Hass cyclopropane process

Freund Reaction Gustavson Reaction Hass Cyclopropane Process... 

Formation of al icy die hydrocarbons by the action of sodium (Freund reaction) or zinc (Gustavson reaction) on open chain dihalo compounds 1,3-dichloropropane derived from the chlorination of propane obtained from natural gas is cyclized in the Hass cyclopropane process by treating with zinc dust in aqueous alcohol in the presence of catalytic sodium iodide ... 

In recent years, the variety of useful diazo substrates for asymmetric intramolecular cyclopropanation processes has really expanded. As another example, Charette and Wurz have reported the first example of an intramolecular cyclopropanation involving a-nitro-a-diazo carbonyl compounds.This reaction, catalysed by Rh2[(S)-DOSP]4, led to the formation of nine-membered nitrocyclopropyl lactones in good yields and enantioselectivities with extremely high diastereoselectivities (Scheme 6.17). This novel methodology constituted an efficient entry into chiral functionalised macrocyclic-fused cyclopropane oc-amino acids. 

Metal catalysed decomposition of diazocarbonyl compounds in the presence of alkenes provides a facile and powerful means of constructing electrophilic cyclopropanes. The cyclopropanation process can proceed intermolecularly or intramolecularly. Early work on the topic of intramolecular cyclopropanation (mainly using diazoketones as precursors) has been surveyed31. With the discovery of powerful group VIII metal catalysts, in particular the rhodium(II) derivatives, metal catalysed cyclopropanation of diazocarbonyls is currently the most fertile area in cyclopropyl chemistry. In this section, we will review the efficiency and versatility of the various catalysts employed in the cyclopropanation of diazocarbonyls. Cyclopropanations have been organized according to the types of diazocarbonyl precursors. Emphasis is placed on recent examples. 

Intramolecular cyclopropanation of diazoketones to furnish [3.1.0] and [4.1.0] bicyclic systems are the most common and effective reactions in this category. Two recent examples are shown in equations 48 and 49. The bicyclic ketone 34 has been used in the synthesis of polycyclic cyclobutane derivatives77, whereas ketone 35 is the key intermediate in the total synthesis of ( )-cyclolaurene78. When the olefinic double bond is attached to, or is part of, a ring system, the cyclopropanation process also works well. Copper oxide catalysed decomposition of diazoketone 36 produces the strained tricyclic ketone 37 in 86% yield (equation 50)79. In another case, in which the cyclopropanation of diazoketone 38 gave stereospecifically the cyclopropyl ketone 39, copper sulphate catalysis was used. The cyclopropyl ketone 39 is the key intermediate in the total synthesis of ( )-albene 40 (equation 51). ... 

Finally, a racemic cyclopropanation process has also been developed that utilizes an iron Lewis acid catalyst (72) that presumably proceeds through an iron carbene intermediate (73) (Scheme 28). The catalyst is activated by reaction with diazo compounds to produce an intermediate (74) that loses dinitrogen see Dinitrogen Dinitrogen Complexes) to afford the cyclopropane. This chemistry has been extended to the production of epoxides and aziridines and has recently been reviewed. ... 

A highly convenient and versatile cyclopropanation method has been devised which involves treatment of olefins with different organoaluminum compounds and alkylidene iodide under mild conditions [93]. Although Miller found that cyclopropane formation by use of EtsAl-methylene iodide in cyclohexene proceeds in quite disappointing yields [94], Yamamoto and Maruoka reached the conclusion that the intermediate dialkyl(iodomethyl)aluminum species 97 is responsible for the cyclopropanation of olefins and that it readily decomposes in the absence of olefins or in the presence of excess trialkylaluminum. Hence the use of equimolar amounts of trialkyl-aluminum and methylene iodide in the presence of olefins is essential for the achievement of reproducible results in the cyclopropanation process. In addition, because di-alkylaluminum halide can also be used as a cyclopropanation agent, the use of half an equivalent of trialkylaluminum is not detrimental (Sch. 61). 

The substrate scope of transition metal-catalysed cyclopropanation reactions has been further widened. Allene-containing diazomalonates (49) have been shown to undergo an intramolecular cyclopropanation process under Cu(I)-catalysis, thus furnishing bicyclic methylenecyclopropanes (50) with a moderate level of diastereoselectivity (up to 8.3 1 More interestingly, substrates (49) have exhibited another reactivity... 

In addition to developments with ylides in asymmetric cyclopropanation reactions, there have been promising reports involving other unrelated cyclopropanation processes. Corey has documented exciting results in a study of the Kulinkovic reaction (Equation 24) [84], This reaction involves the addition of Grignard reagents to esters in the presence of Ti(Oi-Pr)4 to afford cyclopropanols [85]. Corey demonstrated that when the reaction was conducted in the presence of bis(TADDOL)Ti complex 143, enantioenriched products 144 were obtained (up to 78 % ee) [84]. This method provides an important entry point to chiral cyclopropanols, a class of products not otherwise conveniently accessible in optically active form. 

