Methylene cyclohexanes, and

Structurally novel /3-lactams were obtained using enantiopure 4-oxoazetidine-2-carbaldehydes and methylene cyclohexane and a-methyl styrene (Equation (4)).7 Boron trifluoride diethyletherate and tin(iv) chloride produced the products in the highest yields, and all ene products possessed yy/z-stereochemistry. 

An enantioselective imino-ene reaction was developed by Lectka to provide ct-amino acid derivatives.27 Aryl alkenes (cr-methyl styrene, tetralene), aliphatic alkenes (methylene cyclohexane), and heteroatom-containing enes, all gave high yields and high ee s of the homoallylic amides (Equation (17)). The mechanism of this reaction has been proposed to proceed through a concerted pathway. This mechanism is evidenced by a large kinetic isotope effect observed in the transfer of H(D). 

To explore the mechanism of allylic hydroxylation, three probe substrates, 3,3,6,6-tetradeuterocyclohexene, methylene cyclohexane, and /l-pinenc, were studied (113). Each substrate yielded a mixture of two allylic alcohols formed as a consequence of either retention or rearrangement of the double bond. The observation of a significant deuterium isotope effect (4-5) in the oxidation of 3,3,6,6-tetradeuterocyclohexene together with the formation of a mixture of un-rearranged and rearranged allylic alcohols from all three substrates is most consistent with a hydrogen abstraction-oxygen rebound mechanism (Fig. 4.48). 

Cyclohexanol annelation,8 In the presence of dimethylaluminum chloride, a,/3-unsaturated aldehydes or ketones undergo two consecutive ene reactions with alkylidenecycloalkanes to form bicyclic alcohols. Thus, if the reaction of methylene-cyclohexane and methyl vinyl ketone is conducted at — 20°, the product (I) of the initial ene reaction can be isolated in 39% yield together with traces of 2, which becomes the main product from reactions conducted at 25°. The intermediate is usually not isolable in reactions of a,/l-enals. Thus, reaction of ethylidenecyclopentane and acrolein at 0° gives 3 in 72% yield. An attractive feature of this annelation is that... 

A new method for the preparation of thiirans from alkenes employs suc-cinimide- or phthalimide-N-sulphenyl chlorides to form addition compounds, e.g. (320 n = 1, 2, or 4), which, on treatment with LiAlH4 at -78 °C, give the corresponding cycloalkene sulphides (58—97%).The method has also been successfully applied to the preparation of thiirans from styrene, methylene-cyclohexane, and norbornene. 

For methylene cyclohexanes and C-X o-acceptors (Figure 6.86), the dominant interaction pattern is reminiscent of the anomeric effect. Experimental NMR conformational measurements and detailed dissection of NBO interactions in these systems has been provided by Tormena and coworkers. The 1,3 allylic strain can serve as an additional destabilizing effect that disfavors equatorial conformers for substituted alkenes. 

It is thus anticipated that the small-molecule breakdown products will be l,4-bis(methylene)cyclohexane and 4-methylenecyclohex-anemethanol. Such by-products have been found in the pyrolysis of the copolymer poly(ethylene- o-l,4-cyclohexylenedimethylene terephthalate) [87]. 

Two moles of Tebbe s reagent should convert the ketone first to methylene cyclohexane and via that intermediate to product. 

Disubstituted Alkenes are the most reactive class of alkenes in Mc2AlQ catalyzed ene reactions with aldehydes. Good to excellent yields of ene adducts are obtained from methylene-cyclohexane and acetaldehyde, isovaleraldehyde, pivaldehyde or benzaldehyde as well as formaldehyde (as trioxane or paraformaldehyde). 5 Since methylenecyclohexane is easily isomer-... 

A reaction that introduces a second chirality center into a starting material that already has one need not produce equal quantities of two possible diastereomers Con sider catalytic hydrogenation of 2 methyl(methylene)cyclohexane As you might expect both CIS and trans 1 2 dimethylcyclohexane are formed... 

The relative amounts of the two products however are not equal more as 1 2 dimethyl cyclohexane is formed than trans The reason for this is that it is the less hindered face of the double bond that approaches the catalyst surface and is the face to which hydro gen IS transferred Hydrogenation of 2 methyl(methylene)cyclohexane occurs preferen tially at the side of the double bond opposite that of the methyl group and leads to a faster rate of formation of the cis stereoisomer of the product... 

Cyclohexanone shows most of the typical reactions of aUphatic ketones. It reacts with hydroxjiamine, phenyUiydrazine, semicarbazide, Grignard reagents, hydrogen cyanide, sodium bisulfite, etc, to form the usual addition products, and it undergoes the various condensation reactions that are typical of ketones having cx-methylene groups. Reduction converts cyclohexanone to cyclohexanol or cyclohexane, and oxidation with nitric acid converts cyclohexanone almost quantitatively to adipic acid. 

