Cyclopropane derivatives cyclization

In the reaction with epoxides, y-hydroxysulfones are obtained278-280. For example, Kondo and coworkers279 synthesized various (5-lactols 226 by treating sulfone acetals 225 with terminal epoxides as shown below. Dilithiated phenylsulfonylmethylene reacted with haloepoxide and afforded 3-(phenylsulfonyl)cycloalkanols281. Treatment of y, 5-epoxysulfones 227 and 229 with n-butyllithium resulted in cyclization to form cyclopropane derivatives 228 and bicyclobutane 230, respectively282. 

Treatment of a-lithionitriles with vinylic sulfones resulted in the formation of cyclized products, i.e., 3-oxothian-l, 1-dioxides 346 or cyclopropane derivatives 348. When a-lithiated aliphatic nitriles were used, carbanions 343, formed by the nucleophilic addition,... 

Cyclopropyl sulfones were shown to be obtained either by cyclization of y-p-tosyloxy sulfones 232 with base or by treatment of phenylsulfonylacetonitrile 233a or ethyl phenyl sulfonyl acetate 233b with 1,2-dibromoethane in the presence of benzyltriethyl-ammonium chloride (BTEA) and alkali in good yields. Chang and Pinnick synthesized various cyclopropane derivatives 234 upon initial treatment of carbanions derived from cyclopropyl phenyl sulfone with either alkylating agents or a carbonyl compound and subsequent desulfonylation, as shown below. 

Concerning the structure, the cyclopropane derivatives 524—526 deviate from the generally observed cycloadducts of cyclic allenes with monoalkenes (see Scheme 6.97 and many examples in Section 6.3). The difference is caused by the different properties of the diradical intermediates that are most likely to result in the first reaction step. In most cases, the allene subunit is converted in that step into an allyl radical moiety that can cyclize only to give a methylenecyclobutane derivative. However, 5 is converted to a tropenyl-radical entity, which can collapse with the radical center of the side-chain to give a methylenecyclobutane or a cyclopropane derivative. Of these alternatives, the formation of the three-membered ring is kinetically favored and hence 524—526 are the products. The structural relationship between both possible product types is made clear in Scheme 6.107 by the example of the reaction between 5 and styrene. 

HCCl2C00Me could be used instead of CHCI3 with similar results [128]. For (43a), cyclization by intramolecular Sn2 reaction competes with protonation, and when stoichiometric amounts of EGB and CHCI3 were used, the cyclopropane derivative was the main product. Scheme 32, since protonation of the intermediate anion now has to be from (33H), which is less acidic than CHCI3 [128],... 

C1CH2CH2CHZ [Z = C(0)H, CCH, or CN] to cyclopropane derivatives. In each case the cyclization barrier is lower than the 5n2 barrier of an analogous acyclic system, despite the cyclization being over 25kcal moP less exothermic. The surprisingly small enthalpic barrier to the cyclizations is due to the nucleophile being held in close proximity to the electrophilic site in the substrate, and this destabilizes the ground state. 

In qualitative terms, the rearrangement reaction is considerably more efficient for the oxime acetate 107b than for the oxime ether 107a. As a result, the photochemical reactivity of the oxime acetates 109 and 110 was probed. Irradiation of 109 for 3 hr, under the same conditions used for 107, affords the cyclopropane 111 (25%) as a 1 2 mixture of Z.E isomers. Likewise, DCA-sensitized irradiation of 110 for 1 hr yields the cyclopropane derivative 112 (16%) and the dihydroisoxazole 113 (18%). It is unclear at this point how 113 arises in the SET-sensitized reaction of 110. However, this cyclization process is similar to that observed in our studies of the DCA-sensitized reaction of the 7,8-unsaturated oximes 114, which affords the 5,6-dihydro-4//-l,2-oxazines 115 [68]. A possible mechanism to justify the formation of 113 could involve intramolecular electrophilic addition to the alkene unit in 116 of the oxygen from the oxime localized radical-cation, followed by transfer of an acyl cation to any of the radical-anions present in the reaction medium. 

In a similar manner, A-Cbz-a-Lys-OMe reacted with an electrophilic cyclopropane derivative, and a mixture of diastereomeric y-lactams was isolated. The reaction is postulated to proceed by an attack of the amino group on the methylene group with subsequent cyclization (Scheme 4) (85JOC3631). 

The imine 26 shows a similar behavior (90CB1161). In this case, too, the reaction products (2,3-dimethyl-2-butene and methyl isocyanide) are the expected thermolysis products of a cyclopropane derivative, and it is therefore safe to postulate the latter as the ring contraction product that is formed by cyclization of an intermediate diradical evolving from 26. 

Enolates with a leaving group in the y position can cyclize to yield cyclopropanes instead of reacting intermolecularly with an electrophile. 3-Halopropy] ketones or 4-halobutyric acid esters, for instance, are readily converted to cyclopropane derivatives when treated with a base (Scheme 5.64 see also Section9.4.1). 

