Cross couphng

Other types of HIV-1 protease inhibitors have also been prepared using microwave-promoted Suzuki reaction [37]. The symmetric cyclic sulfamide (3K,4S,5S,6it)-3,6-bis(phenoxymethyl)-2,7-bis[4-(2-thienyl)benzyl]-l,2,7-thi-adiazepane-4,5-diol 1,1-dioxide, for instance, was synthesized via cross-couphng of (3aS,4R,8it,8aS) - 5,7 - bis(4 - bromobenzyl) - 2,2 - dimethyl - 4,8 - bis-(phenoxymethyl) hexahydro [1,3] dioxolo [4,5 - d] [ 1,2,7 ] - thiadiazepine 6,6 - dioxide with 2-thienylboronic acid for 3 min at 45 W (Scheme 19). 

For example, the sensitive imidoyl chloride moiety at the C-3 position of the pyrazinone scaffold is known to vmdergo Stille reactions with a variety of tetraaryltin reagents, generating the corresponding 3-substituted pyrazi-nones (Scheme 10) [26]. Furthermore, the transition-metal-catalyzed stannyl-ation at the C-3 position is also documented in the hterature, in view of cross-couphng with a variety of alkyl and (hetero)aryl hahdes [26]. However, this strategy is completely restricted to the C-3 position, while the Cl atom of C-5 position was found to be inert under these conditions. 

One of the first cross-coupling reactions performed on solid supports was the Stille reaction [250] which is a paUadium-catalyzed reaction of a trialkylaryl or trialkylalkenyl stannane with an aromatic iodide, bromide or triflate. In contrast to the process in liquid-phase, the organotin reagent is easily removed from the solid-phase because of the subsequent washing processes. Immobilized aryl halides have been frequently coupled with aryl and alkenylstannanes, whereas stan-nanes attached to the solid support have been used less frequently for the StiUe reaction. An example is the synthesis of a benzodiazepine library by EUman et al. Recently, a Stille cross-couphng reaction has been employed in the synthesis of al-kenyldiarylmethanes (ADAM) series of non-nucleoside HlV-1 Reverse Transcriptase Inhibitors (Scheme 3.14) [251]. 

Transformations on this support included the synthesis of aminoketones from supported chloroketones as weU as biarylaldehydes after Suzuki cross-couphng reactions of supported bromo-benzaldehydes [21]. This dendritic polyglycerol was... 

Recent trend in the synthesis of olefinic pheromones is the use of transition metal-catalyzed cross couphng reaction for carbon-carbon bond formation. Scheme 8 summarizes a synthesis of the termite trail marker pheromone, (3Z,6Z)-3,6-dodecadien-l-ol (2) by Oehlschlager [19]. The key-step is the palladium-catalyzed cross-couphng of allyhc chloride A and alkenylalane B. 

When nitroalkenes were used as Michael acceptors, high yields and enantioselectivities of the desired Michael addition products were also obtained (Scheme 5.22). In these reactions, a well-defined chiral Ru amido complex (Figure 5.9) was an efficient catalyst. The mild reaction conditions and high reactivities and stereoselectivities allowed a large-scale reaction in the presence 1 mol% Ru catalyst. By using a chiral Pd(II) catalyst, an asymmetric allylic arylation was reported by Mikami and coworkers to give the cross-couphng product via the activation of both allylic C H and aryl C H bonds in moderate enantioselectivity (Scheme 5.23). ... 

The stereospecific rhodium-catalyzed allyhc hnchpin cross-couphng reaction provides an expeditious route to stereotetrads (Scheme 10.5). This study demonstrated that improved stereospecificity could be obtained at lower temperature for the formation of the alkylation product 18 (2° 1°=24 1 ds=26 l compare Tab. 10.2, entry 1). Krapcho... 

Knochel et al. described Pd-catalyzed Negishi cross-coupHng reactions between zinc organometallics and aryl iodides in [BMMIM][BF4j. Scheme 5.2-20 illustrates the reachon for the formahon of a 3-subsfituted cyclohexenone from 3-iodo-2-cyclo-hexen-l-one [82]. 

SCHEME 85. Cross-couphng of zinc-copper organometallics with 1-haloalkynes... 

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