The (TMS)3SiH mediated addition of phosphorus-centered radicals to a number of alkenes has been investigated in some detail. Reaction (73) is an example of phosphorous-carbon bond formation using four structurally different phenylseleno derivatives with 3 equiv of (TMSlsSiH and AIBN in refluxing benzene for 2h. Comparative studies on the reaction of the four phosphorus-centered radicals have been obtained. Although the reaction with 1-methylene cyclohexane is efficient with all four derivatives, different selectivity is observed with electron-rich or electron-poor alkenes. 

Klein showed that axial reaction of the parent methylenecyclohexane 37 is preferred in hydroboration [106], The experimental data on the parent methylenecyclohexanone 37a accumulated by Senda et al. [107] and the more recent systematic studies by Cieplak et al. [108, 109] on jr-facial selectivities of 3-substituted methylene-cyclohexanes 37 have characterized the intrinsic features of the facial selection of methylenecyclohexanes. That is, axial preference of unsubstituted and 3-substituted methylenecyclohexanes was observed in oxymercuration [107] and epoxidation reactions [110], There is also an increase in the proportion of axial attack with increase in the electronegativity of the remote 3-equatorial... 

Chiral bisoxazolines (box) ligands have been attached to a polyethylene glycol (PEG) matrix 25.24 The supported ligands were tested on a variety of reactions for their enantioselectivity. The carbonyl-ene reaction between a-methyl styrene or methylene cyclohexane (26, Equation (15)) and ethylglyoxalate 12 afforded the corresponding ene adduct 27 in 96% and 91% yield and 95% and 85% ee, respectively. 

Trimethylsilyloxy)methylene]cyclohexane was prepared from the corresponding carboxaldehyde according to the method of House.4a b Cyclohexane carboxaldehyde was obtained from the Aldrich Chemical Company, Inc., and purified by distillation at atmospheric pressure (bp 160-164°C). 

A different stereochemical pattern is evident in the hydrogenation over a platinum catalyst of 2-, 3-, or 4-alkyl-substituted methylene-cyclohexanes (57,63,64). With these compounds increasing, the pressure of hydrogen decreases the proportion of the more unstable saturated isomer in the product (cis-1,2-, tmn -l,3-, or cis-l,4-dialkylcyclohexane), a result which is not consistent with a mechanism involving an isomerization to an olefin which yields a proportion of cis and trans isomers different from that given by the methylenecyclohexane. For such a mechanism implies that the hypothetical olefin would yield a larger portion of the more unstable saturated isomer than is obtained from the initial reactant. 

The origin of stereofacial selectivity in electrophilic additions to methylene-cyclohexanes (2) and 5-methylene-l,3-dioxane (3) has been elucidated experimentally (Table 2) and theoretically. Ab initio calculations suggest that two electronic factors contribute to the experimentally observed axial stereoselectivity for polarizable electrophiles (in epoxidation and diimide reduction) the spatial anisotropy of the HOMO (common to both molecules) and the anisotropy in the electrostatic potential field (in the case of methylenedioxane). The anisotropy of the HOMO arises from the important topological difference between the contributions made to the HOMO by the periplanar p C-H a-bonds and opposing p C—O or C—C cr-bonds. In contrast, catalytic reduction proceeds with equatorial face selectivity for both the cyclohexane and the dioxane systems and appears to be governed largely by steric effects. ... 

Among the electron-rich alkenes, vinylsulfides are especially amenable to cation-radical reduction an important feature is the absence of hydrogenolysis of carbon-sulfur bonds. The reduction of [(phenylthio)methylene]cyclohexane is efficient (88%), and the retention of the phenylthio group clearly contrasts with catalytic hydrogenation (Mirafzal et al. 1993). This provides versatile functionality for further synthetic operations. 

Eudragit RS 100, RSPM, S 100 and L 100 were received by courtesy of Rohm Pharma GmbH, Darmstadt, FRG. Theophylline (Indian Pharmacopoeia), polyisobutadiene, acetone, trichloroethylene, cyclohexane and methylene chloride were procured commercially. 

Methylene chloride as solvent for diazomethane etherifications, 41, 9 Methylene cyclohexane, 40, 66 Methylene iodide, reaction with zinc-copper couple and cyclohexene, 41, 73... 

Organometallic methods, with the possible exception of those involving the stoichiometric generation of enolates and other stabilized carbanionic species 140], have seldom been used in carbohydrate chemistry for the synthesis of cyclohexane and cyclopentane derivatives. The present discussion will not cover these areas. The earliest of the examples using a catalytic transition metal appears in the work of Trost and Runge [41], who reported the Pd-catalyzed transformation of the mannose-derived intermediate 22 to the functionalized cyclopentane 23 in 98% yield (Scheme 10). Under a different set of conditions, the same substrate gives a cycloheptenone 24. Other related reactions are the catalytic versions of the Ferrier protocol for the conversion of methylene sugars to cyclohexanones (see Chap. 26) [40,42,43]. 

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