Vinylogous stereoselectivity

The Michael reaction is of central importance here. This reaction is a vinylogous aldol addition, and most facts, which have been discussed in section 1.10, also apply here the reaction is catalyzed by acids and by bases, and it may be made regioselective by the choice of appropriate enol derivatives. Stereoselectivity is also observed in reactions with cyclic educts. An important difference to the aldol addition is, that the Michael addition is usually less prone to sterical hindrance. This is evidenced by the two examples given below, in which cyclic 1,3-diketones add to o, -unsaturated carbonyl compounds (K. Hiroi, 1975 H, Smith, 1964). 

Triisopropylsilyloxyfurans were effective nucleophiles for the vinylogous Mannich addition to iminium ions that were formed by Rh2(cap)4-catalyzed oxidation of N-alkyl groups by THYDRO <06JA5648>. A stereoselective addition of 2-trimethylsilyloxyfurans to aryl aldehydes-derived aldimines employing a chiral phosphine/Ag complex as catalyst was developed <06AG(I)7230>. The prototypical example is shown below. 

The reaction of a-halosulphonc with a base to give an olefin is known as Ramberg-Backlund reaction52. A vinylogous version of this rearrangement results in the formation of 1,3-dienes (equation 21)53. Another variation of this reaction is shown in equation 2254. These rearrangements proceed with moderate stereoselectivity. 

The base-catalysed ring contraction of 1,3-dioxepanes offers an attractive route to 4-formyl tetrahydropyrans (Scheme 14) , whilst fused exo-cyclic dienes 27 result from the radical cyclisation of alkenyl iodides 26 (Scheme 15) <00OL2011>. Intramolecular radical addition to vinylogous sulfonates is highly stereoselective, leading to the ci s-2,6-disubstituted tetrahydropyran (Scheme 16) . 

A third mechanistically distinct [3 -1- 2] cycloaddition between vinyl ethers and vinyl-carbenoids was discovered and reported in 2001 [26]. This reaction is remarkable because when Rh2(S-DOSP)4 is used as the catalyst, the cis-cyclopentenes 142 are formed in up to 99% enantiomeric excess. The reaction occurs between vinylcarbenoids unsubstituted or alkyl-substituted at the vinyl terminus and vinyl ethers substituted with an aryl or vinyl group. Some illustrative examples are shown in Tab. 14.12. The reaction is considered to be a concerted process, which would be consistent with the highly stereoselective nature of the reaction [26]. Contrary to the [3-1-2] cycloaddition derived by means of vinylogous carbenoid reactivity, this latest [3 -1- 2] cycloaddition is not influenced by solvent effects. Due to steric demands on the carbenoid, the [3-1-2] cycloaddi-tion only occurs with cis-vinyl ethers. 

Stereochemical investigation on the vinylogous 1,5-elimination reactions of 16 to give cyclopropylalkenes has revealed highswi stereoselectively of the intramolecular SN process (equation 18)30. The stereoselectivity of the cyclization reaction of 17 to give the ( )-isomer is improved by the increase in steric bulkiness of the sulfonyl substituent (equation 19)31. 

Scheme 32 illustrates an application of a 6-exo-trig radical cyclization in the total synthesis of ( )-mossambine (166) [68-69]. Indoloazepine 160 was obtained from tiyptamine in four steps (30% overall yield). Pyrolysis of 160 in refluxing toluene in the presence of 2-acetoxyacetaldehyde led to transient generation of an enamine acrylate 161, which stereoselectively formed the tetracyclic vinylogous urethane 162. Hydrolysis of the acetate... 

Alternatively, direct reduction of 169 with LiAlH4 proceeded via stereoselective 1,4-addition to give a mixture (about 3 1) of ( )-a-dihydrocaranone (170) together with ( )-l-epi-y-dihydrocaranine (171). While the cyclization of 167 to 168 may also be effected by preparative electrochemical oxidation at +1.50 V (SCE) in fair yield, the application of this technique to the vinylogous... 

A highly stereoselective vinylogous Pummerer rearrangement of a optically active sulfoxide has been shown to proceed by a [l,4]-migration of the sulfinyl oxygen atom via an intermediate intimate ion pair (Scheme 12).16 The reaction occurs with high enantioselectivity when o-sulfinyl-substituted benzyl carbanions are treated with trimethylsilyl halides. 

After mercury(II)-assisted hydrolysis of the thioenol ether, aldehyde 3 was obtained. This was then subjected to the critical vinylogous aldol reaction needed to complete the carbon backbone of the natural product. The latter process furnished a 3.5 1 mixture of the y to ot addition products. The stereoselectivity observed in the installation of the C(5)-hydroxyl (natural product numbering) was only 2 1. Fortunately, the predominant isomer was the desired product 2. In retrospect, it can be seen that the level of selectivity attained conformed to the predictions of the Still model.4... 

Y. Yamamoto, Formation of C-C Bonds by Reactions Involving Olefinic Double Bonds, Vinylogous Substitution Reactions, in Methoden Org. Chem. (Houben-Weyl) 4th ed. 1952-, Stereoselective Synthesis (G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann, Eds.), Vol. E21b, 2011, Georg Thieme Verlag, Stuttgart, 1995. 

The stereoselectivity of the reduction of vinylogous urethane 4, as shown in Scheme 2, may be attributed to steric hindrance, by which the catalytic hydrogenation occurs from the less hindered site (a-face) of 4 to give an all cw-substituted reduction product (Fig 2). 

A highly stereoselective synthesis of ( )-gephyrotoxin (20) has been carried out. An interesting feature is the reversal of the stereochemical course of the hydrogenation of the vinylogous amide (21) by the use of an alumina support. Hydrogenation of (21) over palladium on charcoal gives the amino-alcohol (22) as... 

Among terpenoid substrates bearing the alkyl ketone moiety, 4-caranone" and 2-pincne-4-one," in addition to camphor, are worth mentioning. The stereoselectivity of aminomethylation" is remarkably affected by the reaction conditions moreover, the tendency of 2-pinene-4-one, like steroid substrates, to give the vinylogous Mannich base (Table 8, Chap. I, C. 1) is important. 

Vinylogous modes of this rearrangement are also possible. Complex systems can be attained by utilizing a built-in electrophile in an intramolecular ring expansion/alkylation, as shown in equation (35). This kind of cyclization is applicable to seven- and eight-membered carbocyclic ring synthesis and proceeds with approximately 12 1 stereoselectivity, which is due to the more stable, parallel conformation depicted in equation (35). ... 

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