3,4-Unsaturated 1,5-diynes

The Ratnberg-Backlund reaction has been used for the preparation of strained unsaturated ring compounds that are difficult to obtain by other methods. A recent example is the synthesis of ene-diyne 5" that has been used as starting material for a Bergman cyclization ... 

Depending on the types of unsaturated functional units involved in the metathesis process, the reactions can be classified into three major categories diene, enyne, and diyne metathesis (Figs. 1-3). Another mode of classification... 

An obvious drawback in RCM-based synthesis of unsaturated macrocyclic natural compounds is the lack of control over the newly formed double bond. The products formed are usually obtained as mixture of ( /Z)-isomers with the (E)-isomer dominating in most cases. The best solution for this problem might be a sequence of RCAM followed by (E)- or (Z)-selective partial reduction. Until now, alkyne metathesis has remained in the shadow of alkene-based metathesis reactions. One of the reasons maybe the lack of commercially available catalysts for this type of reaction. When alkyne metathesis as a new synthetic tool was reviewed in early 1999 [184], there existed only a single report disclosed by Fiirstner s laboratory [185] on the RCAM-based conversion of functionalized diynes to triple-bonded 12- to 28-membered macrocycles with the concomitant expulsion of 2-butyne (cf Fig. 3a). These reactions were catalyzed by Schrock s tungsten-carbyne complex G. Since then, Furstner and coworkers have achieved a series of natural product syntheses, which seem to establish RCAM followed by partial reduction to (Z)- or (E)-cycloalkenes as a useful macrocyclization alternative to RCM. As work up to early 2000, including the development of alternative alkyne metathesis catalysts, is competently covered in Fiirstner s excellent review [2a], we will concentrate here only on the most recent natural product syntheses, which were all achieved by Fiirstner s team. 

Notice that an is used to indicate the absence of a double bond or triple bond, such as in pentane above. If there are two double bonds in a compound, then the unsaturation is -dien-. Three double bonds is -trien-. Similarly, two triple bonds is -diyn-, and three triple bonds is -triyn-. For multiple double and triple bonds, we use the following terms ... 

A hydrosilylation/cyclization process forming a vinylsilane product need not begin with a diyne, and other unsaturation has been examined in a similar reaction. Alkynyl olefins and dienes have been employed,97 and since unlike diynes, enyne substrates generally produce a chiral center, these substrates have recently proved amenable to asymmetric synthesis (Scheme 27). The BINAP-based catalyst employed in the diyne work did not function in enyne systems, but the close relative 6,6 -dimethylbiphenyl-2,2 -diyl-bis(diphenylphosphine) (BIPHEMP) afforded modest yields of enantio-enriched methylene cyclopentane products.104 Other reported catalysts for silylative cyclization include cationic palladium complexes.105 10511 A report has also appeared employing cobalt-rhodium nanoparticles for a similar reaction to produce racemic product.46... 

In Section 9.2, intermolecular reactions of titanium—acetylene complexes with acetylenes, allenes, alkenes, and allylic compounds were discussed. This section describes the intramolecular coupling of bis-unsaturated compounds, including dienes, enynes, and diynes, as formulated in Eq. 9.49. As the titanium alkoxide is very inexpensive, the reactions in Eq. 9.49 represent one of the most economical methods for accomplishing the formation of metallacycles of this type [1,2]. Moreover, the titanium alkoxide based method enables several new synthetic transformations that are not viable by conventional metallocene-mediated methods. 

For a number of other pharmacologically active unsaturated compounds, it is assumed that a reactive allene is formed in situ by an alkyne isomerization [160] or an elimination reaction [161]. The prime example of the formation of such a highly reactive allene through chemical activation of an unsaturated precursor is the ene-diyne antibiotic neocarzinostatin (Scheme 18.57) [162],... 

Complexes of other metals are also capable of catalyzing useful carbonylation reactions under phase transfer conditions. For example, certain palladium(o) catalysts, like Co2(C0)g, can catalyze the carbonylation of benzylic halides to carboxylic acids. When applied to vinylic dibromides, unsaturated diacids or diynes were obtained, using Pd(diphos)2[diphos l,2-bis(diphenylphosphino)ethane] as the metal catalyst, benzyltriethylammonium chloride as the phase transfer agent, and t-amyl alcohol or benzene as the organic phase(18),... 

Reduction of aromatic rings 5-15 Cyclization of dienes or diynes 5-18 Cyclization of unsaturated Grignard... 

Concerning chemical selectivities in multiple unsaturated acetylenic compounds, conjugated enynes are reduced with modest selectivity. The most difficult case involves the selective reduction of an enyne with a terminal double bond and an internal triple bond, because the difference in the rates of their hydrogenation is minimal. The hydrogenation of nonterminal, unconjugated diynes to (Z,Z)-dienes can be achieved in good yield. 

The pyridazine dioxide derivative (108) was made by intramolecular nitroso compound dimerization as shown (Scheme 23). 1,2-Oxathiin 2,2-dioxides are obtained by the addition of sulfuric acid to a,(3-unsaturated ketones, e.g. (109) — (110) (66HC(21-2)774). 1,2-Dithiins are synthesized from conjugated diynes using benzyl thiol reductive debenzylation of intermediate (111) by sodium in liquid ammonia at - 70°C gives, after aerial oxidation, the 1,2-dithiin (112) (67AG(E)698). 

Keywords active methylene compound, unsaturated alkyl halide, alumina, potassium tert-butoxide, 4,4-bis-functionalized 1,6-diene, 1,6-diyne... 

A stereochemical study of the synthesis of unsaturated 1,4-aminoalcohols via the reaction of unsaturated 1,4-alkoxyalcohols with chorosulfonyl isocyanate revealed a competition between an retentive mechanism and an SnI racemization mechanism, with the latter having a greater proportion with systems where the carbocation intermediate is more stable.254 An interrupted Nazarov reaction was observed, in which a nonconjugated alkene held near the dienone nucleus undergoes intramolecular trapping of the Nazarov cyclopentenyl cation intermediate.255 Cholesterol couples to 6-chloropurine under the conditions of the Mitsunobu reaction the stereochemistry and structural diversity of the products indicate that a homoallylic carbocation derived from cholesterol is the key intermediate.256 l-Siloxy-l,5-diynes undergo a Brpnsted acid-promoted 5-endo-dig cyclization with a ketenium ion and a vinyl cation proposed as intermediates.257... 

A two-step synthesis of arenediynes from arene-1,2-dialdehydes has been reported (Scheme 15). Dibromomethylenation of dialdehydes under Corey-Fuchs conditions provides the tetrabromides, which on treatment with n-BuLi or LDA afford 3,4-unsaturated 1,5-diynes, the key structural moiety present in several naturally occurring... 

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