Donor-acceptor-substituted derivatives

An application of donor-acceptor-substituted derivatives such as 7 not only effects cyclopropane cleavage under milder conditions, but also generates products having... 

Usually, application of donor-acceptor-substituted derivatives not only affects ringopening under milder conditions, but also generates products containing additional functionality for further operations (equations 5, 7, 8). Reductive or electrocyclic ringopening can afford 1,4-dienes (equation 9) or allyl substituted products (equation 10). 

Stimulated by extensive research activities on donor/acceptor substituted stilbenes, Mullen and Klarner have reported a donor/acceptor substituted poly(4,4 -biphenyl-diylvinylene) derivative (85) in which the NR2 donor and CN acceptor substituents are located on the vinylene unit [111]. The synthesis is based on a C-C-coupling reaction of in situ generated carbanion functions with a (pseudo)cation function, followed by a subsequent elimination of MeSH with formation of the olefinic double bond. 

An alternative strategy for selective intermolecular G-H insertions has been the use of rhodium carbenoid systems that are more stable than the conventional carbenoids derived from ethyl diazoacetate. Garbenoids derived from aryldiazoacetates and vinyldiazoacetates, so-called donor/acceptor-substituted carbenoids, have been found to display a very different reactivity profile compared to the traditional carbenoids.44 A clear example of this effect is the rhodium pivalate-catalyzed G-H insertion into cyclohexane.77 The reaction with ethyl diazoacetate gave the product only in 10% yield, while the parallel reaction with ethyl phenyldiazoacetate gave the product in 94% yield (Equation (10)). In the first case, carbene dimerization was the dominant reaction, while this was not observed with the donor/acceptor-substituted carbenoids. 

The C-H insertion a to nitrogen can be extended to acyclic systems. The reaction with jY-benzyl-iV-methylamine is an excellent example of the interplay between steric and electronic effects. The benzylic position would be electronically the most activated, but due to the steric crowding, the C-H insertion occurred exclusively at the iV-methyl site (Equation (27)).86 This is a general method for generating a-aryl-/5-amino acid derivatives. The N,N-dimethylamino group undergoes a very favorable C-H insertion by the donor/acceptor-substituted carbenoids. Indeed, the reaction is so favorable that double C-H insertion was readily achieved to form the elaborated -symmetric amine 10 (Equation (28)).87... 

The elimination reactions of /l-acetoxy sulfones 114 to give the donor-acceptor-substituted allenes 115 by a Julia-Lythgoe process are less conventional (Scheme 7.18) [157]. A new one-step synthesis of allene-l,3-dicarboxylates 118 from acetone derivatives 116 was developed by the use of 2-chloro-l,3-dimethylimidazolinium chloride 117 [158, 159]. This elimination of water follows also the general Scheme 7.17 if a derivative of the enol, resulting from 116, is assumed as an intermediate for an elimination step. More complex processes of starting materials 119 furnished allenyl ketones 120 in high yields [160-162]. 

The most spectacular application of the donor/acceptor-substituted carbenoids has been intermolecular C-H activation by means of carbenoid-induced C-H insertion [17]. Prior to the development of the donor/acceptor carbenoids, the intermolecular C-H insertion was not considered synthetically useful [5]. Since these carbenoid intermediates were not sufficiently selective and they were very prone to carbene dimerization, intramolecular reactions were required in order to control the chemistry effectively [17]. The enhanced chemoselectivity of the donor/acceptor-substituted carbenoids has enabled intermolecular C-H insertion to become a very practical enantioselective method for C-H activation. Since the initial report in 1997 [121], the field of intermolecular enantioselective C-H insertion has undergone explosive growth [14, 15]. Excellent levels of asymmetric induction are obtained when these carbenoids are derived... 

One of the problems associated with thermal cyclodimerization of alkenes is the elevated temperatures required which often cause the strained cyclobutane derivatives formed to undergo ring opening, resulting in the formation of secondary thermolysis products. This deficiency can be overcome by the use of catalysts (metals Lewis or Bronsted acids) which convert less reactive alkenes to reactive intermediates (metalated alkenes, cations, radical cations) which undergo cycloaddilion more efficiently. Nevertheless, a number of these catalysts can also cause the decomposition of the cyclobutanes formed in the initial reaction. Such catalyzed alkene cycloadditions are limited specifically to allyl cations, strained alkenes such as methylenccyclo-propane and donor-acceptor-substituted alkenes. The milder reaction conditions of the catalyzed process permit the extension of the scope of [2 + 2] cycloadditions to include alkene combinations which would not otherwise react. 

Donor-acceptor-substituted vinylcyclopropanes such as (203) have been shown to undergo thermal ring enlargement to functionalized cyclopentene derivatives (204) at... 