The reaction of 5-silyl-y,5-epoxypentanenitrile derivatives with a base and an alkylating agent gives (Z) - 3 - s i I o x y- y, 3 -u n saturated pentanenitrile derivatives via a tandem process that involves the formation of a cyclopropane derivative by epoxy nitrile cyclization followed by Brook rearrangement and an anion-induced cleavage of the cyclopropane ring (Scheme 105).152... 

To examine the viability of CIM a number of photoreactions (electrocyclic reactions, Zimmerman (di-n) reaction, oxa-di-7i-methane rearrangement, Yang cyclization, geometric isomerization of 1,2-diphenyl-cyclopropane derivatives, and Schenk-ene reaction) which yield racemic products even in presence of chiral inductors in solution have been explored (Sch. 40) [187,189-200]. Highly encouraging enantiomeric excesses (ee) on two photoreactions within NaY have been obtained photocyclization of tropolone ethylphenyl ether (Eq. (1), Sch. 40) and Yang cyclization of phenyl benzonorbornyl ketone (Eq. (3), Sch. 40). The ability of zeolites to drive a photoreaction that gives racemic products in solution to ee >60% provides... 

In analogy to the preparation of the cyclopropanone hemiacetal 3 (vide supra, Eq. (1)7), reductive cyclization of the piperidide of 3-chloropropionic acid 193 with sodium in ether in the presence of ClSiMe3, gave the 1-piperidino-l-trimethylsilyloxy-cyclopropane 194 a which was converted to the cyclopropanol 194 b upon treatment with methanolic tetrabutylammonium fluoride. Both 194 a and 194 b can be used for the ready generation of cyclopropane derivatives thus the silyl ether 194a could be reacted directly with the vinylic Grignard reagents 195 to provide the vinyl cyclopropane derivative 196, (Eq. (61)128). 

An interesting carbocyclization process was observed when alkenyl stannanes were treated with electrophilic selenenylating reagents containing a non-nucleo-philic counterion. Thus, Nicolaou showed that compound 213 reacted with AT-PSP 11 to form the intermediate 214 which then afforded the cyclopropane derivative 215 (Scheme 32) [109]. Further examples were reported by Herndon [110]. As indicated in Scheme 32, in the presence of tin tetrachloride, the stannane 216 was converted into the cyclopentane derivative 217. This cyclization reaction proved to be quite general with respect to a variety of substitution patterns but it appears to be restricted to the formation of three- and five-membered ring. 

As discussed in Sect. 2, a-selanylalkyllithiums, generated from selenoacetals, can react with various electrophilic reagents, i. e. chloromethyl isopropyl ether for the synthesis of la-hydroxy vitamin D analogues [25] and with propargylic chloride derivatives for the preparation of alkynols [26]. A synthesis of vinyl-cyclopropane derivatives from l,4-dichloro-but-2-ene was achieved with trans stereoselectivity (>93%) in 68-89% yield. This one-pot cyclization, via an intramolecular allylic substitution, required the presence of two equivalents of u-BuLi [26] (Scheme 23). 

Irradiation of the E-isomer of (70) brought about E-Z isomerization as well as cyclization by group migration to the cyclopropane derivatives (71). These derivatives were also photoreactive and ring-opened to the alkenes (72). The kinetics of the photorearrangement of the benzocycloheptene (73) has been studied in detail. Irradiation in methanol affords the six products shown in Scheme 5, and solvent dependence in the reaction was investigated. 

The original approach was designed to emulate the successful cyclization of anion V to the sativene precursor VI, by means of base treatment of a closely related enone derivative. The resulting anion (Vila) from the enone, however, failed to cyclize as predicted, yielding only the cyclopropane derivative I (see Scheme 6.2). The end result was, nevertheless, equally rewarding, since structure III exactly filled the purpose for which anion Vllb was intended. 

Haloalkyl phenyl sulfides produce cycloalkyl phenyl sulfides on treatment with base. The synthesis of cyclopropyl phenyl sulfides has attracted particular interest since these compounds can be metal-lated - - by Bu"Li in THF and the resulting 1-phenylthiocyclopropyllithium has been used for spiro-annelation of various cycloalkanones. - Thus, 3-chloro-l-phenylthiopropane leads to phenylthiocyclopropane on reaction with potassium amide in liquid ammonia (Scheme 7, entry a), but attempts to prepare 2-methylcyclopropyl phenyl sulfide from 3-chloro-l-phenylthiobutane by an analogous route failed in the cyclization step. Neither 3-mesyloxy- and 3-tosyloxy-l-phenylthiododecanes " nor 3-tosyloxy-l-phenylthiobutane produce cyclopropane derivatives either on reaction with LDA in THF (Scheme 7, entry b). Failure in these ring closure reactions has been attributed to inadequate car-... 

Cyclization. Treatment of a l-al-4-ene system (1) with the rhodium complex (1 eq.) in chloroform, benzene, or acetonitrile at room temperature yields a 2,3-dialkyl cyclopentanone (2) and a cyclopropane derivative (3) formed by decarbonylation. The... 

---