Double Alkenylation Reactions

Pd(OAc)2, PPh3, (Z) isomer accesible by MeCN, 90% reversing order of crosscouplings 

A recent example is the synthesis by Ichikawa and coworkers [15] of a single tetra-fluoro[3]dendralene via double Negishi cross-coupling of 2,2-difluorovinylzinc bromide to a dibromoolefin. 

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To date, only double Heck reactions have been described, but triple Heck reactions are also possible [39]. Reaction of the alkynyl aryl iodide 6/1-55 with norbor-nene in the presence of Pd(OAc)2, triphenylphosphane and triethylamine as base led to the cyclopropanated norbornene derivate 6/1-59 as a single diastereomer in 40% yield (Scheme 6/1.13). It can be assumed that the alkenyl Pd-species 6/1-56 is first formed stereoselectively, and this undergoes a Heck reaction with norbornene... 

Suitably positioned vinyl halide can undergo Heck-type intramolecular coupling to generate dienes (equations 124 and 125)216,217. When one of the reacting partners in the Heck reaction is a diene, trienes are obtained (equation 126)218. Heck coupling of ally lie alcohols and alkenyl iodides has been employed for the synthesis of vitamin A and related compounds (equation 127)219,220. A similar double Heck reaction on a Cio-diiodide with a Cis-allylic alcohol leads to -carotene as a mixture of isomers (equation 128)209e. 

The alkenylation reaction of ct-halo carbonyl compounds with alkenylindium in the presence of triethylborane proceeds via a radical process. Unactivated alkene moieties as well as a styryl group can be introduced by this method. The geometry of the carbon-carbon double bonds of the alkenylindium is retained. Preparation of alkenylindium via hydroindation of 1-alkyne followed by the radical alkenylation establishes an efficient one-pot strategy (Scheme 113).384... 

Alkenyl double-bond migration [7] and geometrical isomerization [77] are sometimes observed when alkenyl reaction components are used, especially for allyhc and (Z)-alkenyl components under harsh conditions (Sects. 4.2 and 4.8). 

Likewise, alkynes undergo similar reactions to produce alkenyl complexes, however, both single- and double-insertion reactions can occur (Scheme 12). A surprising feature of the double-insertion... 

Distannylethenes are traditionally prepared by the free-radical addition of a tin hydride to a vinyltin the bis(tributylstannyl) derivative has been used in either single or double coupling reactions, for example by Echavairen and co-workers [52,53], who reacted it with acid chlorides, and Barrett et al. [54], who coupled it sequentially with alkenyl iodides. 

Heck reaction is a diene, trienes are obtained (equation l26). Heck coupling of allylic alcohols and alkenyl iodides has been employed for the synthesis of vitamin A and related compounds (equation A similar double Heck reaction on a Cio-diiodide with... 

The use of diethyl l-(ethoxycarbonyl)vinylphosphonate is based on Michael addition of anionic nucleophiles to the double bond to produce stabilized phosphonate anions capable of undergoing subsequent alkenylation reaction with aldehydes or ketones by a Homer-Wadsworth-Emmons process (Scheme 8.27)." 2 " "... 

Further, Li reported an analogous Cu(I)-catalyzed double alkenylation of amides 304 with 1,4-diiodo-l,3-dienes 303 leading to the formation of tri- and tetra-substi-tuted N-acylpyrroles 30S (Scheme 8.108) [306]. Interestingly, in contrast to Buchwald s approach, employment of alkylcarbamates as the N-nudeophile components in a catalytic reaction provided low yields of the pyrrole products. However, this limitation could be alleviated by performing the reaction in the presence of stoichiometric amounts of Cul and 1,2-diamine ligand L. 

With Zn Lewis acids, only single a-insertion of alkynes (—> 42) is observed, while with AlMes double alkenylation (— 43) dominates. It is proposed that oxidative Ni(0) insertion to the 2-CH bond, hydronickelation of the triple bond, alkenyl transfer to C-2 of the pyridine, and reductive Ni-elimination are the decisive steps in the catalytic cycle, (d) The pyridyl residue may serve as a directing group in C-H insertion reactions of phenyl substituents at pyridine mediated by transition metals like Cu and Pd. For instance, 2-phenylpyridine can be regioselectively halogenated, acetoxylated, and cyanided (- products 44, 45, and 47) in the presence of Cu(OAc)2 [92] or amidated — 46) in the presence of Pd(OAc)2 [93] ... 

A double Peterson alkenylation reaction has been successfully conducted using two equivalents of the lithium anion of trimethylsilylacetonitrile, generated with n-BuLi, and the 5,5-dithianeno-nanedial shown in equation eq 15, affording the corresponding (Z,Z)-o, )3-unsaturated dinitrile isomer in 73% yield. The residual material was assigned to the (.Zff)-stereoisomer. ... 

The highly selective sy/j-double arylation or alkenylation reaction of alkynes or alkenes with aryl or alkenylstannane reagents was realized via a possible oxidative addition, insertion, transmetalation, and reductive elimination mechanism (eqs 31 and 32). ... 

The double alkenylation approach (Scheme 1.1) has only been exploited relatively recently, most probably because of the rise to prominence of cross-coupling methodologies in recent times. The first double cross-couplings between 1,1-dihaloalkenes and metalloalkenes were isolated examples appearing in 1998 [9] and 2000 [10]. In 2002, Oh and Lim [11] reported a series of double Suzuki-Miyaura reactions between a 1,1-dibromoalkene 6 and alkenyl boronic acids 7 (Scheme 1.2). In 2007 and 2008, the Sherburn research group reported syntheses of substituted [3] dendralenes [12] and the state-of-the-art synthesis of [5]dendralene [13] respectively, transforming a 1,1-dihaloalkene via double... 

A study has been reported regarding the ruthenium-catalysed reaction of benza-mides with alkynes, which yields ort/io-alkenylated derivatives. Here, the mechanism is likely to involve rate-limiting metalation, followed by alkyne insertion to form intermediates such as (63) which on protonolysis yield the alkenylated products. An allylic carbon-carbon double bond has also been used as a coordination site in palladium-catalysed alkenylation reactions, as shown in Scheme 3. Here measurement of kinetic isotope effects suggests that coordination of the palladium with the allylic double bond occurs before palladation to give (64). Insertion of the alkene into the carbon-palladium bond gives (65) and -hydride elimination " leads to the product... 

The alkenyloxirane 126 in excess reacts with aryl and alkenyl halides or triflates in the presence of sodium formate to afford the allylic alcohol 127[104], Similarly, the reaction of the alkenyloxetane 128 gives the homo-allylic alcohol 130[105]. These reactions can be explained by insertion of the double bond in the Ar—Pd bond, followed by ring opening (or /3-eliraination) to form the allylic or homoallylic alkoxypalladium 129, which is converted into the allylic 127 or homoallylic alcohol 130 by the reaction of formate. The 3-alkenamide 132 was obtained by the reaction of the 4-alkenyl-2-azetizinone 131 with aryl iodide and sodium formate [106]. 

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. 

Double dehydrohalogenation of gemmal dihalides (Section 9 7) An E2 elimination reaction of a gemmal dihalide yields an alkenyl halide If a strong enough base IS used sodium amide for example a second elimination step follows the first and the alkenyl halide IS converted to an alkyne... 

The double bond m the alkenyl side chain undergoes addition reactions that are typical of alkenes when treated with electrophilic reagents... 

Section 11 16 Addition reactions to alkenylbenzenes occur at the double bond of the alkenyl substituent and the regioselectivity of electrophilic addition is governed by carbocation formation at the benzylic carbon See Table 11 2... 

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