Cycloaddition with ketene enolates

Cinchona alkaloid derivatives catalysed the enantioselective 4 + 2-cycloaddition of o-quinones with ketene enolates to produce chiral o-quinone cycloadducts in high ee... 

Scheme 10.4 [4 + 2] cycloaddition of o-benzoquinone imides with ketene enolates. 

One of the most reactive electrophilic alkenes is l,l-dicyano-2,2-bis(trifluoromethyl)ethene which undergoes cycloadditions with enol ethers, thioenol ethers, ketene acetals and thioacetals even at temperatures as low as — 78 °C. The cyclobutancs are formed as the sole products of the reaction.37-38 The reactions arc regiospecific and highly stereoselective even though evidence for zwitterionic intermediates have been obtained. 

The application of chiral auxiliary groups which can be removed after the cycloaddition has met with limited success. The chiral auxiliary can be attached to either the ketene or alkene moiety. In a study of dichloroketene cycloadditions with a series of enol ethers 18, to which a chiral alkoxy group is attached, diastereoselectivities ranged from 55 to 90%,n with the choice of chiral auxiliary being crucial to obtaining the desired diastereoselectivity. 

Reactions of ketenes with electron-rich alkenes proceed more readily than with nonactivated alkenes and in the case of enol ethers, enol sulfides and ketene acetals, the cycloaddition is regiospecific (see Table 6). With tetraalkoxyethene, cycloaddition with the relatively inert ketene can be carried out 124 however, with less activated alkenes the use of metal catalysts such as zinc(ll) chloride is required for cycloaddition of the parent ketene.115... 

Cyclobutenes. This derivative of ketene undergoes [2 + 2]cycloaddition with ethyl propiolate in refluxing methylene chloride to produce the cyclobutene 1 in 65% yield. The ester group activates 1 sufficiently for Diels-Alder addition with the silyl enol ether 2 to give the I I adduct 3 under mild conditions. Hydrolysis of 3 can... 

The DFT study of the 3 + 2-cycloaddition between ketene and TV-silyl-, IV-germyl-, and TV-stannyl-imines shows that the TV-germylimine reaction is a two-step process the TV-stannylimine reaction is a competition between two- and three-step processes whereas the TV-silyl process follows a three-step process44 A new and convenient synthesis of functionalized furans and benzofurans based on 3 + 2-cycloaddition/oxidation has been reported. The cyclization of cyclic 1,3-bis-silyl enol ethers (48) with l-chloro-2,2-dimethoxyethane (49), via a dianion, produced 5,6-bicyclic 2-alkylidenetetrahydrofurans (50), which are readily oxidized with DDQ to 2,3-unsubstituted benzofurans (51) (Scheme 13)45 The Evans bis(oxazoline)-Cu(II) complex catalyses the asymmetric 1,3-dipolar cycloaddition of a -hydroxyenones with nitrones to produce isoxazolidines.46 The... 

Cycloadditions of ketenes with alkenes and alkynes constitute the most popular method for the synthesis of cyclobutanones and cyclobutenones. Unfoitunately, however, this process is truly general only for highly nucleophilic ketenophiles such as conjugated dienes and enol ethers. In general, unactivated alkenes and alkynes fail to react in good yield with either alkyl- or aryl-substituted ketenes, or with ketene itself To circumvent this limitation, dichloroketene is usually employed as a ketene equivalent, since this electrophilic ketene reacts well with many types of unactivated multiple bonds, and the resultant cycloadducts undergo facile dechlorination under mild conditions. ... 

Cinchona alkaloids possess a nucleophilic quinuclidine structure and can perform as versatile Lewis bases to react with ketenes generated in situ from acyl halides in the presence of an acid scavenger. The resulting ketene enolates can react with electrophilic C=0 or C=N bonds to deliver chiral [i-lactones [5] or [i-lactams [6], respectively, in a [2 + 2] cycloaddition manner, which is discussed in Chapter 5 in detail. Gaunt et al. also developed practical one pot cydopropanation processes mediated by the modified cinchona alkaloids via ammonium ylide intermediates [7]. Although the catalytic strategy has been well established, the utilization of ammonium enolate based [4 + 2] cycloaddition is rare probably because of the relative unreactivity of the... 

