Alkyl-substituted adducts

A radically different course is followed when the reaction of 2-alkyl-substituted thiazoles is periormed in methanol or acetonitrile (335), 2 1 adducts containing seven-membered azepine rings (91) are being formed in which two of the original activated hydrogen atoms have altered positions (Scheme 55). A similar azepine adduct (92) was obtained by... 

The TCNQ molecule in [TR(bzim)]2-TCNQ is sandwiched between two units of [ J,-N, C -bzimAu]3 in a face-to-face manner so that it is best represented by the formula (7t-[ J,-N, C -bzimAu]3)( j,-TCNQ)(7t-[p-N, C -bzimAu]3). The cyanide groups clearly are not coordinated to the gold atoms. The distance between the centroid of TCNQ to the centroid of the AU3 unit is 3.964 A. The packing of [TR(bzim)]2-TCNQ shows a stacked linear-chain structure with a repeat pattern of-(Au3)(Au3)(p-TCNQ) (Au3)(Au3)(p-TCNQ)- an ABBABB repeat The complex [TR(bzim)]2-TCNQ contains two very short intermolecular Au Au distances of 3.152 A (identical for the two aurophilic bonds). The intermolecular Au Au distance is even shorter than the intramolecular distances in the starting compound, which are 3.475, 3.471, and 3.534 A. The adjacent AU3 units in [TR(bzim)]2-TCNQ form a chair-type structure rather than the face-to-face (nearly eclipsed) pattern reported in Balch s studies of the nitro-9-fluorenones adducts with the trinuclear Au(I) alkyl-substituted carbeniate complexes. 

A study of the stereochemistry and secondary isotope effects for the 2 + 2-cycloaddition of alkyl-substituted buta-1,3-dienes with Ceo indicates the formation of an open biradical intermediate in the rate-determining step leading to the cycloadduct (18) (Scheme 5). The addition of benzyne to C70 produces four isomeric monoadducts. One of these adducts is the first example of an adduct of a 5-6 ring fusion where the ring-fusion bond remains intact. 

Relative rates of reactions of dialkylbenzenes are not easily explained. The presence of p-alkyl-substitution generally causes a large decrease in rate, whereas o-xylene. which should have the same inductive effects as p-xylene, reacts very rapidly. Possibly this rapid reaction of o-xylene is caused by an intramolecular transmetalation between the carbanion adduct with ethylene and the remaining methyl group [Reaction (22)]. 

As shown by Table 7 above, the chiral titanium catalyst-MS 4A system is widely applicable to the reactions of a variety of dienophiles and dienes when a suitable alkyl substituted benzene is employed as a solvent, and synthetically important Diels-Alder adducts are prepared in high enantioselectivity by the present catalytic process. 

This work has been extended from aryl and alkyl substituted systems (42) (R = aryl, alkyl) to analogues where R is an amino group, so giving access to synthetic equivalents of the nonstabilized amino nitrile ylides (45). Adducts were obtained in good-to-moderate yield with A-methyhnaleimide (NMMA), DMAD, electron-deficient alkenes and aromatic aldehydes (27,28), and with sulfonylimines and diethyl azodicarboxylate (29). Similarly the A-[(trimethylsilyl)methyl]-thiocarbamates (46) undergo selective S-methylation with methyl triflate and subsequent fluorodesilylation in a one-pot process at room temperature to generate the azomethine ylides 47. 

Access to alkyl substituted derivatives of the homotropylidene complexes is provided via the >j4-tropone iron complex by reaction with diazoalkanes, followed by mild thermolysis of the 3+2 py razoline adduct to give the corresponding homotropone complexes (equation 149)217,218. The 8,8-dimethyl derivative was used as starting material for the preparation of the fluxional ( 5-2,8,8-trimethylbicyclo[5.1.0]octa-2,4-dienylium)Fe(CO)3 cation complex219. More recently (homotropone)Fe(CO)3 was used for the synthesis of unique chiral 1,2-homoheptafulvene iron complexes220 221. 

