Ring-opening Reactions with Electrophiles

Kocovsky and V. Cerny, Collect. Czech. Chem. Commun., 1980, 45, 3190. 

Cyclization Reactions of Oxirans. The search for non-enzymatic cyclizations of squalene oxide and its analogues continues with the report of the direct sterol synthesis of (128) (2%) from (127). Although the yield is low, the procedure involving treatment of (127) in CH2CI2 that contains BF3 -OEt2 and ethene carbonate at 0°C for 20 minutes affords four new rings and seven new asymmetric centres in one laboratory operation. The diepoxide 

Bellucci, G. Berti, R. Bianchini, G. Ingrosso, and A. Moroni, J. Chem. Soc., Perkin Trans. 2. 1981, 1336. 

Other examples of cyclization reactions involving alkenyl groups are the formation of the pentacyclic ether (133) from the BF3 OEt2-catalysed rearrangement of (132) and the transannular cyclization of humulene 9,10-oxide (134) to (135) (70%) in BF3 OEt2-acetic anhydride.  

Shirahama, K. Hayano, Y. Kanemoto, S. Misumi, T. Ohtsuka, N. Hashiba, 

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Diethyl cyclopropane-1,1-dicarboxylate underwent a nucleophilic ring-opening reaction with disodium tetracarbonylferrate in which one of the carbon monoxide ligands acted as a C-nucleo-phile. The intermediate iron complex reacted with electrophiles such as protons or iodomethane to give y-oxopropanedioates. ... 

The less reactive, weak electrophilic azetidinium ions undergo ring-opening reactions with charged nucleophiles such as carboxyl ions. The reaction of PTHF with thiolane gives similar results (307). 

Acylations were often carried out with diaziridines. Twofold acylation is normally observed when two NH groups are present. Most acylations were performed with benzoyl chloride, acetyl chloride or phenyl isocyanate (B-67MI50800). Ring opening reactions during acylation, foreseeable for intermediates of electrophilic attack on nitrogen, were observed only seldom, provided mild conditions were used. 

Heterocyclic amines are compounds that contain one or more nitrogen atoms as part of a ring. Saturated heterocyclic amines usually have the same chemistry as their open-chain analogs, but unsaturated heterocycles such as pyrrole, imidazole, pyridine, and pyrimidine are aromatic. All four are unusually stable, and all undergo aromatic substitution on reaction with electrophiles. Pyrrole is nonbasic because its nitrogen lone-pair electrons are part of the aromatic it system. Fused-ring heterocycles such as quinoline, isoquinoline, indole, and purine are also commonly found in biological molecules. 

Benzo[c]thiophene is a source of 3-substituted derivatives of 3,4-dihydro-1//-2-benzothiopyrans via ring opening to the dianion and subsequent reaction with electrophiles <96JOC1859>. 

A major advantage of the sequence presented here is that the aldehyde group is protected at the siloxycyclopropane stage, which allows convenient storage of this stable intermediate. Of equal importance is the valuable carbanion chemistry that can be carried out a to the ester function. Efficient substitution can be achieved by deprotonation with LDA and subsequent reaction with electrophiles.12-13-6 This process makes several a-substituted [1-formyl esters available. Other ring opening variants of siloxycyclopropanes - mostly as one-pot-procedures - are contained in Scheme I. They underscore the high versatility of these intermediates for the synthesis of valuable compounds.6 Chiral formyl esters (see Table, entries 2-5) are of special... 

One of the most efficient procedures for the synthesis of cyclopropanes is the reaction of alkenes with electrophilic carbene complexes. In this process up to three stereogenic centers can be generated in one step. Cyclopropanes are a key structural element encountered in many natural products with interesting biological activity. Further, by virtue of the ability of cyclopropanes to undergo ring-opening reactions these compounds can be valuable synthetic intermediates. 

Finally, the ring opening of substituted thioisocromans (402) with lithium and a catalytic amount of DTBB (5%) in THF at —78 °C gave the expected benzylic intermediates 403 which, after reaction with electrophiles at the same temperature and final hydrolysis with water, yielded functionalized thiols 404 (Scheme 113) . 

Upon warming, these oxazolinyl-stabilized lithiooxiranes undergo an electrocyclic a-ring opening to give a-oxo-2-oxazolines after hydrolysis (Scheme 87). However, all attempts to quench the presumed oxazolidine enolate intermediates through reaction with electrophiles failed. 

The regioselectivity of these ring opening reactions is sensitive to additional annelation on benzene (Table 7). In the tetralin derivative (59), little selectivity between type I and type II products is observed with either set of electrophilic reagents. A reversal of regioselectivity is observed in cyclobutabenzene and indan... 

The anomolous 4-substituted derivatives are observed only when aldehydes are employed as the electrophiles, but interestingly they are almost exclusively the sole products formed in this case. Their formation is believed to arise via reaction with the lithium enolate form of the ring-opened species, with subsequent enolization and ring closure giving rise to the observed products (Scheme 77)(9IJOC449). 

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