Cyclobutanones, 4 + 2-cycloaddition

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]. 

There is some spectral evidence that acylation of enamines of cyclic ketones with acid chlorides having an a-hydrogen in the presence of triethylamine proceeds via the ketene and subsequent cycloaddition (84). The intermediate cyclobutanone is then opened to give the enamino ketone which is hydrolyzed to the 2-acyl cyclohexanone. In the case of enamines of larger cyclic ketones the alternate mode of the cyclobutanone opening predominates, with the formation of ring-expanded 1,3-diketones upon... 

Abstract The photoinduced reactions of metal carbene complexes, particularly Group 6 Fischer carbenes, are comprehensively presented in this chapter with a complete listing of published examples. A majority of these processes involve CO insertion to produce species that have ketene-like reactivity. Cyclo addition reactions presented include reaction with imines to form /1-lactams, with alkenes to form cyclobutanones, with aldehydes to form /1-lactones, and with azoarenes to form diazetidinones. Photoinduced benzannulation processes are included. Reactions involving nucleophilic attack to form esters, amino acids, peptides, allenes, acylated arenes, and aza-Cope rearrangement products are detailed. A number of photoinduced reactions of carbenes do not involve CO insertion. These include reactions with sulfur ylides and sulfilimines, cyclopropanation, 1,3-dipolar cycloadditions, and acyl migrations. 

Staudinger observed that the cycloaddition of ketenes with 1,3-dienes afforded cyclobutanones from a formal [2+2] cycloaddition [52] prior to the discovery of the Diels-Alder reaction. The 2+2 cycloadditions were classified into the symmetry-allowed 2+2 cycloaddition reactions [6, 7], It was quite momentous when Machiguchi and Yamabe reported that [4+2] cycloadducts are initial products in the reactions of diphenylketene with cyclic dienes such as cyclopentadiene (Scheme 11) [53, 54], The cyclobutanones arise by a [3, 3]-sigmatropic (Claisen) rearrangement of the initial products. 

Ketenes have cnmnlative bonds and can undergo [2+2] cycloaddition reactions across C=C and C=0 bonds. Interestingly, most of the prodncts obtained are cyclobutanones rather than oxetanes. Thermal [2+2] cycloaddition reactions in the pseudoexcitation band occur between electron donors and acceptors. Alkenes are donors while ketenes are acceptors. In contrast to the experimental observations. 

Cycloaddition reactions of ketenes with alkenes have long been known to give cyclobutanones [123] and to proceed with retention of the configurations [124], The reactions were classified into the symmetry-allowed cycloaddition reactions... 

The cyclobutanone is the important aspect. We shall want to make it by ketene cycloaddition (the key reaction) (Chapter T 33) and this we can do after an aldol disconnection. 

Cycloadditions of ketenes and alkenes have synthetic utility for the preparation of cyclobutanones.163 The stereoselectivity of ketene-alkene cycloaddition can be analyzed in terms of the Woodward-Hoffmann rules.164 To be an allowed process, the [2ir + 2-tt] cycloaddition must be suprafacial in one component and antarafacial in the other. An alternative description of the TS is a 2irs + (2tts + 2tts) addition.165 Figure 6.13 illustrates these combinations. Note that both representations predict formation of the d.v-substituted cyclobutanone. 

Ketenes are especially reactive in [2 + 2] cycloadditions and an important reason is that they offer a low degree of steric interaction in the TS. Another reason is the electrophilic character of the ketene LUMO. As discussed in Section 10.4 of Part A, there is a large net charge transfer from the alkene to the ketene, with bond formation at the ketene sp carbon mnning ahead of that at the sp2 carbon. The stereoselectivity of ketene cycloadditions is the result of steric effects in the TS. Minimization of interaction between the substituents R and R leads to a cyclobutanone in which these substituents are cis, which is the stereochemistry usually observed in these reactions. 

The preparation of cyclobutanones can easily be realized by using the thermal-[2 + 2]cycloaddition of haloketenes to olefinic compounds (Eq. (2))49). 

Enantioselective [2 + 2 cycloaddition.2 The chiral allylic ether (1), prepared from (lS,2R)-( + )-2-phenylcyclohexanol, undergoes enantioselective cycloaddition with dichloroketene to furnish, after one crystallization, optically pure (-)-2. This cyclobutanone after ring expansion and exposure to chromium(II) perchlorate gives... 

