Ethers, vinyl reactions with ketene acetals

Bis-trifluoromethylthioketene 21 undergoes [2+2] cycloaddition reactions with olefins, vinyl ethers, vinyl thioethers and ketene acetals The reaction always proceeds across the C=S bond to give the thiethane derivatives 22. Some of the the cycloadducts are listed in Table 4.16. 

In aldol reactions, especially Mukaiyama aldol reactions, TiIV compounds are widely employed as efficient promoters. The reactions of aldehydes or ketones with reactive enolates, such as silyl enol ethers derived from ketones, proceed smoothly to afford /3-hydroxycarbonyl compounds in the presence of a stoichiometric amount of TiCl4 (Scheme 17).6, 66 Many examples have been reported in addition to silyl enol ethers derived from ketones, ketene silyl acetals derived from ester derivatives and vinyl ethers can also serve as enolate components.67-69... 

The reactions of nitroalkenes (42) with various enols (43b) (vinyl ethers, silyl, and acyl enolates, ketene acetals) have been studied in most detail (110, 111, 125—154). As a mle, these reactions proceed smoothly to give the corresponding nitronates (35f) in yields from high to moderate. As in the reactions with enamines, the formation of compounds (44b) is attributed to the ambident character of the anionic centers in zwitterionic intermediates analogous to those shown in Scheme 3.43. 

The reactivity of the produced complexes was also examined [30a,b]. Since the benzopyranylidene complex 106 has an electron-deficient diene moiety due to the strong electron-withdrawing nature of W(CO)5 group, 106 is expected to undergo inverse electron-demand Diels-Alder reaction with electron-rich alkenes. In fact, naphthalenes 116 variously substituted at the 1-, 2-, and 3-positions were prepared by the reaction of benzopyranylidene complexes 106 and typical electron-rich alkenes such as vinyl ethers, ketene acetals, and enamines through the Diels-Alder adducts 115, which simultaneously eliminated W(CO)6 and an alcohol or an amine at rt (Scheme 5.35). 

In order to carry out this reaction by a one-pot procedure, we examined the same complexation reaction in the presence ofaketene acetal, which led us to the discovery of the novel reaction pathways described below [32]. Thus, treatment of o-ethynylphenyl ketone 104 with a catalytic amount of W(CO)5(thf) in the presence qf4equiv of 1,1-diethoxyethylene at rt gave a novel polycyclic compound 120 in good yield as a single stereoisomer. Both vinyl ethers and ketene acetals can be employed as the electron-... 

The reaction of alkenyl alkyl ethers and ketene acetals with PX3 (X = Cl or Br) has been reported to occur readily in the presence of an organic base and to result in the electrophilic substitution of a vinyl hydrogen atom with the PX2 group. Thus, (2-alkoxyalkenyl)-, (l-bromo-2-alkoxyalkenyl)- and (2,2-dialkoxyalkenyl)-phosphorus dichlorides and dibromides were obtained in 70-98% yield. The reaction proceeds regio- and stereo-selectively and is believed to involve formation of a cyclic phosphirenium ion.74... 

Chiral dienes have proved to be less popular in asymmetric Diels-Alder reactions than their chiral dienophile counterparts. This is primarily a result of the problem of designing a molecule that incorporates a chiral moiety, such as the formation of a chiral isoprenyl ether or vinyl ketene acetal.187-190 In addition, diastereoselectivities often are not high,54 191-199 as illustrated by the cycloaddition of the chiral butadiene 5 with acrolein (Scheme 26.4). Improved stereoselection is observed through the use of double asymmetric induction, although this is a somewhat wasteful protocol.35,54 177 200... 

Later, the dimethylphenylsilyl adduct 75 d was not only converted to the vinyl-ketene acetal 81 by a Wittig-Horner reaction via the ester 80, but also by reduction of 80 to the aldehyde 84 followed by silylation of the corresponding anion to the silylenol ether 85. Vinylcyclohexenes without terminal substitution (e. g., 83) was prepared via an alcohol derived from 80 or 84 [73,74]. The least substituted diene 83 was alternatively prepared from the triflate 82 in a Stille coupling with trialkylvinyl stannane [75] (Scheme 24), a reaction also used by Toshima etal.[76]. 