It is thus anticipated that compressive stress inhibits while tensile stress promotes chemical processes which necessitate a rehybridization of the carbon atom from the sp3 to the sp2 state, regardless of the reaction mechanism. This tendency has been verified for model ring-compounds during the hydrogen abstraction reactions by ozone and methyl radicals the abstraction rate increases from cyclopropane (c3) to cyclononane (c9), then decreases afterwards in the order anticipated from Es [79]. The following relationship was derived for this type of reactions ... 

Although the intramolecular cyclopropanation of simple alkenes easily occurs in those cases where a five- or six-membered ring is formed in addition to the three-membered ring [13], the intermolecular version of this process was described by Barluenga et al. in 1997 [ 14c]. Thus, this reaction has shown a high... 

Tl(III) < Pb(IV), and this conclusion has been confirmed recently with reference to the oxythallation of olefins 124) and the cleavage of cyclopropanes 127). It is also predictable that oxidations of unsaturated systems by Tl(III) will exhibit characteristics commonly associated with analogous oxidations by Hg(II) and Pb(IV). There is, however, one important difference between Pb(IV) and Tl(III) redox reactions, namely that in the latter case reduction of the metal ion is believed to proceed only by a direct two-electron transfer mechanism (70). Thallium(II) has been detected by y-irradiation 10), pulse radiolysis 17, 107), and flash photolysis 144a) studies, butis completely unstable with respect to Tl(III) and T1(I) the rate constant for the process 2T1(II) Tl(III) + T1(I), 2.3 x 10 liter mole sec , is in fact close to diffusion control of the reaction 17). 

Apart from the cyclopropanation reaction, only one example has been published of the application of ionic liquids as reaction media for enantio-selective catalysis with bis(oxazoline) ligands. In this case, the complex 6b-ZnCl2 was used as a catalyst for the Diels-Alder reaction between cyclopen-tadiene and N-crotonyloxazolidin-2-one in dibutyUmidazoUiun tetrafluorob-orate (Scheme 9) [48]. Compared with the same process in CH2CI2, the reaction was faster and both the endofexo selectivity and the enantioselectivity in the endo product were excellent. However, experiments aimed at recovering the catalysts were not carried out. 

Some years ago we began a program to explore the scope of the palladium-catalyzed annulation of alkenes, dienes and alkynes by functionally-substituted aryl and vinylic halides or triflates as a convenient approach to a wide variety of heterocycles and carbocycles. We subsequently reported annulations involving 1,2-, 1,3- and 1,4-dienes unsaturated cyclopropanes and cyclobutanes cyclic and bicyclic alkenes and alkynes, much of which was reviewed in 1999 (Scheme l).1 In recent days our work has concentrated on the annulation of alkynes. Recent developments in this area will be reviewed and some novel palladium migration processes that have been discovered during the course of this work will be discussed. 

It has been pointed out earlier that the anti/syn ratio of ethyl bicyclo[4.1,0]heptane-7-carboxylate, which arises from cyclohexene and ethyl diazoacetate, in the presence of Cul P(OMe)3 depends on the concentration of the catalyst57). Doyle reported, however, that for most combinations of alkene and catalyst (see Tables 2 and 7) neither concentration of the catalyst (G.5-4.0 mol- %) nor the rate of addition of the diazo ester nor the molar ratio of olefin to diazo ester affected the stereoselectivity. Thus, cyclopropanation of cyclohexene in the presence of copper catalysts seems to be a particular case, and it has been stated that the most appreciable variations of the anti/syn ratio occur in the presence of air, when allylic oxidation of cyclohexene becomes a competing process S9). As the yields for cyclohexene cyclopropanation with copper catalysts [except Cu(OTf)2] are low (Table 2), such variations in stereoselectivity are not very significant in terms of absolute yields anyway. 

The photoelimination of nitrogen from 1-pyrazolines is one of the most thoroughly investigated photoreactions and it has been used extensively in the synthesis of cyclopropane derivatives.334 Both stereospecific and non-stereospedfic processes have been observed and these are believed, at least in simple 1-pyrazolines, to correspond to singlet and triplet excited states, respectively. Two reaction pathways have been proposed in the azoalkane 405335 direct excitation via a thermally activated S, state affords the C6H6 isomers 406 to 409, whereas triplet-sensitized excitation results in a tem-... 

As opinions regarding the metathesis reaction pathway have shifted in recent years to favor a nonpairwise carbene-to-metallocyclobutane transformation, increasing attention has been given to the mechanistic significance of cyclopropane olefin interconversions. This interconversion process seems to occur primarily when certain relatively inefficient catalysts are employed, which in itself raises questions. Under ideal conditions, "good metathesis catalysts are remarkably efficient promoters of transalkylidenation, and consequently are well suited for olefin and polymer syntheses. Thus, most early studies focused primarily on applications. When side reactions did occur, they were usually ignored or presumed to be trivial cationic processes. 

---