Reduction cyclopropanes

Scheme 1. Generality of the titanium mediated reductive cyclopropanation of N,N-diakylcarboxamides. More than 60 compounds have been prepared by this route.

Scheme 24 Titanium-mediated intramolecular reductive cyclopropanation of N-aUyl-a-amino acid dimethylamides...

The starting material was trans-cyclopropane-1,2-dimethanol. The contiguous cyclopropane units were added by two iterative sequences of oxidation-Wadsworth-Emmons reduction-cyclopropanation. 

The reductive cyclopropanation with in situ generated titanacyclopropanes can also be applied to alkyldiformylamines 58, which are easily prepared from inexpensive formamide (57). Both formyl groups are converted to cyclopropyl groups, and the alkyldicyclopropyl-... 

Cyanopyridines undergo titanium-mediated reductive cyclopropanation to give pyridylcyclopropylamines in good yield <20030L753>. Both 2- and 3-cyanopyridine react with the titanium species 81 formed from diethylzinc and methyltriisopropyloxytitanium in the presence of lithium isopropoxide to give the cyclopropylamine product in 80% and 82% yield, respectively (Equation 55). 

The total synthesis of U-106305 (46) by Barret et al. [97] follows the same strategy as that of FR-900848 (45). In the synthesis of Charette and Lebel [98] the pentacyclopropane core (47) is prepared starting from the cyclopropane derived from trans-1,4-but-2-enediol by a tandem oxidation-Wittig olefination-reduction-cyclopropanation method. The Julia olefination of the corresponding monoaldehyde with benzothiazoylsulfone... 

Lithiumjliq. ammonia Reductive cyclopropane ring opening... 

Organozinc reagents are less nucleophilic than organomagnesium compounds and can be easily prepared with a variety of functional groups (see Chapter 7), several of them were tested for the reductive cyclopropanation of amides. Therefore, a new protocol was devised for the efficient preparation of various tert-butoxycar-bonyl and chloroalkylsubstituted cydopropylamine derivatives (Scheme 12.50) [70]. 

The majority of preparative methods which have been used for obtaining cyclopropane derivatives involve carbene addition to an olefmic bond, if acetylenes are used in the reaction, cyclopropenes are obtained. Heteroatom-substituted or vinyl cydopropanes come from alkenyl bromides or enol acetates (A. de Meijere, 1979 E. J. Corey, 1975 B E. Wenkert, 1970 A). The carbenes needed for cyclopropane syntheses can be obtained in situ by a-elimination of hydrogen halides with strong bases (R. Kdstcr, 1971 E.J. Corey, 1975 B), by copper catalyzed decomposition of diazo compounds (E. Wenkert, 1970 A S.D. Burke, 1979 N.J. Turro, 1966), or by reductive elimination of iodine from gem-diiodides (J. Nishimura, 1969 D. Wen-disch, 1971 J.M. Denis, 1972 H.E. Simmons, 1973 C. Girard, 1974),... 

The growing importance of cyclopropane derivatives (A. de Meijere, 1979), as synthetic intermediates originates in the unique, olefin-like properties of this carbocycle. Cyclopropane derivatives with one or two activating groups are easily opened (see. p. 69f.). Some of these reactions are highly regio- and stereoselective (E. Wenkert, 1970 A, B E. J. Corey, 1956 A, B, 1975 see p. 70). Many appropriately substituted cyclopropane derivatives yield 1,4-difunctional compounds under mild nucleophilic or reductive reaction conditions. Such compounds are especially useful in syntheses of cyclopentenone derivatives and of heterocycles (see also sections 1.13.3 and 4.6.4). 

The hydrogenolyaia of cyclopropane rings (C—C bond cleavage) has been described on p, 105. In syntheses of complex molecules reductive cleavage of alcohols, epoxides, and enol ethers of 5-keto esters are the most important examples, and some selectivity rules will be given. Primary alcohols are converted into tosylates much faster than secondary alcohols. The tosylate group is substituted by hydrogen upon treatment with LiAlH (W. Zorbach, 1961). Epoxides are also easily opened by LiAlH. The hydride ion attacks the less hindered carbon atom of the epoxide (H.B. Henhest, 1956). The reduction of sterically hindered enol ethers of 9-keto esters with lithium in ammonia leads to the a,/S-unsaturated ester and subsequently to the saturated ester in reasonable yields (R.M. Coates, 1970). Tributyltin hydride reduces halides to hydrocarbons stereoselectively in a free-radical chain reaction (L.W. Menapace, 1964) and reacts only slowly with C 0 and C—C double bonds (W.T. Brady, 1970 H.G. Kuivila, 1968). 

The reaction of benzoyl chloride with (Me3Si)2 affords benzoyltrimethylsi-lane (878)[626,749,750]. Hexamethyldigermane behaves similarly. The siloxy-cyclopropane 879 forms the Pd homoenolate of a ketone and reacts with an acyl halide to form,880. The 1,4-diketone 881 is obtained by reductive elimination of 880 without undergoing elimination of /7-hydrogen[751]. 

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