Peptide a-oxo acids 1 (R4=H), a-oxo esters 1 (R4= alkyl or substituted alkyl), and a-oxo-amides 2 (R5=R6=H, alkyl, substituted alkyl, aryl, and/or heteroaryl) are potent reversible inhibitors for cysteine and serine proteases (Scheme 1).[1 9 Their inhibitory potency is the result of their enhanced electrophilic a-carbonyl functional group that can better compete with the substrate in the formation of a tetrahedral adduct with the cysteine or serine residue at the protease active site. In the case of peptide a-oxo esters and a-oxoamides, the extension in PI and beyond gives the inhibitors additional interactions with the protease at the corresponding sites. 

Electrophilic addition of Cl., and In tn nlkenes is similar in mechanism to the electrophilic addition of Br0.46 The rate of chlorination in acetic acid is second-order, first-order each in olefin and in chlorine.47 Predominantly anti addition to alkyl-substituted double bonds occurs, indicating that a chloronium ion is formed.48 Further evidence for the chloronium ion is that addition of hypo-chlorous acid to double bonds is not entirely regiospecific. For example, addition to propene gives 91 percent of the Markownikoff product 29, and 9 percent of the anti-Markownikoff product, 30. Phenyl-substituted alkenes give a mixture of syn and anti adducts with Cl2 as they do with Br2.49... 

Michael reactions of chiral lithioenamines of p-oxo esters with dimethyl alkylidenemalonates were studied.173-176 Especially the a-alkyl-substituted compounds (161) and (163), derived from L-valine t-butyl ester, afford, after hydrolysis, the adducts (162) and (164), respectively, diastereoselectively and with high ee (Scheme 57).175 In the presence of TMS-C1, even weaker acceptors like acrylates or MVK were shown to react.176 A somewhat related diastereoselective 1,4-addition, followed by a Pictet-Spen-gler-type cyclization, allows the preparation of compound (165 Scheme 58),177 a central intermediate for the synthesis of several alkaloids.177-178... 

A large number of accurate rate constants are known for addition of simple alkyl radicals to alkenes.33-33 Table 2 summarizes some substituent effects in the addition of the cyclohexyl radical to a series of monosubstituted alkenes.36 The resonance stabilization of the adduct radical is relatively unimportant (because of the early transition state) and the rate constants for additions roughly parallel the LUMO energy of the alkene. Styrene is selected as a convenient reference because it is experimentally difficult to conduct additions of nucleophilic radicals to alkenes that are much poorer acceptors than styrene. Thus, high yield additions of alkyl radicals to acceptors, such as vinyl chloride and vinyl acetate, are difficult to accomplish and it is not possible to add alkyl radicals to simple alkyl-substituted alkenes. Alkynes are slightly poorer acceptors than similarly activated alkenes but are still useful.37... 

The sulfide fraction of non-biodegraded petroleums usually contains a complement of n-alkyl substituted sulfides, thiolanes and thianes, in addition to the terpenoid class. In the biodegraded Alberta oil sand bitumens, however, n-alkyl substituted sulfides are absent. The two classes of sulfides can be separated by thiourea adduction, the n-alkyl-containing molecules being adducted. Raney nickel reduction of the Bellshill Lake sulfides (1 11 yielded a series of n-alkanes showing a distribution quite similar to that of the n-alkanes in the saturate fraction of this oil. In some oils the thiolane and thiane concentrations are commensurate, e.g. Houmann, Figure 13 in others, the concentration of thianes may be small compared to thiolanes. 

Besides simple enones and enals, less reactive Michael acceptors like /3,/3-disubstituted enones, as well as a,/3-unsaturated esters, thioesters, and nitriles, can also be transformed into the 1,4-addition products by this procedure.44,44a,46,46a The conjugate addition of a-aminoalkylcuprates to allenic or acetylenic Michael acceptors has been utilized extensively in the synthesis of heterocyclic products.46-49 For instance, addition of the cuprate, formed from cyclic carbamate 53 by deprotonation and transmetallation, to alkyl-substituted allenic esters proceeded with high stereoselectivity to afford the adducts 54 with good yield (Scheme 12).46,46a 47 Treatment with phenol and chlorotrimethylsilane effected a smooth Boc deprotection and lactam formation. In contrast, the corresponding reaction with acetylenic esters46,46a or ketones48 invariably produced an E Z-mixture of addition products 56. This poor stereoselectivity could be circumvented by the use of (E)- or (Z)-3-iodo-2-enoates instead of acetylenic esters,49 but turned out to be irrelevant for the subsequent deprotection/cyclization to the pyrroles 57 since this step took place with concomitant E/Z-isomerization. 

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