Cyclobutanones (11, 560-561). Ketenimium salts are more reactive than ke-tenes in [2 + 2] cycloadditions with alkenes to prepare cyclobutanones. The salts are readily available by in situ reaction of tertiary amides with triflic anhydride and a base, generally 2,4,6-collidine. The cycloaddition proceeds satisfactorily with alkyl-substituted alkenes and alkynes, but not with enol ethers or enamines.1... 

We break the C4-C6 bond, and we form C3-C8 and C4-C9. The formation of the latter two bonds and the fact that we re forming a cyclobutanone suggests a [2+2] cycloaddition between a ketene at C3=C4=0 and the C8=C9 n bond. We can generate the requisite C3=C4 n bond by electrocyclic ring opening of the cyclobutene ring in the S.M. 

The reaction of enynes with Fischer-type carbene complexes can also lead to the formation of cyclobutanones (Figure 2.23) [315]. The mechanism for this reaction is likely to be rearrangement of the intermediate, non-heteroatom-substituted vinylcarbene complex to a vinylketene, which undergoes intramolecular [2 -i- 2] cycloaddition to form the observed cyclobutanones. 

Cycloaddition of ketene and imine to form 3-lactam. Other coupling partners for ketene also include olefin to give cyclobutanone and carbonyl to give 13-lactone. 

The stereoselective [2+2] cycloaddition between ketenes and enolethers can be used as a key step in the construction of y-butyrolactones (Scheme 14) [45], if the resulting cyclobutanones can subsequently undergo ring enlargement by a regioselective Baeyer-Villiger oxidation. 

Using (-)-lOO [46] as a chiral auxiliary tethered to the enolether, one face of the alkene can be specifically blocked by a n-n interaction of the phenyl rest for the [2 r5+2 r ] cycloaddition with a ketene [47], resulting in the highly diastereoselective formation of the cyclobutanone 102 (Scheme 15). The observed regio- and stereoselectivity is in accord with the stereochemical predictions made on the basis of the Woodward-Hoffmann... 

Fig. 6.6. HOMO-LUMO interactions in the [2 + 2] cycloaddition of an alkene and a ketene. (a) Frontier orbitals of alkene and ketene. (b) [2ks + 2na Transition state required for suprafacial addition to alkene and antarafacial addition to ketene, leading to R and R in cis orientation in cyclobutanone products, (c) [2ns + (2ns + 271,)] alternative transition state.

The Cj - and 54-symmetric tetraesters of tricyclo[3.3.0.0 ]octane (430 and 431) have been prepared by oxidation of diene 429 To access the parent hydrocarbon (435), acid chloride 432 was transformed to the derived ketene which undergoes intramolecular [2+2] cycloaddition The resulting cyclobutanone (433) serves as precursor to perester 434 whose thermal decomposition proceeds with chain transfer in competition with cleavage The unique arrangement of the carbon atoms in 435 is such that the smallest rings are all five-membered. The highly symmetric structure may be viewed as a constrained cisoid bicyclo[3.3.0]octane (as well as the symbol of NATO). 

Ketene acetals and thioacetals can be used as ketene equivalents in cyclobutanone synthesis in situations where ketene to alkene cycloadditions are inefficient such as in the case of electron-deficient alkenes.14 Although thermal cycloadditions of ketene acetals and thioacetals with electron-deficient alkenes have been observed (see Section 1,3.2.1.), such cycloadditions proceed more efficiently and under milder conditions with metal catalysts. Efficient cycloadditions between ketene dimethyl acetal and alkenes substituted by a single electron-withdrawing group have been reported.15... 

Ketene thioacetals can also be used as ketene equivalents in the preparation of cyclobutanones and cyclobutanes. Boron trifluoride catalyzes the [2 + 2] cycloaddition of 2-[(l-pyrro-lidinyl)mcthylene]-1,3-dithiane (39) with dimethyl maleate (40).17 Although the cycloadduct is obtained in good yield, stereochemical integrity is not maintained and the thermodynamically most stable isomer predominates. 

An attractive synthesis of cyclobutanones involves the titanium(IV) chloride catalyzed cycloaddition of mixed ketene acetals 46 with divinylsulfone (49) used as an ethene equivalent, The primary 2-vinylsulfonylcyclobutanones 50 formed can be desulfonylated to the corresponding cyclobutanones 51 in the presence of an aluminum amalgam.20... 

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