A new variant of the tandem inter [4 + 2]/intra [3 + 2] cycloaddition of nitroalkenes is described in detail. The scope and limitations of the bridged mode tandem cycloaddition in which the diene and dienophile are part of the same molecule are documented. Simple 1,4-pentadienes as well as 2-alkoxy-1,4-pentadienes can function effectively as dienophile and dipolarophile combinations with excellent chemical selectivity and regio- and diastereoselectivities. Hydrogenation of the bridged nitroso acetals produces aminocyclohexanemethanol derivatives in high diastereo- and enantioselectivities. Further, insights into the mechanistic aspects of the Raney nickel promoted hydrogenation are reported. An intriguing influence of the nitro olefin α-substituent on the diastereoselectivity in the [4 + 2] cycloaddition has been documented. The reactivity of the α-chloro-substituted nitroalkene 26 as the heterodiene in the Diels−Alder reaction is assayed, and the use of the chlorine atom as a hydrogen surrogate is described.

Recently, efforts to identify biologically important natural products from cyanobacteria resulted in the isolation of several welwitindolinone alkaloids, two of which have been identified as antagonists of the P-glycoprotein P-170 and hence as MDRreversing agents. 1 As part of an ongoing synthesis directed toward the most potent congener, N-methylwelwitindolinone C isothiocyanate (1), we developed an efficient synthesis of 3, a key intermediate that contains the complete carbon framework. Herein we report the details of our investigation.From a retrosynthetic perspective we are focusing on a strategy wherein the chloroolefin and sensitive isothiocyanate will arise late in the sequence via interchange of a ketone and hydroxyl moiety, respectively, in intermediate 2 (Scheme 1). To access 2 the approach proceeds through 3 and, in turn, two R-diazo ketones, 4 and 5. The more advanced of these, compound 4, is a versatile intermediate from which several end-game scenarios are being explored. The second, diazo ketone 5, serves as precursor to 4 and enables the use of aryl C-H insertion chemistry in assembling the 3,4-bridged oxindole core from isatin (6).In the forward sense, isatin was found to be an excellent substrate for Wittig homologation with ethyl triphenylphosphoranylidene acetate. 2 The derived enoate ( 7) is produced in high yield and complete selectivity for the illustrated olefin isomer (Scheme 2). Sequential exposure of 7 to isopropyl triphenylphoshorane and MeI results in clean conversion to the corresponding gem-dimethyl cyclopropane 8. 3 Saponification of 8 furnishes acid 9 which, 4 upon conversion to its acid chloride and treatment with diazomethane produces R-diazo ketone 5.Having established ready access to diazo ketone 5, efforts to prepare 15 via aryl C-H insertion began. 5 Initial studies illustrated that if Rh 2 (TFA) 4 is used as catalyst, 5 reacts to produce equimolar amounts of 14 and 15 along with a trace of spirocycle 11. After considerable experimentation it was discovered that the norcaradiene/cycloheptatriene interconversion leading to the undesired byproduct 14 (i.e., 13 f 12) can be suppressed in situ with the mildly Lewis acidic clay, Montmorillonite K10. 6 Under these 10.

Nuclear spin—lattice relaxation times have been measured as a function of temperature for a number of liquid hydrocarbons. These data, together with other available measurements on rigid, spheroidal molecules, are compared with the Bloembergen, Purcell, and Pound (B.P.P.) theory of spin—lattice relaxation in liquids, and it is shown that the B.P.P. calculation of the rotational contribution to the relaxation time gives a value which are much shorter than the total experimental relaxation times. It is then assumed that the time dependence of the rotational angular autocorrelation functions of these molecules is dominated by dynamical coherence, rather than by frictional forces as assumed in the B.P.P. theory. If one calculates the net spin—lattice relaxation time T1 by summing the translational contribution calculated from the B.P.P. theory and the rotational contribution calculated from an approximate autocorrelation function valid for small but nonzero friction constants, one obtains values for T1 which are in quantitative agreement with the data for nonpolar, spheroidal molecules. Furthermore, when the two calculations are compared with the data for polar spheroidal molecules, it is seen that frictional forces are the predominant factor in the rotational motion of these systems, but the values obtained for the rotational friction constant from the Stokes—Einstein equation are in error by a considerable amount.

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An asymmetric, tandem inter [4 + 2]/intra [3 + 2] bridged mode (beta-tether) cycloaddition of nitroalkenes has been developed. This new sequence involves the Lewis acid-promoted [4 + 2] cycloaddition of nitro olefins with enantiopure 1-alkoxy-1,4-dienes. The resulting nitronates, bearing a C(5) tethered dipolarophile, undergo thermal, intramolecular [3 + 2] cycloaddition to afford stable tricyclic nitroso acetals, which can be subsequently reduced to provide interesting aminocyclopentanes. Thus, in three steps, highly functionalized, enantiomerically enriched aminocyclopentanes can be constructed with good yield and high ee. Additionally, the Lewis acid was found to impart a remarkable influence on the stereochemical outcome of the [4 + 2] cycloaddition.