Z-vinyl iodide

The coupling of alkenylboranes with alkenyl halides is particularly useful for the stereoselective synthesis of conjugated dienes of the four possible double bond isomers[499]. The E and Z forms of vinylboron compounds can be prepared by hydroboration of alkynes and haloalkynes, and their reaction with ( ) or (Z)-vinyl iodides or bromides proceeds without isomerization, and the conjugated dienes of four possible isomeric forms can be prepared in high purity. 

Z-vinyl iodide was obtained by hydroboration and protonolysis of an iodoalkyne. The two major fragments were coupled by a Suzuki reaction at Steps H-l and H-2 between a vinylborane and vinyl iodide to form the C(ll)-C(12) bond. The macrocyclization was done by an aldol addition reaction at Step H-4. The enolate of the C(2) acetate adds to the C(3) aldehyde, creating the C(2)-C(3) bond and also establishing the configuration at C(3). The final steps involve selective deprotonation and oxidation at C(5), deprotection at C(3) and C(7), and epoxidation. 

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. 

Further examples of the formation of carbocyclic and carbopolycyclic compounds from (Z)-vinyl iodides with triethylamine as base have been reported and as noted in the related bromide reactions, double-bond isomerization is commonly observed.92... 

Removal of the tri-wo-propylsilyl (TIPS) and tm-butyldimethylsilyl (TBS) protecting groups could be accomplished concomitantly with TBAF in tetrahydrofuran at 0 °C, but here competing elimination of the secondary bromide was observed. Better overall yields and cleaner conversion was observed when TBS ether was cleaved with 5 % aqueous HF in acetonitrile at 0 °C followed by removal of the acetylenic TIPS with TBAF under milder conditions of -78 °C.10 The diastereomers are not separated before the desilylation process therefore even a 3 1 mixture of E- and Z-enyne is obtained. Prelaureatin 4 and its F-isomer 17 are likewise goals in natural product synthesis. Crimmins and co-workers developed an own synthetic route to 4. The reaction sequence is similar up to aldehyde 55. Afterwards a Z-vinyl-iodide is selectively formed and the alkyne is introduced via a Sonogashira reaction. 

Z)-l-Iodo-l-alkenes. Reaction of sodium hexamethyldisilazane with the phos-phonium salt 1 in THF generates iodomethylenetriphenylphosphorane, (C6H5)3P=CHI, which converts aldehydes into (Z)-vinyl iodides (15-62 1) in reactions conducted at —78° in THF/HMPT in 61-91% yield.2... 

The selective reduction of the 8-hydroxy- 3-keto ester 4 with Me4NBH(OAc)3 afforded the corresponding l,3-anft -diol in 87% yield and 14 1 diastereoselectiv-ity. The 1,3-anti -diol was protected as the acetonide 5, followed by a Pd-catalyzed coupling reaction with the vinyl iodide 6 to provide the diene 7 in 69% yield. Reduction of the ester, Swem oxidation, and finally, Wittig olefination afforded the (Z)-vinyl iodide 8. 

Prclaureatin 4 and its E-isomcr 17 are likewise goals in natural product synthesis. Crimmins and co-workers developed an own synthetic route to 4. The reaction sequence is similar up to aldehyde 55. Afterwards a Z-vinyl-iodide is selectively formed and the allcyiie is introduced via a Sonogashira rcaction. 

Both these reactions are stereoselective. Chloride prefers to add anti to the ketone in the linear vinyl cation intermediate 67. Rotation of the o-bond in the enolate intermediate 69 in the conjugate substitution allows loss of chloride to give either the E- or the Z-vinyl iodide 66. 

A dramatic example of this technique is the last step of Heathcock s synthesis of myxalamide A 96. Hydroboration of the alkyne 94 with catechol borane gives the A-vinyl borane and this is combined with the Z-vinyl iodide 95 in a palladium-catalysed Suzuki coupling to give the natural product 96 with every alkene correct.17... 

Each half of the molecule was made as a single enantiomer by catalytic asymmetric synthesis. We are concerned with the vinyl iodide 203. The obvious reduction of 205 with DIBAL failed and instead hydrotitanation gave the Z-vinyl silane 206. Replacement of Me3Si with iodine was regio-and stereospecific giving only the Z-vinyl iodide in 59% yield. 

Intramolecular coupling of a Z-vinyl iodide and a saturated alkyl chain in 282 creates a new 11-membered ring 283 providing the ansa bridge in Danishefsky s synthesis49 of xestocyclamine A. The yield in the formation of this difficult medium ring and the toleration of functionality are both impressive. 

Both these products were used in the synthesis of epothilone A 173. The disconnection of the lactone is simple but the other is less obvious. The epoxide must come from a cis alkene and that can be made by a Suzuki coupling of a borane derived from 174 and the Z-vinyl iodide 175. As you will see, 174 was made from 169 and 175 from 172, unlikely as it seems. 

Compound 34 was transformed to vinyl iodide 38, which corresponds to the C9-C14 fragment of discodermolide. After protection and reduction (Dibal-H), 34 was transformed to aldehyde 37 which was then converted to the (Z)-vinyl iodide 38 by using the iodoethylphosphonium (EtPPhal) [46]. The overall yield for the preparation for vinyl iodide 38 from 34 is 35% (Scheme 8). 

Brown s conditions afforded 564 with high ee. Acylation, oxidative cleavage of double bond, and Wittig olefination gave (Z)-vinyl iodide 565. 

Oxidation of cyclic enol ether 35 with dimethyl dioxirane (DMDO) followed by in situ reduction of the intermediate epoxide with DIBALH gave secondary alcohol as a 10 1 mixture of diastereom-ers. Oxidation of these alcohols with TPAP/NMO afforded a 10 1 mixture of ketone 37 and its C16 epimer. The isomers were separated and the minor isomer was recycled to a 4 1 mixture of isomers by treatment with imidazole. Subsequent construction of the D-ring was performed by radical reduction of mixed thioacetal in the same way as that adopted by the Sasaki group, leading to octacycle 38. Stereoselective installation of the triene side chain was then carried out via (Z)-vinyl iodide 39... 

Akin to (—)-stipiamide (28) is (-)-myxalamide A (29), the , , Z, , -pentaene portion having been fashioned via the alternative Suzuki process between a vinyl catecholborane (formed in situ via hydroboration of alkyne 33) and Z-vinyl iodide 32 (Scheme 15). Using catalytic Pd(OAc)2 and the water-soluble phosphine ligand TPPTS, coupling in aqueous CH3CN at room temperature gave the desired natural product in 44% isolated yield as a pure isomer. 

In 2002, Lett et al. published a convergent stereospecific synthesis of the resorcylic macolactone LL-Zl 640-2 (567) (Scheme 9.13) and hence hypothemycin (481) 382, 383). They started with the preparation of the three building blocks, 551, 555 (Scheme 9.11), and 564 (Scheme 9.12). Methyl ester 551 was produced from 4-methoxysalicylic acid (549) in four steps. Reaction of alkyne 552 with enantiopure (/ )-propylene oxide 490 afforded chiral alkyne 553, which then was converted into (Z)-vinyl iodide 555. 

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