Acyclic systems addition

The intramolecular Michael addition of acyclic systems is often hampered by competing reactions, i.e., aldol condensations. With the proper choice of Michael donor and acceptor, the intramolecular addition provides a route to tram-substituted cyclopentanones, and cyclopentane and cyclohexane derivatives. Representative examples are the cyclizations of /3-oxo ester substituted enones and a,/J-unsaturated esters. 

Oxygen-17 NMR spectroscopy has an immense potential for structural analysis of cyclic sulfoxides and sulfones as well as for providing insight into the nature of bonding within these two functional groups . Indeed, in addition to data concerning the NMR chemical shifts for several cyclic sulfoxides and sulfones, NMR chemical shift differences between several diastereotopic sulfonyl oxygens in both cyclic and acyclic systems have been reported . 

The first example of an intermolecular radical addihon/intermolecular trapping domino reactions of an acyclic system in a stereocontrolled fashion to build stereo-genic centers at the a- and 3-carbons was described by Sibi and coworkers [59]. Enantioselective addition of in-sitw-prepared alkyl radical to crotonate or cinnamate,... 

Thermolysis of the syn and anti /J-acetoxy stannanes, obtained by addition of Bu3SnLi to tram- or cis- 1,2-dimethyloxirane and subsequent acetylation, led to (Z)- or (E)-2-butene, respectively, by a stereospecific anti process (equation 34).73. It is postulated that a hyperconjugative interaction of the C—Sn bond facilitates departure of the acetate group in these acyclic systems. The trimethylstannyl and triphenylstannyl analogues likewise undergo anti elimination. 

In addition to being treated in a similar manner to acyclic systems, cyclic systems can also be disconnected according to concerted pericyclic or cheletropic cycloreversions. In this context, the Woodward-Hoffmann rules [2] are of... 

Use of TMSCl in combination with HMPA, DMAP, or TMEDA all favored 1,2-addition over 1,4-addition. Sequential a-alkoxyalkylcuprate conjugate addition, enolate trapping with TMSCl, and silyl enol ether alkylation provides a one-pot synthesis of tetrahydrofurans (Scheme 3.35) [129]. Cyclic enones afford as-fused tetrahydrofurans, while acyclic systems give complex mixtures of diastereomers. a-Alkoxyalkylcopper reagents also participate in allylic substitution reactions with ammonium salts [127]. 

This isomerization was used in the heteroconjugate addition to the acyclic system. Therefore, the substituted olefin 72, in which the double bond is conjugated with both sulfone and silicon atoms, undergoes a diastereoselective addition of CHsLi. The resulting lithium alcoholate is quantitatively converted into the silyl ether dianion 73 and the addition of deuterium oxide afforded the functionalized product 74 in excellent yield (equation 16. 

Of course, one can use estimates (34)-(37) to obtain a similar perturbation analysis for more general acyclic systems (instead of a linear chain). If we add a reaction to an acyclic system (after that a cycle may appear) and assume that the reaction rate constant for additional reaction is smaller than all other reaction constants, then the generalization is easy. 

This smallness with respect to all constants is required only in a very special case when the additional reaction has a form A, Aj (with the rate constant fc, ) and there is no reaction of the form A,. .. in the nonperturbed system. In Section 7 and Appendix 1 we demonstrated that if in a nonperturbed acyclic system there exists another reaction of the form A,. .. with rate constant k,-, then we need inequality fcy, k, only. This inequality allows us to get the uniform estimates of eigenvectors for all possible values of other rate constants (under the diagonally gap condition in the nonperturbed system). 

The same SN2 addition is also observed in reactions of the cuprate with the silyl enol ether or the enol phosphate of the epoxy ketone. This regiosclectivity is applicable to five- and six-membered ring systems and, to a lesser extent, to acyclic systems, which are generally less reactive. 

Thus changing the ligands on dirhodium(II) can provide a switch which, in some cases, can turn competitive transformations on or ofF. Other examples include the use of dirhodium(II) carboxamides to promote cyclopropanation and suppress aromatic cyclo-addition. For example, catalytic decomposition of diazoketone 105 with dirhodium(II) caprolactamate [Rh2(cap)4] provides only cyclopropanation product 106. In contrast, dirhodium(II) perfluorobutyrate [Rh2(pfb)4] or dirhodium(II)triphenylacetate [Rh2(tpa)4] gave the aromatic cycloaddition product 107 exclusively (equation 100) Although we have already seen that rhodium(II) acetate catalysed decomposition of diazoketone 59, which bears both aromatic and olefinic functionalities, afforded stable norcaradiene 60 (equation 70) ° the rhodium(II) acetate catalysed carbenoid transformation within an acyclic system (108) showed no chemoselectivity (equation 101). However, when dirhodi-um(II) carboxamides were employed as catalysts for this tvpe of transformation, only cyclopropanation product 109 was obtained (equation lOl) ". ... 

Conjugate additions. The silyl cuprate rcapcnt (PhMc,Si),CuLi (1) undergoes conjugate addition to a,(3-unsaturated aldehydes, ketones, or esters to form (3-silyl carbonyl compounds. Methylation of the intermediate enolate in acyclic systems is highly dia-stereoselective in favor of the isomer in which the silyl and methyl groups have the anti-... 

Ligands such as phosphoramidite (3) and TADDOLs (4) have proven to be remarkably discriminating in their reactions of cyclic cases. Due to interconversion between s-cis and s-trans conformers, acyclic systems have been far more challenging. Here, optically pure peptidic phosphines (e.g. 5) deliver products of 1,4-additions in good yields and high enantioselectivities (equation 9). 

One of the few examples of an intramolecular carbene addition to an imino-bond is shown in Scheme 6 <19990L667>. Isoquinoline diazoamide 35 was subjected to standard dirhodium catalysis. The resulting aziridino-isoquinoline 36 was isolated in an excellent 87% yield. The N-O invertomers could be isolated chromatographically. Several other cyclic and acyclic systems were also synthesized. A simple acyclic system provided an 86% yield of a bisazabicyclo[3.1.0]hexane system. A pyrrolizidine aziridine was prepared in 60% overall yield. 

In addition to cyclic allylic substrates, malonate nucleophiles have been used in reactions with both symmetrical" and unsymmetrical" acyclic systems, and with geminal dicarboxylates. Malonates and Meldrum s acid have also been used as nucleophiles in the desymmetrization of meso diesters. 

Nucleophilic additions to cyclic carbonyl compounds differ greatly from those of acyclic systems. In acyclic systems, only the configuration at an adjacent (1,2-asymmetric induction) or nea y center (remote asymmetric induction) is usually considered in predicting the outcome of nucleophilic attack. In cyclic systems, the conformation of the entire molecule (which is in part determined by the individual substituents) must be considered when predicting the mode of nucleophilic attack. Furthermore, a number of other factors such as torsional and electronic effects also play a role in the stereochemical course of additions to cyclic substrates. The relative importance of all of these effects (as well as others) has been the subject of considerable debate in the literature, and has not as yet been adequately resolved. ... 

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