In addition to alkenes or compounds with strained double bonds, 1,2,4-triazines react readily with electron-rich dienophiles such as enol ethers, enamines, enaminones, vinyl silyl ethers, vinyl sulfides, vinyl acetate, and ketene derivatives (see also Ilouben-Weyl, Vol. E7b, p 471 ff). It has been shown195,403,404 that oxo compounds and catalytic amounts of amines can be used instead of enamines however, water formed in the reaction can result in the formation of side products.403... 

Aromatic and aliphatic acyl isocyanates participate in a similar range of [4 + 2] cycloadditions although [2 + 2] and simple addition reactions often are observed. The acyl isocyanate substituents may determine or alter the observed course of the reaction, and the substituent effects have been detailed in extensive reviews.7,71 Observed [4 + 2] cycloadditions of acyl isocyanates with selected olefins, p-quinones, allenes, the carbon-carbon double bond of ketenes, electron-rich acetylenes, imines, dianils, ethy-lenediimines, enamines, enol ethers, ketene acetals, carbodiimides, azirines, and vinyl sulfides have been described.7 0 The reaction of aromatic acyl isocyanates with carbodiimides is not a simple, direct [4 + 2] cycloaddition but proceeds by a kinetic [2 + 2] cycloaddition followed by a subsequent rearrangement to provide the observed [4 + 2] cycloadduct [Eq. (40)].97... 

Early extensive accounts of the 4v participation of a,/)-unsaturated carbonyl compounds in [4 + 2] cycloadditions detailed their reactions with electron-deficient dienophiles including a,/3-unsaturated nitriles, aldehydes, and ketones simple unactivated olefins including allylic alcohols and electron-rich dienophiles including enol ethers, enamines, vinyl carbamates, and vinyl ureas.23-25 31-33 Subsequent efforts have recognized the preferential participation of simple a,/3-unsaturated carbonyl compounds (a,/3-unsaturated aldehydes > ketones > esters) in inverse electron demand [4 + 2] cycloadditions and have further explored their [4 + 2]-cycloaddition reactions with enol ethers,34-48 acetylenic ethers,48 49 ke-tene acetals,36-50 enamines,4151-60-66 ynamines,61-63 ketene aminals,66 and selected simple olefins64-65 (Scheme 7-1). Additional examples may be found in Table 7-1. 

Formamidine acetate was prepared in similar high yield by a similar procedure but with glacial acetic acid as solvent.804 A A-Disubstituted formamidine and acetamidine derivatives have been obtained analogously from orthoesters and alkylamines in the presence of glacial acetic acid805 or boron trifluoride etherate 806 In the reaction of orthoesters with secondary amines in the presence of toluenesulfonic acid the formation of ketene aminals (alkyl l -amino-vinyl ethers) was also observed.807... 

Ketene diethyl acetals, which are more nucleophilic than vinyl ethers, add to a wide array of sulfenes to produce [2 + 2] cycloadducts36 39,207. The reaction of meth-anesulfonyl chloride with ketene diethyl acetal gave 3,3-diethoxythietane 1,1-dioxide, which can be hydrolyzed to 3-oxothietane 1,1-dioxide by concentrated hydrochloric acid (equation 97)207. The reaction of methanesulfonyl chloride with two equivalents of ketene... 

The LUMOdiene HOMOalkene interaction for butadiene and methyl vinyl ether is lower than the comparable HOMOdiene-LUMOaikene interaction in dienes bearing an electron-withdrawing group. In many cases, but not all, this leads to the inverse electron demand reaction mentioned above. Fleming uses the example of azonia salt 86, which reacted with diethyl ketene acetal to give 87. Similar reaction with allyl alcohol gave 88, and acrylonitrile gave 89.97a in all cases, the reaction proceeded to 75% completion, and it is clear from the relative rates of reactions provided with each transformation that the electron-rich alkenes reacted faster. The concept of inverse electron demand applies to a Diels-Alder reaction that is controlled by the LUMO of the diene and the HOMO of the alkene, which usually means that an electron-rich alkene reacts faster than an electron-poor alkene, the opposite of what is normally observed (see above). 

With a cyclic substrate, for example in which three or more atoms of the allyl vinyl ether are constrained in aring, then the boat-shaped transition state maybe favoured. Formation of the silyl ketene acetal from the lactone 295 and rearrangement on warming gave the carboxylic acid 296 (3.190). The reaction occurs via a boatshaped transition state and was used in a synthesis of the sesquiterpene widdrol. 

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