6- endo-dig

Rule 3. For digonal reaction sites (e.g. nucleophilic attacks at triple bonds), 5- to 7-exo-dig and 3- to 7-endo-dig are favored whereas 3- to 4-exo-dig reactions are disfavored. 

Joshi et al. have reported a diastereospecific synthesis of pentacyclic /3-lactams by 6-exo-trig/7-endo-dig tandem radical cyclization [33]. On the occasion of the total synthesis of new sargine-type alkaloids, Takayama et al. have disclosed a formation of pentacyclic derivatives from a tryptophan derivative [34]. 

We have also achieved imusual 7-endo-dig and 7-endo-trig radical cyclizations employing the MesSiCl/col combination as titanocene-regenerating agent [69]. Moreover, we have provided theoretical and experimental evi-... 

Cyclization (7-endo-dig) of the enyne (598) to the enedione (599) followed by conversion into damsinic acid (600) represents a new synthetic route to the pseudoguaianolide framework (Scheme 64). It has also been proposed " that... 

Another very short route to racemic olean comes from Jef De Brabander, and is based on the platinum-catalysed intramolecular hydroalkoxylation of internal alkynes. Under optimised conditions, the 6-exo-dig/7-endo-dig ratio is more than 100 1. [218]... 

When the core chromophore is changed to pyrazine (Scheme 30.23, bottom), interaction of enediyne moiety with 1,4-cyclohexadiene proceeds as a cycloaddition [40]. The latter change in reactivity is attributed to the particularly fast formation of an electrophilic triplet state that attacks the jc-bond of 1,4-CHD. In the presence of an ortho-amide functionahty, the same chromophore undergoes either a 7-endo-dig cyclization or photohydration [41]. 

A Pt-catalyzed intramolecular aryl C(sp )-H functionalization was developed by Seller and coworkers with pyrrole-2-carboxamide alkyne 141 in the presence of H2PtClg 6H2O, which was applied to construct poly-Af-heterocycles (Scheme 12.62) [66]. Pyrrolo[3,2-c]azepin-4-one derivatives 142 were obtained in moderate to good yields. Interestingly, this 7-endo-dig cyclization process involved a concomitant rearrangement of the amidocarbonyl group from the 2-to the 3-position of the pyrrole ring. 

Ramana CV, Induvadana B, Srinivas B, Yadagiri K, Deshmukh MN, Gonnade RG (2009) The influence of electronic factors on Pd-mediated cycloisomerizatioma systematic investigation of competitive 6-exo-dig versus 7-endo-dig cyclizations of sugar alkynols. Tetrahedron 65 9819-9832... 

It might, at first glance, come as a surprise that, despite the ban on 5-endo-trig cyclizations, 5-endo-dig cyclizations are allowed. A possible reason for this observation is that intramolecular nucleophilic or electrophilic attack at an alkyne can proceed with the substrate in a flat conformation, because two orthogonal jt (or jt) orbitals are available. Similarly, hydroxymethyl allenes cyclize on treatment with a base (Scheme 9.7), because the terminal Jt orbital of the allene and the hydroxymethyl group can readily achieve a synperiplanar orientation. Intramolecular... 

Scheme9.7. Examples of 5-endo-dig cyclizations [1 7-21] and 5-endo-trig cyclizations of allenes [22],...

Alkyl and aryl substitution of the alkyne is tolerated for the iridium(m) hydride 139 mediated (>-endo-dig cyclization of 2-alkynylbenzyl alcohols to form 1/7-isochromenes (Equation 67) <2005OL5437>. 

A variety of electrophilic reagents can induce a k-endo-dig lactonization of (Z)-2-en-4-ynoates to afford 2//-pyran-2-ones with concomitant incorporation of the electrophile onto C-5 (Equation 253) <2003JOC5936>. However, formation of 5-methylenefuran-2(5/7)-ones, via an alternate 5-exo-dig lactonization, lowers the yield of the desired 27/-pyran-2-ones <2003JOC5936>. 

Baldwin has formulated rules for ring closure in a systematic manner . For digonal systems these are (/) 3- and 4-exo-dig, disfavoured ( ) 5- to 1-exo-dig, favoured (i/7) 3 to 1-endo-dig, favoured. In his terminology the choice in equation (58) is between S-exo-dig di di 6-endo-dig. On the basis of his survey Baldwin concludes that enrfo-ring closures at digonal carbon predominate. For the possibilities we encountered most often, namely, 5- to 7-rlngs, we find that first-row nucleophilic sites, e.g. O, N, C, favour 5-exo-dig and 6-exo-dig closures. These will be illustrated here and in later sections. 

Scheme 7-22 5-endo-dig Carbocyclization from a chiral ynol ether. 

Figure 10.7 (a) Loss of a stabilizing stereoelectronic effect (i.e. benzylic stabilization of the vinyl radical) imposes additional penalty on the 5-endo-dig cyclization. (b) The penalty can be removed via conformational constraints in the reactant. 

A further example for a metal-initiated reaction sequence providing an indole-inspired NP-based complex scaffold was reported by Van der Eycken and coworkers [7]. In this case, a Ugi reaction provided the desired substrate for the sequence of cyclization reactions initiated by the activation of the acetylene with a gold catalyst. The Ugi four-component reaction employed the indole-carboxaldehyde 12, the nitrile 13, amine 14, and carboxyhc acid 15 and led to the formation of the intermediate 16. In the presence of a gold(I) catalyst, instead of the expected indoloazepinone that could be formed via an endo-dig cyclization, a tetracyclic spiroindoline 17 was formed diastereoselectively (Scheme 13.3). 

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