Cycloaddition mixed

The interaction of acid chlorides (167 X = Cl) with imines in the presence of bases such as triethylamine may involve prior formation of a ketene followed by cycloaddition to the imine, but in many cases it is considered to involve interaction of the imine with the acid chloride to give an immonium ion (168). This is then cyclized by deprotonation under the influence of the base. Clearly, the distinction between these routes is a rather fine one and the mechanism involved in a particular case may well depend on the reactants and the timing of mixing. Particularly important acid chlorides are azidoacetyl chloride and phthalimidoacetyl chloride, which provide access to /3-lactams with a nitrogen substituent in the 3-position as found in the penicillins and cephalosporins. 

The initial product formed when methyl vinyl ketone is mixed with an enamine [such as N,N-dimethylisobutenylamine (10)] is the dihydropyran (11) from a 1,4 cycloaddition (ll,20a,20b). The chemical reactions that the dihydropyran undergoes indicate that it is readily equilibrated with the cyclobutane isomer 12a and zwitterion 12 (11). Treatment of adduct 11 with phenyllithium gives cyclobutane 13, possibly via intermediate 12a (11). 

The substituents at C-2, C-3 within diene 97 and those at C-1, C-2 within dienophiles 98-100 are electronically and/or sterically equivalent with respect to diene and dienophile reaction centers, respectively, and therefore cycloaddition should not display regiochemical bias in the absence of orientational effects. The Diels-Alder reactions of 97 prepared in situ with 98-100 gave an excess of 101 (Scheme 4.19) [70b], which are the expected regioisomers if the reagents react in their preferred orientations within a mixed micelle with an ammonium head group at the aggregate-water interface and the remainder in the micelle interior. 

Dipolar [3 + 2] cycloadditions are one of the most important reactions for the formation of five-membered rings [68]. The 1,3-dipolar cycloaddition reaction is frequently utihzed to obtain highly substituted pyrroHdines starting from imines and alkenes. Imines 98, obtained from a-amino esters and nitroalkenes 99, are mixed together in an open vessel microwave reactor to undergo 1,3-dipolar cycloaddition to produce highly substituted nitroprolines esters 101 (Scheme 35) [69]. Imines derived from a-aminoesters are thermally isomerized by microwave irradiation to azomethine yhdes 100,... 

Since the number of domino processes which start with a Diels-Alder reaction is rather large, we have subdivided this section of the chapter according to the second step, which might be a second Diels-Alder reaction, a 1,3-dipolar cycloaddition, or a sigmatropic rearrangement. However, there are also several examples where the following reaction is not a pericyclic but rather is an aldol reaction these examples will be discussed under the term Mixed Transformations . 

Thermally induced intra-intermolecular criss-cross cycloaddition of nonsymmetrical azines 363 in the presence of phenyl isocyanate provides the corresponding products of the mixed criss-cross cycloaddition 364 (Scheme 55) <2002TL6431>. Two different reaction mechanisms, intra-intermolecular and inter-intramolecular, of the mixed criss-cross cycloaddition with opposite sequence of reaction steps are possible. Quantum chemistry calculations suggest the intra-intermolecular mechanism as the most probable mechanism of this reaction <2004CCC231>. 

Eq. 17 is meant to represent the possibility for a concerted formation of oxetane product. A problem that always exist in cycloadditions is the question of whether the reaction takes place by a two-step biradical reaction pathway or through a concerted mechanism. Such questions have not even been resolved for purely thermal reactions. 4> A recent speculation on this point proposes almost universal concertedness for all cycloaddition reactions. 79> In that work, mixed stereochemistry in the products of [2+2] cycloaddition reactions is generally attributed to a mixture of two concerted reactions, suprafacial-suprafacial, and supra-facial-antarafacial. It will be seen later that the PMO calculations generally do not support this idea. A mixture of biradical and concerted reactions is in better agreement with experimental facts. 

Ir-complexes also demonstrate catalyhc achvity in the intermolecular [2+2+2] cycloaddition of three monoalkynes, when Takeuchi examined the mixed cyclotrimerization of two alkynes. In this situation the choice of ligand was shown to determine the excellent chemoselechvity for example, when the Ir-dppe complex was used, 2 1 cycloadducts of DM AD and mono- or disubstituted alkynes were obtained, but when Ir-F-dppe (l,2-bis[bis(pentafluorophenyl)phosphino]eth ane) one was used, a 1 2 cycloadduct of DMAD and l,4-dimethoxybut-2-yne was obtained (Schemes 11.7 and 11.8) [15]. A regioselective cyclotrimerizahon of three alkynes was achieved by [lrH(cod)(dppm)] (bis(diphenylphosphino)methane), and 1,2,4-triarylbenzenes were obtained exclusively (Scheme 11.9) [16]. 

Regioselective syntheses of 1,3,5-unsymmetrically substituted benzenes (309) are catalyzed by Pd(dba)2/PPh3 mixed alkyne/diyne reactants give mixtures containing homocoupled and mixed products (24 21 from HC CPh + HC=CC= CC Hn). The probable mechanism involves oxidative addition to the Pd(0) center, insertion of the second diyne into the Pd—H bond, reductive coupling and subsequent jr-complexation of this product to Pd(0), followed by Diels-Alder cycloaddition of the third diyne and elimination of product. 

