Nature alkynes

Many natural products contain alkynes, which contain one or more triple bonds. Many natural alkynes contain several triple bonds and are physiologically active. For example, the skin of a species of frog that lives in the Lower Amazon Basin secretes a mucous membrane irritant that wards off predators. This compound is an alkyne with three triple bonds, a triyne, called ichthyothereol. The Indians of the area coat their arrowheads with the secretion. When the arrow pierces the skin of the prey, the compound acts on the nervous system and causes convulsions. 

The 1,3-dipolar molecules are isoelectronic with the allyl anion and have four electrons in a n system encompassing the 1,3-dipole. Some typical 1,3-dipolar species are shown in Scheme 11.4. It should be noted that all have one or more resonance structures showing the characteristic 1,3-dipole. The dipolarophiles are typically alkenes or alkynes, but all that is essential is a tc bond. The reactivity of dipolarophiles depends both on the substituents present on the n bond and on the nature of the 1,3-dipole involved in the reaction. Because of the wide range of structures that can serve either as a 1,3-dipole or as a dipolarophile, the 1,3-dipolar cycloaddition is a very useful reaction for the construction of five-membered heterocyclic rings. 

Two new sections on the protection of phosphates and the alkyne-CH are included. All other sections of the book have been expanded, some more than others. The section on the protection of alcohols has increased substantially, reflecting the trend of the nineties to synthesize acetate- and propionate-derived natural products. An effort was made to include many more enzymatic methods of protection and deprotection. Most of these are associated with the protection of alcohols as esters and the protection of carboxylic acids. Here we have not attempted to be exhaustive, but hopefully, a sufficient number of cases are provided that illustrate the true power of this technology, so that the reader will examine some of the excellent monographs and review articles cited in the references. The Reactivity Charts in Chapter 10 are identical to those in the first edition. The chart number appears beside the name of each protective group when it is first introduced. No attempt was made to update these Charts, not only because of the sheer magnitude of the task, but because it is nearly impossible in... 

First, attempt to identify the most acidic hydrogen in the starting material, based on hybridization or on the nature of neighboring atoms. Explain your rationale. Next, examine the electrostatic potential map for starting material alkyne). Which hydrogen appears to be most electron poor Is this the one that you predicted What makes this hydrogen more electron poor than the others ... 

A -Methylpyrrole oxidatively adds to [Ru(C=C=C=CH2)(PPli3)2(Cp)][PF6] via its C2 center, the product being the allenylidene species 38 [98JCS(D)467]. Alkyne mesomeric form 39 was postulated to make a significant contribution, which explains well the nature of the deprotonated product 40, obtained from 38 and n-butyllithium. 

The reaction time between 4-iodopyrazoles and 1-alkynes varies from 5 to 25 h and the yield of products is 55-95%. It is noteworthy that the nature of the terminal acetylene has a greater effect on the rate of halogen atom substitution for low-reactive 4-iodopyrazoles. Thus, the reaction time for ethynylarenes is 5-6 h, and for less acidic aliphatic 1-alkynes is 10-25 h (Table XTT). 

The synthetic value of the Dotz reaction has for example been demonstrated by the synthesis of vitamin Ki(20) 10 (simplified structure). This natural product has been prepared synthetically from the chromium carbene complex 8 and the alkyne 9 in two steps the second step being the oxidative decomplexation to yield the free product 10 ... 

The total synthesis of ( )-estrone [( )-1 ] by Vollhardt et al. is a novel extension of transition metal mediated alkyne cyclotrimeriza-tion technology. This remarkable total synthesis is achieved in only five steps from 2-methylcyclopentenone (19) in an overall yield of 22%. The most striking maneuver in this synthesis is, of course, the construction of tetracycle 13 from the comparatively simple diyne 16 by combining cobalt-mediated and ort/io-quinodimethane cycloaddition reactions. This achievement bodes well for future applications of this chemistry to the total synthesis of other natural products. 

Other examples of [2C+2S+1C0] cycloaddition reactions have been described by Herndon et al. by the use of chromium cyclopropyl(methoxy)carbenes. These complexes react with alkynes releasing ethene and forming cyclopenta-dienone derivatives, which evolve to cyclopentenone derivatives in the presence of chromium(O) and water [122] (Scheme 76). This reaction has been extended to intramolecular processes and also to the synthesis of some natural products [123]. These authors have also described another process involving a formal [2C+2S+1C0] cycloaddition reaction. Thus, the reaction of methyl and cyclo-propylcarbene complexes with phenylacetylene derivatives does not afford the expected benzannulated products, and several regioisomers of cyclopentenone derivatives are the only products isolated [124] (Scheme 76). 

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. 

Scheme 94 Total synthesis of the natural compound dehydrohomoancepsenolide (473) through sequential application of chemoselective ruthenium-catalyzed RCM and tungsten-catalyzed alkyne homodimerization [191]...

Lindel T (2003) Alkyne metathesis in natural product synthesis. In Schmalz HG, Wirth T (eds) Organic synthesis highlights, vol V. Wiley-VCH, Weinheim, p 27... 

The addition of (TMS)3SiH to a number of monosubstituted acetylenes has also been studied in some detail. These reactions are highly regioselective (anti-Markovnikov) and give terminal (TMSlsSi-substituted alkenes in good yields. High cis or trans stereoselectivity is also observed, depending on the nature of the substituents at the acetylenic moiety. For example, the reaction of the alkynes 23 and 24 with (TMSlsSiH, initiated either by EtsB at room temperature (method or by thermal decomposition of di-ferf-butyl peroxide at 160 °C... 

The product of the rearrangement may be stable or may react further, depending on its nature (see also pp. 1396). An ab initio study predicts that a [l,2]-alkyl shift in alkyne anions should be facile. ... 

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