Cyclopropane ring systems synthesis

The formation of cyclopropanes by the addition of carbenes to alkenes was first reported by Doering and Hoffmann in 1954/ Since then, this most characteristic reaction of carbenes has been successfully exploited for the synthesis of cyclopropanes. The cyclopropane ring system is not only found as a structural element in a wide range of natural products, but is also a very useful synthetic intermediate leading to a variety of cyclic and acyclic compounds. ... 

These results can be interpreted in terms of competition between recombination of the diradical intermediate and conformational equilibration, which would destroy the stereochemical relationships present in the azo compound. The main synthetic application of azo compound decomposition is in the synthesis of cyclopropanes and other strained-ring systems. Some of the required azo compounds can be made by 1,3-dipolar cycloadditions of diazo compounds (see Section 6.2). 

The electrochemical reduction of 1,3-dibromides to cyclopropanes (30 31) appears to be fairly general 4J 44> an(j has been applied to the synthesis of some rather strained ring systems, e.g., 32, 33, and 34. Rifi has sug-... 

An example, where two C-C-bonds are formed and one C-C-bond is broken is the synthesis of the tricycle 3-285, which has some similarity with the eudesmane framework 3-286, developed by Kilburn and coworkers (Scheme 3.72) [113]. Thus, exposure of the easily accessible methylenecyclopropyl-cyclohexanone 3-281 to samarium(II) iodide led to the generation of ketyl radical 3-282, which builds up a six-membered ring system with simultaneous opening of the cyclopropane moiety. Subsequent capture of the formed radical 3-283 by the adjacent alkyne group afforded the tricycle 3-285 via 3-284 as a single diastereoisomer in up to 60% yield. It should be noted that in this case the usual necessary addition of HMPA could be omitted. 

The di-rc-methane rearrangement is also a convenient way of obtaining polycyclic fused ring systems as illustrated in the synthesis of a tricyclo-undecane (3.17) 327). In the irradiation of dihydrotriquinacene the initial bonding scheme is identical as in (3.14) but ultimate cyclopropane formation is hindered by structural reasons (3.18) 328). 

A total synthesis of the sesquiterpene ( )-illudin C 420 has been described. The tricyclic ring system of the natural product is readily quickly assembled from cyclopropane and cyclopentene precursors via a novel oxime dianion coupling reaction and a subsequent intramolecular nitrile oxide—olefin cycloaddition (463). 

A classical application of cyclopropane rings in "reactivity inversion", in which a previously negatively polarised y-carbon atom (see 29) to a carbonyl group is inverted by formation of a cyclopropane ring (30) and is then intramolecularly attacked by a nucleophilic aromatic ring, is found in the synthesis of hydrophenanthrene system 11 (Scheme 5.19) developed by Stork in 1969 [21]. 

Miscellaneous Iminium Catalyzed Transformations The enantioselective construction of three-membered hetero- or carbocyclic ring systems is an important objective for practitioners of chemical synthesis in academic and industrial settings. To date, important advances have been made in the iminium activation realm, which enable asymmetric entry to a-formyl cyclopropanes and epoxides. In terms of cyclopropane synthesis, a new class of iminium catalyst has been introduced, providing the enantioselective stepwise [2 + 1] union of sulfonium ylides and ot,p-unsaturated aldehydes.As shown in Scheme 11.6a, the zwitterionic hydro-indoline-derived catalyst (19) enables both iminium geometry control and directed electrostatic activation of sulfonium ylides in proximity to the incipient iminium reaction partner. This combination of geometric and stereoelectronic effects has been proposed as being essential for enantio- and diastereocontrol in forming two of the three cyclopropyl bonds. 

Another enantiospecific synthesis of longifolene was done starting with camphor, a natural product available in enantiomerically pure form (Scheme 13.26). The tricyclic ring system is formed in step C by an intramolecular Mukaiyama reaction. The dimethyl substituents are formed in the first step of sequence E by hydrogenolysis of the cyclopropane ring. The final step of the synthesis involves a rearrangement of the tricyclic ring system that is induced by solvolysis of the mesylate intermediate. 

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). ... 

Main group metals and transition metals play an important role in cyclopropane synthesis. This section discusses cyclopropane synthesis via release of the ring system from transition-metal complexes. Only methods starting from isolable or potentially isolable transition-metal complexes are included. For other methods of cyclopropane synthesis involving transition-metal complexes as reagents or as reactive intermediates, see Sections l.C (Coordination Chemistry of Cyclopropanes). 

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