Following the same strategy, further improvements in similar catalytic asymmetric [4 + 2] cycloaddition reaction have been made by Lectka group. The cyclic 1,4-benzoxazinones 3 (Scheme 10.4) that rely on the highly enantioselective [4 + 2] cycloaddition of o-benzoquinone imides with chiral ketene enolates were efficiently constructed, which can be derivatized in situ to provide a-amino acid derivatives in good to excellent yields and with virtual enantiopurity [9]. 

Unsaturated acyl oxazolidinones 1 undergo enantiospecific [2 + 2] cycloadditions with 1,1-di-methylthioethylene and a catalyst consisting of a 1 1 mixture of diisopropoxytitanium dichloride and the chiral diol 243,44. The cyclobutane 3 is obtained in excellent yield with high enantiomeric excess. This is the first example of the enantiospecific [2 + 2] cycloaddition yielding a cyclobutane using an external chiral auxiliary as a chiral catalyst. Unfortunately, the scope of this reaction is quite limited since it fails with vinyl ethers, silyl enol ethers and ketene silyl acetals. 

By forming adducts with azolecarbenes, cycloaddition of ketenes with imines to form P-lactams is facilitated. Azolecarhenes such as 133 and 134 induce chirahty because in the enolates (initial adducts) the elements of asymmetry can dictate the approach of the reactants. Of particular interest is the reaction between enals and conjugated imines that leads to bicylic structures. 

The methods for generating acyl ketenes (Scheme 7-V) and their subsequent in situ participation in [4 + 2] cycloadditions with a wide range of hetero- or olefinic and acetylenic dienophiles (Scheme 7-VI), including acyl ketenes,185 186,197 carbonyl compounds, 86-188 nitriles,1874,189,191 isocyanates and isothiocyanates,1864,190,191 ketenes,191 imines,1864,1874,191,192 carbo-diimides,l87c 190,191,193 ynamines,194 ketene acetals,1864,195 enol ethers,1864,191,196 and V-sulfinylamines197 have been extensively reviewed.5,9,12 Two reports have detailed the 4-n- participation of allenic ketones in [4 + 2] cycloaddition reactions [Eq. (51)].198,199... 

The [2 -I- 2] cycloaddition of ketenes and imines is an important route to the P-lactam ring (azetidinone), which is a crucial structural feature of the penicillin class of antibiotics. A number of theoretical treatments of this reaction indicate that in solution phase this is a two-step reaction, with the second step being rate determining. The stepwise nature of the reaction is accommodated by the relative stability of both charged moieties, an iminium cation and an enolate anion. 

Even more so than 1,2,4-triazines (see p 441), 1,2,4,5-tetrazines display heterodiene activity in their reactions towards electron-rich, multiply-bonded systems. Enol ethers, enamines, ketene acetals, imido esters, alkynylamines and nitriles undergo [4+2] cycloadditions with inverse electron demand across the ring positions C-3 and C-6 [176]. Olefinic dienophiles lead to diverse products depending on their substituents ... 

Beyond Diels-Alder reactions, a, 3-unsaturated carbene ligands have been applied to [3+2]-cycloadditions with 1,3-dipoles, [27] thermal [2-i-2]-cycloadditions with electron-rich alkenes (enol ethers, ketene acetals) [26] and in intramolecular Pauson-Khand reactions. [28]... 

In contrast with the photochemical cycloaddition reaction of two alkenes, the [2+2] cycloaddition of a ketene and an alkene occurs under thermal conditions. The ketene is formed typically from an acid chloride and a mild base such as EtsN, or from an a-halo-acid chloride and zinc. Cycloaddition with an alkene occurs stereospecifically, such that the geometry of the alkene is maintained in the cyclobutanone product. The regioselectivity is governed by the polarization of the alkene, with the more electron-rich end of the alkene forming a bond to the electron-deficient central carbon atom of the ketene. Thus, the product from cycloaddition of dimethylketene with the enol ether Z-171 is the cyclobutanone m-172, whereas with -171, the isomer trans-lll is formed (3.116). ... 

The ketens used in cycloadditions with cyclopentenes are frequently generated in situ from an acid chloride and a tertiary amine, and the mechanism of these dehydro-halogenations has been investigated. The results suggested that the keten is formed via an acylammonium salt rather than via an enolate. Either species may be trapped under suitable conditions, indicating a complex series of equilibria. 

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