MIRC

More recently, Tardella and co-workers reported that treatment of 2-trifluorome-thyl acrylate 36 (Scheme 3.12) with the anion generated from nosyloxycarbamate 37 gave rise to aziridine-2-carboxylate 38 in 96% yield and 72% de with undetermined stereochemistry [40]. Aza-MIRC (Michael-initiated ring closure) was used to account for this transformation. A number of other hydroxylamine derivatives have been employed successfully in this type of aziridination reaction, includ-... 

An indirect nucleophilic opening is depicted in Scheme 24. The functionalized vinyl aziridine 37 undergoes a Michael-initiated ring closure (MIRC) reaction upon treatment with suitable nucleophiles to give cyclopropanes with concomitant opening of the aziridine ring [34]. 

The optimum results were obtained with Grignard reagents in the presence of 10 mol % of Cu(I)CN. The stereochemical course of this MIRC reaction can be explained by adopting Yamamoto s model for conjugate addition of cyano-cuprates to y-alkoxy-a,)5-unsaturated esters (Fig. 2) [35]. In this model, it is proposed that the larger substituent (L), in our case the tosyl group, will adopt the... 

The cz5-aziridine substrate shows, as expected on the basis of this model, predominant formation of the trans-cyclopropane product. The starting materials for this MIRC reaction can readily be obtained from the aziridine esters by reduction to the corresponding aldehyde and a subsequent Knoevenagel reaction with malonate ester (Scheme 25) [34]. 

Bond constructions similar to those just discussed can be achieved using an alkylidene malonate which is tethered to an alkyl bromide [72]. Of particular interest in this context is the controlled potential reductive cyclization of 263. As illustrated, the method provides a reasonably facile and modestly efficient entry to cyclobutanes 264. Presumably, the process is initiated by reduction of the alkylidene malonate rather than the alkyl halide, since alkyl bromides are more difficult to reduce. The same substrate, when reduced with L-Selectride undergoes conjugate addition of hydride and a subsequent cyclization leading to the five-membered ring 265. The latter transformation constitutes an example of a MIRC reaction [71-73], a process which is clearly complementary to the... 

MIRC and MIMIRC Reactions Leading to Spiropentanes, Tricyclo[3.2.1.0 ]octanes and Other Tricyclic Skeletons... 

The Michael addition followed by Intramolecular Ring Closure (MIRC) reactions have been recognized as a general synthetic approach to carbocyclic three-membered ring derivatives [1]. The enhanced Michael reactivity of methyl 2-chloro-2-cyclopropylideneacetate (1-Me) towards thiolates, alkoxides, lithiated amides and cyclohexadienolates (see below) allows one to perform highly efficient assemblies of spiropentane, tricyclo [3.2.1.0 ]octane, bicyclo [2.2.2] octane... 

Scheme 62. Two MIRC reactions of methyl 2-chloro-2-cyclopropylideneacetate (1-Me) [104]...

From a formal point of view, the one-pot heterocyclizations discussed in Sect. 4.2 may be also called MIRC reactions, in the present section this term implies the formation of a cyclopropane ring in accordance with the generally accepted MIRC mechanism [1]... 

Cyclopropane ring formation has been brought about by Michael addition initiated ring closure (sometimes called MIRC). The reaction of methyl 4-bromocrotonate (3) with different nucleophiles either gives the SN2-displacement product 4 or the Michael addition intermediate 5 which finally forms the cyclopropane carboxylate 697 (the configuration of 6 has not been determined). This reaction has been studied with different nucleophiles in the solvent systems tetrahydrofuran-HMPA (20 1) and tetrahydrofuran the bromocrotonate 3 was reacted with 1 equivalent of a 1 M solution of the lithium enolates at —78 for 12 h at room temperature97. 

In addition, we were able to extend the tandem hetero Michael addition/a-ester-enolate alkylation protocol by an intramolecular variant via a Michael-initiated ring closure (MIRC) reaction leading to diastereo- and enantiomerically pure trans-configured 2-amino-cycloalkanoic acids 30 (Scheme 1.1.7) [14c,d]. 

Similarly, organolithiums (or Grignard reagents) add to ester (26) to afford silyl enolates which are intercepted with aldehydes and ketones to give a,p-unsaturated esters (27),434 while addition of the bifunctional aryllithium (28) (MIRC protocol) affords the 2-(trimethylsilyl)tetrahydronaphthoate ester (29 Scheme 7).43b... 

Esters are far less reactive as electrophiles when compared to aldehydes and ketones. Successful tandem vicinal dialkylations are possible using alkyl formates,67 but most esters lack the needed reactivity. More reactive thioesters can serve as electrophiles in these sequences.208 Presence of a potentially electrophilic ester group as a substituent in the conjugate enolate permits very efficient Dieckmann cycliza-tion to take place as the second step of a MIRC sequence (e.g. equations 5118 and 52).24 Ortho esters are far more reactive, giving p-keto esters as adducts when used in sequences that employ enones as substrates.230... 

A sugar-derived vinyl sulfone (92) was found to undergo a Michael-initiated ring closure (MIRC) process to build up a chiral polysubstituted oxolan system with high stereoselectivity, yielding the all-syn stereoisomer (93) (Scheme 25).61 The observed MIRC selectivity demonstrates that the 5-exo-trig process is strongly... 

An interesting feature of Michael addition reactions is that Michael acceptors with a leaving group (mostly halides) in y-position can be used for the synthesis of cyclopropanes. The so-called Michael-initiated ring closure reaction (MIRC reaction) starts with an addition of a nucleophile to the a,/3-unsaturated carbonyl, and afterwards the intermediate enolate displaces the leaving group to give the desired cyclopropanes. ... 

Rearrangements of complex aziridines can also result in interesting cyclic structures. For example, Zwanenburg and co-workers <1996T12253> have applied the Michael reaction-induced ring-closure (MIRC) reaction to aziridinyl... 

The utility of the SAMP/RAMP hydrazone method in diastereo- and enantioselective Michael additions was demonstrated in the synthesis of 5-oxo esters " (eq 9), -lactones (eq 10), 0x0 diesters and dinitriles, heterocyclic compounds (eq 11), MIRC (Michael initiated ring closure) reactions, and 2-substituted 4-oxo sulfones. ... 

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