However, when pyridyliminophosphorane (306a) is treated with phenyl isocyanate or isothiocyanate (Scheme 110), mixed carbodiimides are obtained, which are capable of an intermolecular Diels-Alder reaction resulting in triazine 308. The cycloaddition occurs specifically with one C = N double bond of the carbodiimide serving as the dienophile (77ZC371). 

Thermal or catalytic cyclodimerization of iminoboranes is obviously a [2 -I- 2]-cycloaddition (Section IV). A mixture of two different iminoboranes may be stabilized by formation of three different cyclodimers. If the relative stability of the two iminoboranes, however, differs distinctly, the mixed cyclodimer will be formed preferentially by... 

A very simple chiral Lewis acid, prepared by mixing optically pure BINOL with 3 equiv of Me3Al, catalyzes the [4+2] cycloaddition of A-hydroxy-A-phenylacry-lamine with cyclopentadiene at 0°C in high yield (>96%) and a fairly good level of enantioselectivity (91% ee). Facile conversion of the products to the corresponding alcohols or aldehydes makes the hydroxamic acid intermediates particularly useful (Scheme 12.14). ... 

Treatment of bis(chloromethylether) 54 with a mixed-manganese/lead system generated a reactive intermediate equivalent to the carbonyl yhde depicted in 55. Intermediate 55 behaved as a 1,3-dipole undergoing cycloaddition with a variety of dipolarophiles including A-tosylaldimines such as 56, resulting in the formation of oxazolidine 57 in 73% yield. 

There are very few examples of photolysis being used for preparation of a carbonyl ylide. The Dittami protocol follows work completed from his lab with aryl vinyl sulfides. Photolysis, followed by cycloaddition, led to the cycloadduct 305 in excellent yield and stereoselectivity. If the aryl vinyl ether 304 was subjected to irradiation in a mixed solution of toluene-methanol at 366 nm rather than a single solvent of toluene, cyclized product was obtained, but no cycloadduct was formed. If a simple phenyl aryl ether was subjected to the same tandem conditions, the cyclized product was generated, but no cycloadduct was detected. 

Zinc chloride-doped natural phosphate was shown to have catalytic behavior in the 1,3-dipolar cycloadditions of nucleoside acetylenes with azides to form triazolonucleosides <99SC1057>. A soluble polymer-supported 1,3-dipolar cycloaddition of carbohydrate-derived 1,2,3-triazoles has been reported <99H(51)1807>. 2-Styrylchromones and sodium azide were employed in the synthesis of 4(5)-aryl-5(4)-(2-chromonyl)-1,2,3-triazoles <99H(51)481>. Lead(IV) acetate oxidation of mixed bis-aroyl hydrazones of biacetyl led to l-(a-aroyloxyarylideneamino)-3,5-dimethyl-l,2,3-triazoles <99H(51)599>. Reaction of 1-amino-3-methylbenzimidazolium chloride with lead(fV) acetate afforded l-methyl-l/f-benzotriazole <99BML961>. Hydrogenation reactions of some [l,2,3]triazolo[l,5-a]pyridines, [l,2,3]triazolo[l,5-a]quinolines, and [l,2,3]triazolo[l,5-a]isoquinolines were studied <99T12881>. 

Fig. 30 Energy diagram showing the major configurations that contribute to any cycloaddition reaction, DA, D+A, and 3D 3A. For allowed reactions, DA and D+A mix, thereby lowering the activation barrier. For forbidden reactions, mixing of DA and D+A is precluded by symmetry...

Cyclobutadienes represent very reactive alkenes that undergo both [2 + 2] as well as [4 + 2] cycloadditions. Both the cyclodimerizations, mixed [2 + 2] cycloadditions and Diels-Alder reactions of these reactive species have been reviewed (see Houben-Weyl, Vols. 4/4, p 231 and E 17 f, Section 10B). In most instances the initially formed cyclodimer is tricyclo[4.2.0.02-5]octa-3,7-diene (36) and has the all cis-syn configuration. This is attributed to the concerted [4n -I- 2n] cycloaddition mechanism in which stereochemical control is affected by secondary orbital interactions. 

Although hole-catalyzed (cycloaddilions involving radical cation intermediates) and PET (photochemical electron transfer) mixed [2 -I- 2] cycloadditions have been reported from electron-rich alkenes, the only report of a cyclodimerization is that of (E)-4-(prop-l-enyl)anisole which gives stereoisomeric mixtures of the head-to-head dimers 1 and 2.12... 

Cyclodimerization of unsymmetrically substituted butatricncs such as 12 give both head-to-head and hcad-to-tail cycloaddition products. The structure of the head-to-head dimer was confirmed by its independent synthesis from the mixed cycloaddition of cumulenes 8 and 10,21 22 These dimerizations proceed by discrete nickel cyclopentanes which was established by the isolation of the 2-bispyridinenickel complex of the l.l,4,4-tetramelhylbuta-l,2,3-triene dimer.23 4-Radialenes with extended conjugation, potential organic conductors and semiconductors, have been prepared by similar methods as illustrated by the examples below.24,25... 

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