Ketene intramolecular

Similarly, the acetal 146 can undergo a thermal Wolff rearrangement to afford the intermediate ketene. Intramolecular nucleophilic attack of the acetal oxygen onto the ketene forms the zwitterion 147. Subsequent C-0+ bond cleavage and cyclization then furnishes dimethyl l,3-dimethoxy-l//-isochromen-4-yl phosphonate in excellent yield (Scheme 47) <1998T6457>. 

In the presence of a double bond at a suitable position, the CO insertion is followed by alkene insertion. In the intramolecular reaction of 552, different products, 553 and 554, are obtained by the use of diflerent catalytic spe-cies[408,409]. Pd(dba)2 in the absence of Ph,P affords 554. PdCl2(Ph3P)3 affords the spiro p-keto ester 553. The carbonylation of o-methallylbenzyl chloride (555) produced the benzoannulated enol lactone 556 by CO, alkene. and CO insertions. In addition, the cyclobutanone derivative 558 was obtained as a byproduct via the cycloaddition of the ketene intermediate 557[4I0]. Another type of intramolecular enone formation is used for the formation of the heterocyclic compounds 559[4l I]. The carbonylation of the I-iodo-1,4-diene 560 produces the cyclopentenone 561 by CO. alkene. and CO insertions[409,4l2]. 

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cyclo addition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-cataly2ed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41—43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cyclo additions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

The most efficient intramolecular secondary processes competing with the acyl-alkyl diradical recombination in five-membered and larger cyclic ketones are hydrogen shifts resulting in the disproportionation of the diradical to either ketenes or unsaturated aldehydes [cf. (5) (4) (6)]. 

Although these reactions are thus closely related to the acyl-alkyl diradical disproportionation to ketenes, the stereospecificity of (55) -> (56) and (57) -> (58) shows that these hydroxyketones cannot proceed through free radicals capable of rotating about single bonds prior to the intramolecular hydrogen... 

When a hydrogen atom is present next to the carboxyl group, an intramolecular dehydration may occur, resulting in a ketene Two highly fluonnated, sulfur-con-taming ketenes were prepared this way [67, 84] (equations 54 and 55)... 

The hetero Diels-Alder [4+2] cycloaddition (HDA reaction) is a very efficient methodology to perform pyrimidine-to-pyridine transformations. Normal (NHDA) and Inverse (IHDA) cycloaddition reactions, intramolecular as well as intermolecular, are reported, although the IHDA cycloadditions are more frequently observed. The NHDA reactions require an electron-rich heterocycle, which reacts with an electron-poor dienophile, while in the IHDA cycloadditions a n-electron-deficient heterocycle reacts with electron-rich dienophiles, such as 0,0- and 0,S-ketene acetals, S,S-ketene thioacetals, N,N-ketene acetals, enamines, enol ethers, ynamines, etc. 

It is instructive to note that the intramolecular [2+2] cycloaddition process should benefit from the presence of the cis C1-C2 double bond in 14. Indeed, the cis C1-C2 double bond is expected to facilitate the key [2+2] cycloaddition event by bringing into proximity the reactive ketene moiety and the C5-C6 olefin and by... 

Of the many interesting and productive stages in Corey s synthesis of ginkgolide B, it is the intramolecular ketene-olefin [2+2] cycloaddition step that is perhaps the most impressive (see 14—>13). The conversion of 14 to 13 is attended by the formation... 

Alkoxycarbene complexes with unsaturation in the alkyl side chain rather than the alkoxy chain underwent similar intramolecular photoreactions (Eqs. 10 and 11) [60]. Cyclopropyl carbene complexes underwent a facile vinyl-cyclopropane rearrangement, presumably from the metal-bound ketene intermediate (Eqs. 12 and 13) [61]. A cycloheptatriene carbene complex underwent a related [6+2] cycloaddition (Eq. 14) [62]. 

Both alcohols and phenols add to ketenes to give carboxylic esters (R2C=C= O+ROH —> R2CHC02R). This has been done intramolecularly (with the ketene end of the molecule generated and used in situ) to form medium- and large-ring lactones. In the presence of a strong acid, ketene reacts with aldehydes or ketones (in their enol forms) to give enol acetates. 

The primary delocalization occurs from tz of alkenes to of ketenes (Scheme 25). The pseudoexcitations occur through the HOMO-HOMO and LUMO-LUMO interactions (Scheme 4). The HOMO of the donors is n as usual, whereas the HOMO of the acceptors is not but The HOMO-HOMO interaction occurs between the C=C bonds of alkenes and ketenes and promotes the reaction accross the C=C bond of ketenes. The important DA configuration is the intramolecular... 

