Stereospecific cross-coupling reactions

The utility of the Suzuki reaction in the challenging arena of natural product total synthesis has been explored. The constitution of bombykol (106) (see Scheme 26), a well-known pheromone, lends itself to a Suzuki coupling. Indeed, in a short stereospecific synthesis of 106, Suginome et al. demonstrated that ( )-vinylboronic acid ( )-104 can be smoothly cross-coupled with (Z)-l-pentenyl bromide [(Z)-105] 44 the configurations of both coupling partners are preserved in the C-C bond forming process. 

The involvement of organocopper intermediates in various cross-coupling reactions carried out in the presence of Cu1 is often suggested, although in the majority of cases no experimental proof is provided, and the actual role of Cu1 may be different (Section 9.6.3.2.1). The potential of copper-mediated cross-coupling can be shown by the stereospecific reaction of 3-trimethylsilylallylic alcohols, which takes place via a prior transmetalation of Si to Cu (37).157... 

Vinylic halides or vinyl-metal species couple with a very high degree of stereospecificity, cry-vinylic halides giving cis coupling products and tra/iy-vinylic halides trans coupling products (example 17, Table III). Aromatic halides give homo- or cross-coupling reactions (examples 18 and 19, Table III). 

The sequential approach is also common in proposals written by synthetic chemists (a multistep synthesis is inherently step by step). Vyvyan (excerpt 13N), for example, proposes a strategy to synthesize a select group of heliannuols (alleo-pathic natural products isolated from the sunflower) in an optically pure form. One approach that he will explore involves enantioselective cross-coupling reactions between an alkyl zinc reagent and an aryl bromide. He begins with experiments that will utilize recently developed catalysts and produce products with known optical rotation data. Subsequent reactions are described that will lead potentially to the desired stereospecific heliannuols A and D. 

Scheme 10.5 The stereospecific allylic substitution approach to a stereotetrad using a linchpin cross-coupling reaction.

A synthesis of the monomeric unit 128 of a peptide nucleic acid analog (PNA) offers an example of stereospecific cross-coupling of a Reformatsky reagent with (Z)-vinylic iodide 126. The coupling reaction of the preformed Reformatsky reagent prepared in dimethoxymethane (methylal) with 126 is carried out using 8% of Pd(PPh3)4 in DMPU as the solvent at 65 °C to afford 127 (equation 70)161. 

Scheme 5.1 Stereospecific iron-catalyzed cross-coupling reaction reported by Kochi and Tamura in 1971.

Regiospecific generation of vinyl triflate 77 from ketones such as 53 and 54 was planned for the introduction of C-4 substituents via palla-dium(0)-catalyzed cross-coupling reactions to give dehydropyrrolidine enamide derivatives 78 which could be reduced stereospecifically to protected kainoid derivatives 79 (Scheme 33). 

The reaction of tri- -butylindium with tetrachloroethylene affords 3-methyl- 1,1,2-trichloro-l-pentene and indium trichloride without the use of any catalyst and solvent. Other trialkylindium gives similar results (Table 29). The yield of the product based on the amount of trialkylindium used reaches 287%. This fact shows that all three alkyl groups attached to indium are effectively transferred to the product. Several haloalkenes lead to the selective formation of cross-coupling products under similar conditions. A stereospecific cross-coupling with ( )-/3-bromostyrene gives ( )-/ - -butylstyrene. In contrast, starting from both (E)- and (Z)-l,2-dichloroethylene, a mixture of (E)- and (Z)-l-chloro-3-methyl-l-pentene has been obtained in a ratio of 6 4.398... 

The palladium-catalysed cross-coupling of aryl halides or vinyl halides with dialkyl phosphonates (31) to yield dialkyl arylphosphonates and dialkyl vinylphosphonates, respectively, was first reported by Hirao and co-workers 69 the halides used most frequently are bromides and the reaction is stereospecific with haloalkenes. Subsequently, analogous reactions of alkyl alkylphosphinates (32), alkyl arylphosphinates (32), alkyl phosphinates (33), and secondary phosphine oxides (34), replacing [P—H] bonds with [P—C] bonds to yield various phosphinates and tertiary phosphine oxides, have been developed (Figure 7.1). Alkyl phosphinates (33) may be mono- or diarylated as desired by the selection of appropriate conditions. Aiyl and vinyl triflates have also found limited... 

The Mechanism of the cross coupling reaction can be accommodated by an oxidative addition of 1-bromopropene to iron(l) followed by exchange with ethylmagnesium bromide and reductive elimination. Scheme 3 is intended to form a basis for discussion and further study of the catalytic mechanism. In order to maintain the stereospecificity, the oxidative addition of bromo-propene in step a should occur with retention. Similar stereochemistry has been observed in oxidative additions of platinum(O) and nickel(O) complexes.(32)(33) The metathesis of the iron(lll) intermediate in step b is ixp icted to be rapid in analogy with other alkylations.(34) The formation of a new carbon-carbon bond by the redilcTive elimination of a pair of carbon-centered ligands in step c has been demonstrated to occur... 

Finally, the mechanism in Scheme 3 bears a resemblance to that presented above for the nickel-catalyzed reaction of methylmagnesium bromide and aryl bromides. However, there are outstanding differences between iron and nickel in their abilities to effect cross coupling reactions. Iron is a catalyst which is effective at lower temperatures and concentrations than used with nickel. Even more importantly, cross coupling can be effected completely stereospecifically with an iron catalyst and no alkyl isomerization of the Grignard component has been observed, in contrast to the nickel-catalyzed reactions. 

Stereospecific synthesis of alkenes. This Pd(0) complex is an efficient catalyst for the cross-coupling of vinylic halides with a variety of Grignard reagents. The resulting alkenes are obtained in 97% isomeric purity and in yields of 75-90%. This reaction is particularly useful for preparation of pure 1,3-dienes (equation I). ... 

The cross-coupling reaction of (2)- and ( )-vinyl bromides with terminal acetylenes is stereospecific. For example, (Z)-methyl 3-bromoacrylate 127 reacts with 1-hexyne in the presence of a Pd catalyst to form the (Z)-enyne as the only product [Eq. (42)] [63]. 

As discussed above, the cross-coupling reaction of organosilicon compounds proceeds stereospecifically, depending on the reaction conditions. Thus, the transformation C—Si C —C is demonstrated to be accompanied by chirality transfer. Now, the question arises of how to prepare organosilicon compounds whose chiral allylic carbon is substituted by a silyl group. The most accessible solution is asymmetric hydrosilylation of olefins [35]. We studied asymmetric hydrosilylation of 1-substituted 1,3-butadienes using... 

The interesting stereospecific Pd-catalyzed cross-coupling reactions of 1-alkynylzinc chlorides 25 with a diastereoisomeric mixture of alkenyl halides E) or (Z)- 24, have been described. The ( )-bromoalkene reacts preferentially in these reactions to afford good yields of ( )-enynes 26 of very high stereoisomeric purity [Eq. (10)] [18], The enyne can easily be selectively transformed into the corresponding dienes, which may be used to prepare stereodefined polyunsaturated natural products. 

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],... 

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