone derivatives by ring expansion. Examples of both types of reactions are given in Sections 12.01.11.1 and 12.01.11.3, respectively. 

Ozonolysis of alkene 446 in the presence of acetaldehyde afforded diketone 448 through the intermediacy of 447. Ring expansion through Beckmann rearrangement took place when bis-oxime 449 was mesylated and warmed in aqueous tetrahydrofuran (THF). The bis-lactam so formed gave piperidinediol 450 on reduction with lithium aluminium hydride, and this compound was transformed into ( )-sparteine by treatment with triphenylphosphine, CCI4, and triethylamine (Scheme 105) <20050BC1557>. 

Delair and colleagues found that an asymmetric pyrrolidone 344 might serve as a common precursor of (+)-Retronecine 345 and (+)-Amphorogynine A and D (equation 132). The ring expansion was a key and efficient step during the synthetic process and was performed with Tamura s Beckmann reagent. 

During the synthesis of ligands for the vesicular acetylcholine transporter, a octahy-droquinoline nucleus 361 was prepared via a ring-expansion rearrangement followed by a hydride reduction (equation 140). The yield was moderate but only one lactam 360 was produced by the Beckmann rearrangement. 

New azacyclic diterpenoid compounds were also prepared in good yields by ring expansion and only one isomer of the lactam 363 product was obtained (equation 142). However, when the oxime was tosylated, a nitrile compound resulting from ring opening was obtained in good yield (72%) as a result of the Beckmann degradation reaction. 

Acylation of thiochromanones with boron trifluoride and acetic anhydride readily affords (92), which may be elaborated into (93) (equation 36) (79CJC3292), while conversion of the keto function to an oxime (94) permits the formation of the palladium complex (95) as a first step towards functionalization of the aromatic ring (equation 37) (78BCJ3407), or ring expansion by Beckmann rearrangement (equation 38) (76JCS(P1)2343). 

Base-catalyzed ring-expansion of benzisoxazolones (217) provides a general route to 2,2-dialkyldihydro-l,3-benzoxazin-4-ones (218) (78CPB549) and the 2,4-dione (220) can be prepared by a Beckmann rearrangement of the oxime (219) (02CB3647). 2-Thion-4-ones (222) are formed from salicylic acids (221) by treatment with triphenylphosphine diisothiocyanate in dichloromethane at -40 °C (78CI(L)806). 

Beckmann rearrangement of quinuclidin-3-one oxime (103) in the presence of polyphosphoric acid or oleum proceeds with quinuelidine ring expansion and the formation of 3-oxo-l,4-diazabicyclo[3.2.2]-nonane (146).m,m... 

These bicyclo[4.2.0]octanones also undergo aza-ring expansion to lactams. Beckmann rearrangement of the oxime of a typical bicyclic butanone (1) results in an octahydroisoindolone (2), whereas rearrangement of the methylnitrone (3) with tosyl chloride (4, 510 511 6, 598) proceeds in the opposite direction to give an octahydroindolone (4) as the only product.2... 

Activation of the Beckmann rearrangement of the enantiopure spirocyclic keto oximes (—)-(12) and (—)-(13) has been initiated with four acidic promoters.17 In two cases (PPE and PPSE), concerted [1,2]-shift of the anti carbon operates exclusively. This is not the case with PPA or Eaton s reagent, although optical activity is fully maintained in these ring expansions. 

Scheme 11/19. The Beckmann rearrangement as a mean for ring expansion.

The reaction of oxime 385 with polyphosphoric acid results in ring expansion via Beckmann rearrangement leading to the fused 1,4-benzothiazepine derivative 386 (Scheme 207) <1997JHC921, CHEC-III(13.09.10.2)286>. 

The novel heterocyclic system, 5,6,1 l,12-tetrahydrodibenzo[A/][l,4]dia/ocin-6,11-dione 85, was synthesized via ring expansion by Beckmann rearrangement of the morphanthrindine oximes 84, although the details on the substitution pattern R were not reported (Equation 14) <2002SC1929>. 

The Schmidt and Beckmann reactions have been useful in the synthesis of homopiperazinones through ring expansion. In this... 

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