Cyclobutanols, ring expansion

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 trimethylsilyl ethers 212 of four-membered 1-alkenyl-1-cyclobutanols rearrange to the ring-expanded 0-mercuriocyclopentanones 213. These can be converted into the a-methylenecyclopentanones 214 through elimination or further expanded by one-carbon atom into cyclohexanones 215 via the Bu3SnH-mediated free radical chain reactions [116]. A similar radical intermediate is suggested to be involved in the ring expansion of a-bromomethyl-fi-keto esters [117]. (Scheme 84)... 

Simiraly, alkynones undergo arylative cyclization with arylboronic acids in the presence of a rhodium catalyst (Equation (49)).400 When acetylenic /3-keto esters are employed as shown in Equation (50), arylative cyclization (formation of cyclobutanols) and subsequent, facile acid-catalyzed bond cleavage take place to give <5-keto esters.401 Ring expansions of cyclic [3-keto esters are also possible according to this reaction. 

The alkoxide generated by KH in THF was believed to be effective in accelerating the vinylcyclobutane ring expansion in the synthesis of 6-membered ring compounds 142). As an example, the cyclobutanol (416) reacted with KH and rearranged to (417), which upon subsequent oxidation, provided (418) 142) in 64.5% yield. The a,P-unsaturated ketone (418) was converted to (—)- 3-selinene (419)142). Similarly, furancyclohexanol (421) could be obtained from the cyclobutanol (420) 142). 

A similar example is the ring expansion of cyclobutanone via l-tris(methylsulfanyl)methyl-cyclobutanol (6) to 2,2-bis(methylsulfanyl)cyclopentanone (7).43 The use of Af,A-diisopropyl-ethylamine is unneccessary in this reaction as the hydroxy group has already been deprotonated with butyllithium. Further examples of this type of reaction can be found in refs 43 and 44. 

The oxidation of cyclopropanecarbinol under Oppenauer conditions using ciiinamaldehyde as oxidant leads to the desired aldehyde contaminated with cyclobutanol, which probably arises from a ring expansion promoted by a complexation of the alcohol with the aluminium atom operating as a Lewis acid. 

An asymmetric [1,2]-Wagner-Meerwein shift has been achieved under Pd catalysis, allowing ring expansion of l-(alkyloxyallenyl)cyclobutanol and simple derivatives to ... 

Another type of carbopalladation is observed in the oxidation of the 2,2-disubstituted alkene attached to the cyclobutanol 104. The shift of the carbon-carbon bond as shown by 105 and ring expansion generate 106. Intramolecular alkene insertion gives the bicyclo[4.3.0]nonane system 107. Finally, 108 is obtained [78],... 

Whatever the case, the formation of the cyclooctenone 320 from the cyclobutanone 317 constituted the first example of a one-step C4 — C8 ring expansion. In the same way, the spirocyclobutanone 266 63,73), was treated with vinylmagnesium bromide to generate a mixture of the diastereomeric cyclobutanols 322 and 323 in 78% yield (ratio 21/79). Each diastereomer, separated by HPLC, individually subjected to KH in THF at room temperature, rearranged cleanly to bicyclo[5.3. l]undec-l(l l)-en-4-one in 80% yield, Eq. (87)161>. 

The reaction of the silyloxypyrroles 47 possessing a chiral substituent at the nitrogen atom, with cyclobutanone in the presence of a Lewis acid, followed by an acid induced ring expansion of the cyclobutanol intermediate 48, offers an asymmetric route to the l-azaspiro[4.4]nonanes 49 in good diastereoisomeric excess <02SL1629>. In this context it might also be interesting to... 

Vinyl-1-cyclobutanols (12) undergo oxidative ring expansion to give cyclopentenones (13 Scheme... 

Ring expansion of cyclopropylcarbinol to cyclobutanol is the basis of an efficient cyclobutene synthesis (equation 25). An elegant approach to polycyclic hydrocarbons is realized by a cascade of cyclopropylcarbiny 1-cyclobutyl rearrangements (equation 26) . 

Cyclopropylmethyl systems containing a carbenium ion stabilizing group at the 1-position of the cyclopropane ring lead to the exclusive formation of cyclobutanols.Thus, 1-methylcy-clobutanol (2 a) was obtained in 90% yield by hydrochloric acid catalyzed ring expansion of (l-methylcyclopropyl)methanol (la). Hydrolysis of 1-phenyl-l-(tosyloxymethyl)cyclo-propane (lb) in 90% acetone/water or dimethyl sulfoxide afforded a quantitative yield of 1-phenylcyclobutanol (2b). 

Alkylidenecyclopentanones Coupling-induced ring expansion of 1-(1-alkynyl)cyclobutanols proceeds in moderate yields. Some of these products are relatively difficult to prepare by other methods. 

In contrast, propargylic cyclopropanols and cyclobutanols undergo ring expansion to form cyclobutanones and cyclopentanones with Au(I) catalysts (equation 10). 

With respect to cyclobutanol, we draw attention to two newer synthetic methods, which were described more recently by Krumpolc and Rocek (1990) and by Salaiin and Fadel (1990) in Organic Syntheses, Both are simple acid-catalyzed ring expansions of cyclopropylmethanol that give cyclobutanol in ca. 80 o and 57yield, respectively. They demonstrate the advantage over the main weakness of deaminations, namely the formation of various by-products which are found in most deaminations. 

Treatment of the l-isopropenyl-2-(3-butenyl)cyclobutanol 508 with Pd(II) afforded the bicyclo[4.3.0]nonane 512. The reaction can be understood by domino -carbon elimination as shown by 509, followed by 5-exo and 6-exo cyclizations of 510 to give 511, and f-H elimination and isomerization afforded 512 [208], A different mechanism based on ring expansion was given before. 

Larock and Reddy obtained the 2-alkylidenecyclopentanone 72 by the reaction of l-(l-alkynyl)cyclobutanol 71 with iodobenzene. The bicyclononanone 74 was obtained from 73. Selective formation of 74 demonstrates that the more substituted bond a in the eyelobutanol 73 undergoes exclusive cleavage (or migration) [8,13]. Larock proposed the mechanism of the reaction of 75 involving ring expansion of 76 to form palladacycle 77 and reductive elimination to give 78. 

Further details of the ring expansion of 1-vinylcyclopropanals and (l-hydroxy-cyclopropyl)methanols to cyclobutanols have appeared. A useful approach to cyclobutanone annelation is the addition of the readily available a-methoxyvinyl-lithium to a cyclic ketone, followed by Simmons-Smith reaction and hydrolytic rearrangement (Scheme 11) ... 

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