An analytical structure-(hyper)polarizability relationship based on a two-state description has also been derived [49]. In this model a parameter MIX is introduced that describes the mixture between the neutral and charge-separated resonance forms of donor-acceptor substituted conjugated molecules. This parameter can be directly related to BLA and can explain solvent effects on the molecular hyperpolarizabilities. NMR studies in solution (e.g. in CDCl3) can give an estimate of the BLA and therefore allow a direct correlation with the nonlinear optical experiments. A similar model introducing a resonance parameter c that can be related to the MIX parameter was also introduced to classify nonlinear optical molecular systems [50,51]. 

Chemistry of cyclopropane derivatives, which combine different sorts of activating substituents, has less definitely been investigated and their synthetic potentials have only recently been explored. Whereas geminally donor-acceptor-substituted systems 6 were treated in preceeding contributions to this series 5 6 7), this review will be confined to vicinally activated compounds 7. 

A very intriguing system 31 with donor-acceptor substitution pattern can be obtained by an intramolecular cyclopropanation 22). The tricyclic product 31 permits several ring cleavage reactions (Scheme 3), some of which are not known for less strained cyclopropanes. All methods lead to oxabicyclo[2.2.2]octane derivatives. Thus, hydro-genolysis proceeds under relatively mild conditions breaking the bond between the donor and the acceptor substituted carbons exclusively. 

Vicinally donor-acceptor-substituted olefins usually are rather unreactive species. Nevertheless cyclopropanation of 2,2-dimethyl-3(2 H)-furanone 70 could be executed with dimethyl oxosulfonium methylide as a methylene source. The bicyclic compound 71 is formed in modest yield accompanied by the spiro epoxide as a second product in almost equal amounts. Carbinols 72 derived from 71 by alkyl lithium addition can be nitrosated and photolyzed to suffer a Barton fragmentation. The resulting y-oxoaldehydes are directly cyclized to afford the 2-substituted cyclopentenones 73 in good yield 41. ... 

Threefold donor-acceptor-substituted benzene derivatives like [109] (Ledoux et al., 1990) or [110] (Verbiest et al., 1994 Wolff et al., 1996b Wortmann et al., 1997 Wolff and Wortmann, 1998) show better performance for [109], only powder data and computational results are available. Both are of the hexasubstituted type, but strong intra- and inter-molecular hydrogen bonds provide for planarity. The discrepancy (Bredas et al., 1992) between the observation of a moderate powder SHG efficiency of [109] and the published (Cady and Larson, 1965) centrosymmetric crystal structure (PT) has been resolved. The powder consists of two polymorphs, with the second one adopting the close to optimal space group P3i (Voigt-Martin et al., 1996,1997). 

The discovery of the dual fluorescence of the simple donor-acceptor substituted benzene derivative 4JV,iV-dimethylaminobenzonitrile (DMABN) by Lippert et al. [1] and the subsequent model compound studies by Grabowski et al. [2-6] including rigidized and pretwisted compounds such as MIN, TMABN and CBQ gave birth to the idea of Twisted Intramolecular Charge Transfer (TICT) states. 

Similar transformations using diphenylphosphine oxide and diethyl thio-phosphite have also been performed. Rhodium prolinate second generation complex Rh2(S-TISP)2 has been used as a very effective catalyst promoting conversion of dimethyl aryldiazomethyl phosphonates (192) into the stereo-chemically defined donor/acceptor substituted rhodium carbenoid intermediates. The latter are capable of cyclopropanation of various styrene derivatives affording cyclopropylphosphonates (193) in high yields (85-96%), diastereo-selectivity (>98% de), and enantioselectivity (76-92% ee) ( Scheme 52). A... 

A group with donor quality can also be created by deprotonation of an a-acceptor-substituted derivative combined with the presence of a suitable acceptor or leaving group it brings about ring cleavage as depicted in equations 11 and 12. 

Buchert, M., Reissig, H. U. Rearrangement of donor-acceptor-substituted vinylcyclopropanes to functionalized cyclopentene derivatives. Evidence for zwitterionic intermediates. Liebigs Ann. Chem. 1996, 2007-2013. 

Donor-acceptor-substituted cyclopropane derivatives and their application in organic synthesis (with many examples of synthesis of various heterocyclic compounds including drugs 03CRV1151. 

Similarly, 4-halobutanoate (see Table 2) and 5-halo-l-(trimethylsilyl)alkynyl derivatives (Scheme 2) can undergo the base-catalyzed cyclopropane ring-forming reaction. With alkoxy substituents in the starting materials, synthetically versatile donor-acceptor substituted cyclopropanes (see Section l.B.2.1.4.) are thus formed. 

Ethyl 4-(/cr/-butyldimethylsiloxymethyl)-l-(trimethylsiloxy)bicyclo[3.1.0]hexane-6-carboxy-late (1) reacted with chlorotrimethylsilane to give the desilylated 2-(ethoxycarbonylme-thyl)cyclopentanone derivative 2 by cleavage of the original donor-acceptor-substituted bond. ... 

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