The cycloaddition between a nitrilimine 319 and an aroyl substituted heterocyclic ketene aminal 318 has been found to be stepwise, involving an initial nucleophilic addition of 318 to 319 followed by intramolecular cyclocondensation of the intermediate 320 providing fully substituted pyrazole 321 (Eq. 36) [92]. When Ar was the 2,4-dinitrophenyl group, the intermediate 320 was isolable and required forcing conditions (xylene, reflux, 10 h) to undergo cyclization ... 

Nevertheless, a more traditional approach to the stabilization of carbenes and the investigation of their spectral properties deals with the direct generation of carbenes in low-temperature matrices, e.g. by the photolysis of diazo-compounds or ketenes. The method allows stabilization of carbenes in their ground electronic state, prevents intramolecular isomerization and also facilitates direct spectroscopic monitoring of their chemical transformations in low-temperature matrices. 

In the first step, catalyst 64c attacks ketene 66 to form a zwitterionic enolate 71, followed by Mannich-type reaction with imine 76 (Fig. 40). A subsequent intramolecular acylation expels the catalyst under formation of the four-membered ring. Utilizing 10 mol% of 64c, N-Ts substituted (3-lactams 77 were prepared from symmetrically as well as unsymmetrically substituted ketenes 66, mainly, but not exclusively, with nonenolizable imines 76 as reaction partners [96]. Diastereos-electivities ranged from 8 1 to 15 1, yields from 76 to 97%, and enantioselectivities from 81 to 94% ee in the case of aliphatic ketenes 66 or 89 to 98% ee for ketenes bearing an aromatic substituent. Applying complexes 65 or the more bulky and less electron-rich 64b, ee values below 5% were obtained. 

Intramolecular ketene cycloadditions are possible if the ketene and alkene functionalities can achieve an appropriate orientation.170... 

Some trends in relative reactivity for intramolecular ketene cycloadditions have been examined by internal competitions.172 For example, 12 gives exclusively 13, pointing to a preference for five-membered rings over six-membered ones. 

Scheme 6.8 gives some examples of ketene-alkene cycloadditions. In Entry 1, dimethylketene was generated by pyrolysis of the dimer, 2,2,4,4-tetramethylcyclobutane-l,3-dione and passed into a solution of the alkene maintained at 70° C. Entries 2 and 3 involve generation of chloromethylketene by dehydrohalo-genation of a-chloropropanoyl chloride. Entry 4 involves formation of dichloroketene. Entry 5 is an intramolecular addition, with the ketene being generated from a 2-pyridyl ester. Entries 6, 7, and 8 are other examples of intramolecular ketene additions. 

The stereoselectivity of silyl ketene acetal Claisen rearrangements can also be controlled by specific intramolecular interactions.246 The enolates of a-alkoxy esters adopt the Z-configuration because of chelation by the alkoxy substituent. 

Entry 6 is analogous to a silyl ketene acetal rearrangement. The reactant in this case is an imide. Entry 7 is an example of PdCl2-catalyzed imidate rearrangement. Entry 8 is an example of an azonia-Cope rearrangement, with the monocylic intermediate then undergoing an intramolecular Mannich condensation. (See Section 2.2.1 for a discussion of the Mannich reaction). Entry 9 shows a thioimidate rearrangement. 

The a,( -unsaturated aldehyde 452 is generated from the unstable spiro-oxetane 451, and hydrogen abstraction from the aldehydic C-H bond by 3449 gave a triplet radical pair 453 and 454. Intersystem crossing and radical recombination followed by intramolecular nucleophilic attack of the hydroxyl group toward the ketene functionality furnish the diastereomeric products 54 and 55 (Scheme 102) <20000L2583>. 

Wolff rearrangement of a-diazoketones to give ketenes or subsequent products is an often used synthetic procedure the scope and limitations of which are well established 13 390), so that only a few new features of this reaction need to be considered here. Concerning its catalytic version, one knows that copper, rhodium and palladium catalysts tend to suppress the rearrangement390). A recent case to the contrary is provided by the Rh2(OAc)4-catalyzed decomposition of ethyl -2-diazo-3-oxopent-4-enoates 404 from which the p,y-unsaturated esters 405 are ultimately obtained via a Wolff rearrangement 236). The Z-5-aryl-2-diazo-3-oxopent-4-enoates undergo intramolecular insertion into an aromatic C—H bond instead (see Sect. 4.1). 

Claisen rearrangement. As for the mechanism, the reaction begins with intramolecular cyclopropanation the resulting bicyclo[2.1.0]pentan-2-one then undergoes fragmentation to a p,y-unsaturated ketene which finally is trapped by the added alcohol to afford a p,y-unsaturated ester (Scheme 41). The intermediates could be observed in selected cases. 

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