Vinyl iodide oxidation

A plausible mechanism accounting for the catalytic role of nickel(n) chloride has been advanced (see Scheme 4).10 The process may be initiated by reduction of nickel(n) chloride to nickel(o) by two equivalents of chromium(n) chloride, followed by oxidative addition of the vinyl iodide (or related substrate) to give a vinyl nickel(n) reagent. The latter species may then undergo transmetala-tion with a chromium(m) salt leading to a vinyl chromium(m) reagent which then reacts with the aldehyde. The nickel(n) produced in the oxidative addition step reenters the catalytic cycle. 

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. 

The C(9)-C(14) segment VI was prepared by Steps D-l to D-3. The formation of the vinyl iodide in Step D-3 was difficult and proceeded in only 25-30% yield. The C(15)-C(21) segment VII was synthesized from the common intermediate 17 by Steps E-l to E-6. A DDQ oxidation led to formation of a 1,3-dioxane ring in Step E-l. The A-methoxy amide was converted to an aldehyde by LiAlH4 reduction and the chain was extended to include C(14) and C(15) using a boron enolate of an oxazo-lidinone chiral auxiliary. After reductive removal of the chiral auxiliary, the primary alcohol group was converted to a primary iodide. The overall yield for these steps was about 25%. 

This silyl hydrazone formation-oxidation sequence was originally developed as a practical alternative to the synthesis and oxidation of unsubstituted hydrazones by Myers and Furrow [31]. The formation of hydrazones directly from hydrazine and ketones is invariably complicated by azine formation. In contrast, silyl hydrazones can be formed cleanly from /V,/V -bis(7< rt-butyldimethylsilyl)hydrazine and aldehydes and ketones with nearly complete exclusion of azine formation. The resulting silylhydrazones undergo many of the reactions of conventional hydrazones (Wolff-Kishner reduction, oxidation to diazo intermediate, formation of geminal and vinyl iodides) with equal or greater efficiency. It is also noteworthy that application of hydrazine in this setting may also have led to cleavage of the acetate substituents. 

The stereoselective synthesis of the 12-acetoxy enone 428, related to the limonoid azadiradione, has been achieved in 12 steps (16% overall yield), starting from tricyclic diester 429. The key steps involve an intramolecular 1,3-dipolar cycloaddition of a nitrile oxide and a Stille coupling reaction of vinyl iodide with stannylfuran (469). 

Rawal s group developed an intramolecular aryl Heck cyclization method to synthesize benzofurans, indoles, and benzopyrans [83], The rate of cyclization was significantly accelerated in the presence of bases, presumably because the phenolate anion formed under the reaction conditions was much more reactive as a soft nucleophile than phenol. In the presence of a catalytic amount of Herrmann s dimeric palladacyclic catalyst (101) [84], and 3 equivalents of CS2CO3 in DMA, vinyl iodide 100 was transformed into ortho and para benzofuran 102 and 103. In the mechanism proposed by Rawal, oxidative addition of phenolate 104 to Pd(0) is followed by nucleophilic attack of the ambident phenolate anion on o-palladium intermediate 105 to afford aryl-vinyl palladium species 106 after rearomatization of the presumed cyclohexadienone intermediate. Reductive elimination of palladium followed by isomerization of the exocyclic double bond furnishes 102. 

Molander and Hiersemann (60) reported the preparation of the spirocyclic keto aziridine intermediate 302 in an approach to the total synthesis of (zb)-cephalotax-ine (304) via an intramolecular 1,3-dipolar cycloaddition of an azide with an electron-deficient alkene (Scheme 9.60). The required azide 301 was prepared by coupling the vinyl iodide 299 and the aryl zinc chloride 300 using a Pd(0) catalyst in the presence of fni-2-furylphosphine. Intramolecular 1,3-dipolar cycloaddition of the azido enone 301 in boiling xylene afforded the desired keto aziridine 302 in 76% yield. Hydroxylation of 302 according to Davis s procedure followed by oxidation with Dess-Martin periodinane delivered the compound 303, which was converted to the target molecule (i)-cephalotaxine (304). 

The following mechanism has been postulated. Cr(II) reduces Ni(Ii) to Ni(0). which undergoes oxidative addition to vinylic iodide 2ft. In the process, the Ni(0) species is transformed into a Ni(Il) compound, which is transmetallated by the resulting Cr(IIl) species to give 28. This compound then adds to the aldehyde, leading to ally lie alcohol 29... 

Chromium adds oxidatively not only to vinylic iodides, but also to allylic, aryl, and alkynyl iodides, as well as to CHE (see Chap ter 13).18 The corresponding triflates can be employed equally well. On the other hand the reactivity of bromides and chlorides is usually too limited. Reaction is carried out in the polar aprotic sol vent DMF because this is capable of dissolving both of the salts, and homogeneous conditions accelerate the reaction. 

The carbanion is trapped with iodine to give 42. which makes a further functionali/aiion possible. Conversion of vinylic iodide 42 into a lactone is accomplished by palladium-cataly/ed carbonyla-tion under Stille conditions.13 This process ean be broken down into the following elementary reactions a) Oxidative addition of Pd° to vinylic iodide 42 with formation of 43 b) An insertion reaction of carbon monoxide with creation of the pallada-acyl species 44 c) Reaction of acid-chloride equivalent 44 with the alcohol to give lactone 13. 

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. 

We later published an improved synthesis of tonkinecin because of the low yield of the coupling reaction between 11 and 12 (only 30% previously) in a previous study. One major reason is that the vinyl iodide 12 was not stable enough to survive the basic reaction conditions. An alternative for the synthesis of right-side segment was then designed, in which the vinyl iodide functionality was introduced in the last step to avoid those basic conditions (Scheme 10-7). The Wittig reaction of aldehyde 15 with 16 and subsequent hydrogenation afforded ester 17, which was converted to lactone 18 by aldol reaction with lactal followed by acid treatment and [(-elimination. Selective deprotection, Dess-Martin oxidation, and Takai reaction (to introduce the vinyl iodide) afforded the precursor 19. Similar treatments of 19 with 14, as well as subsequent intermediates as described previously, finally provided tonkinecin. 

Takahashi et al. also reported a route to muconin. Their synthesis adopted Keinan et al. s strategy to construct the stereochemistries by Sharpless AD and AE upon multiple olefin containing fatty acid (Scheme 10-35). The di-olefin 214 was subject to Sharpless AD conditions and then treated with acid, yielding a THP-containing diol. This diol was further protected as acetonide 215. The reversion of stereochemistry of alcohol 215 was achieved by Dess-Marlin oxidation and Zn(BH4)2 reduction. Williamson etherification of tosylate 216 and epoxide formation afforded tri-ring intermediate 217. Opening with acetylene, 217 was converted into the terminal alkyne 218, which was coupled with vinyl iodide to finally give muconin. 

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