Highly functionalized alkenes

In the absence of directing groups, the sense of induction in the cyclopropanation of cyclic alkenes is predicted on the basis of the minimization of steric interactions. An intermediate in the synthesis of (+)-acetoxycrenulide was prepared by this key reaction in which the carbenoid attack occurred from the side opposite to the methyl group of this highly functionalized alkene (equation 57) . 

The Heck reaction is well developed as a method for alkylating aromatics. Frank Glorius of the Max-Planck-lnstitute, Mulheim, reports (Tetrahedron Lett. 44 5751,2003) that chloroacetamides and bromoacelonitrile can also be activated by catalytic Pd to give the coupled products. This reaction works well with enol ethers, to give highly functionalized alkenes, but it also works well with a simple cyclic alkene. 

The cross-coupling reaction with non-activated iodoalkenes proceeds well only by using a polar solvent like NMP or DMPU [29] and elevated reaction temperatures (60 °C, 12 h). The compatibility of the zinc-copper reagents with these harsh reaction conditions shows the remarkable thermal stability of zinc-copper organometallics. The cross-coupling reaction occurs with complete retention of the configuration of the double bond and allows the stereospecific synthesis of highly functionalized alkenes like 29 (see Section 9.6.6 Scheme 9-27) [57],... 

Recently, Darses et al. described for the first time a rhodium-catalyzed 1,4-addition of organoboranes to hindered MBH adducts, trisubstituted alkenes, to afford highly functionalized alkenes 483, via addition of organoboranes and p-hydroxy elimination (Scheme 3.213). Moreover, preliminary results showed that enantio-enriched products 484 were easily accessible by using a mono-substituted chiral diene 485 as ligand, while chiral phosphane ligands were completely ineffective. ... 

A selective magnesiation or zincation of highly functionalized alkenes and cycloalkenes using 2,2,6,6-tetramethylpiperidinyl bases has been reported. The kinetically very active tetramethylpiperidinyl bases allow the smooth metalation of various substituted olefins under practical reaction conditions to give unsaturated organometallic compounds. 

Highly functionalized alkenes R CH2CH=C(E)CH(Nu)R have been prepared via the PhjP-catalysed /3 -umpolung addition of nucleophiles, such as ROH, RR NH, CH2(CN)2, RCH(CN)C02Et, and PhSH, to activated a-disubstituted allenes R CH=C=C(E)CH2R (E = C02Et, CN), often with high stereoselectivity. ... 

Non-functionalized alkenes 6, with an isolated carbon-carbon double bond lacking an additional coordination site, can be epoxidized with high enantiomeric excess by applying the Jacobsen-Katsuki epoxidation procedure using optically active manganese(iii) complexes ... 

Hydrozirconation of terminal alkynes R-C=CH (R= aryl, alkyl) with 1 affords terminally ( )-Zr-substituted alkenes with high efficiency and excellent stereochemical and regiochemical control (>98%). These alkenylzirconocene complexes are of particular interest for synthetic use [136, 143, 144]. Moreover, beside the electropositive halogen sources [145] and heteroatom electrophiles [3] used in the pioneering studies to directly cleave the Zr-C bond, ( )-vinyl-Zr complexes were recently transformed into a number of other trans-functionalized alkenes such as ( )-vinyl-sul-fides[146], vinylic selenol esters [147], vinyl-sulfones [148], vinyl-iodonium [149], vinyl-(R0)2P(0) [150], and vinilic tellurides [143]. 

Cyclopentadienylindium(I) has been shown to be effective in the reaction with aldehydes or electron-deficient alkenes to form highly functionalized cyclopentadienes in aqueous media (See Section 8.4.3).101 This reaction with the appropriate substrates can be followed by an intramolecular Diels-Alder reaction in the same pot to provide complex tricyclic structures in a synthetically efficient manner (Scheme 12.4). 

The [5 + 2]-cycloadditions of air-stable 7]3-pyranyl and 7]3-pyridinyl molybdenum 7T-complexes (4758 and 48,59 respectively) with alkenes reported by Liebeskind and co-workers provide a novel method for the construction of oxabicyclo[3.2.1]octenes and highly functionalized tropanes (Scheme 20). This process involves the formation of a TpMo(CO)2 complex which in the presence of EtAlCl2 reacts with an alkene in a stereoselective [5 + 21-cycloaddition to give metal-complexed cycloadducts 50 and 51 (Tp = hydridotrispyrazolylborato). Metal decomplexation via protiodemetalation or oxidation affords the products in good to excellent yields (Scheme 21). 

Unfunctionalized alkenes have posed more of a problem, as they have no polar moiety which can coordinate to the catalyst. Such an additional metal binding site next to the C = C bond has proven to be crucial for directing coordination to the catalyst and, therefore, rhodium and ruthenium complexes, which are highly selective for functionalized alkenes, generally provide only low enan-tioselectivity for this class of substrates. 

The transition metal cross-couplings of allenes described here offer practical solutions for the modification of 1,2-dienes and access to the preparation of highly functionalized 1,3-dienes, alkynes and alkenes, which are often not easily accessible in a regio- and stereoselective manner by classical methods. Some of the prepared alkynes or functionalized allenes serve as important intermediates in syntheses of natural products, biologically active compounds, e.g. enynes and enyne-allenes, and new materials. It can be predicted that further synthetic efforts will surely be focused on new applications of allenes in transition metal-catalyzed cross-coupling reactions. 

The limitations of hydroformylation reactions in water are the same as those of hydrogenation reactions, i.e. the poor solubility of the substrates (see Section 8.2.1). While aqueous-organic biphasic hydroformylation works well for alkenes with chain lengths up to C7, the solubility of longer chain alkenes is too low for viable processes. Although simple alkenes are poorly soluble, many functional alkenes have solubilities in water that are sufficiently high to avoid mass transfer problems, but at the same time this can impede separation. 

The inverse-electron-demand Diels-Alder reaction of 3,6-dichloro[l,2,4,5]tetrazine with alkenes and alkynes provides the synthesis of highly functionalized pyridazines. ° Also, the 4 + 2-cycloaddition reactions of the parent [l,2,4,5]tetrazine with donor-substituted alkynes, alkenes, donor-substituted and unsubstituted cycloalkenes, ketene acetals, and aminals have been investigated. ... 

The cross-metathesis of terminal alkenes and functionalized alkenes is shown in Table 6.2. In each case, a CM product is obtained in high yield and an -isomer is formed predominantly. ... 

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