Intramolecular tandem 1,5-hydride

A Sc(OTf)3-catalysed intramolecular tandem 1,5-hydride transfer/cyclization process has been reported to construct 3-amino-3-carboxy-tetrahydroquinolines (Scheme 67). 0... 

An efficient FeCl3-catalysed stereoselective intramolecular tandem 1,5-hydride transfer/ring-closure reaction of benzylideneindolinones to give spirooxindole 0 tetrahydroquinolines has been reported (Scheme 64)7 ... 

The radical produced from the oxidative decarboxylation may also be trapped intramolecularly to form five- and six-membered rings (Scheme 17). The Kolbe protocol avoids the use of the toxic organ-otin reagents that are commonly used in the formation of radicals. Moreover, when alkyltin hydride reagents are used, a C—H bond is formed. The Kolbe reaction protocol, on the other hand, allows the radical formed after cyclization to be captured by a different radical in a coelectrolysis experiment, rather than being reduced. This tandem sequence of events has been exploited in the construction of prostaglandin precursor (70) [37-41]. Here, the cyclized... 

A tandem 1,4-addition-Meerwein-Ponndorf-Verley (MPV) reduction allows the reduction of a, /i-unsaturated ketones with excellent ee and in good yield using a camphor-based thiol as reductant.274 The 1,4-addition is reversible and the high ee stems from the subsequent 1,7-hydride shift the overall process is thus one of dynamic kinetic resolution. A crossover experiment demonstrated that the shift is intramolecular. Subsequent reductive desulfurization yielded fiilly saturated compounds in an impressive overall asymmetric reductive technique with apparently wide general applicability. 

Beckwith and Storey have developed a tandem translocation and homolytic aromatic substitution sequence en route to spiro-oxindoles [95CC977]. Treatment of the bromoaniline derivative 122 with tin hydride at 160 °C generated the aryl radical 123 which underwent a 1,5-hydrogen atom transfer to give intermediate 124. Intramolecular homolytic aromatic substitution and aromatization gave the spiro-oxindole 125. Intramolecular aryl radical cyclization on to a pyrrole nucleus has been used to prepare spirocyclic heterocycles [95TL6743]. 

Acyl radicals are very useful synthetic intermediates. Their preparation is not simple since the corresponding halides are highly electrophilic and cannot be used as radical precursors. Organocobalt compounds were proposed as suitable source of acyl radicals [44]. However, the use of acyl selenides proved to be more general [45, 46]. These radical precursors can be efficiently prepared from the corresponding carboxylic acids and esters [47]. Acyl phenyl selenides should be preferred, when possible, relative to acyl methyl selenides due to the consumption of two equivalents of tin hydride with this last system (Scheme 1) [4]. Acyl selenides have found many applications in tandem radical additions to alkenes. Examples of intermole-cular [Eq. (18)] [48,49] and intramolecular reactions [Eq. (19)] [50a] are reported. The enoyl selenide 68 give the unsaturated acyl radicals 69. This intermediate... 

Scandium triflate catalyzed the intramolecular redox reaction from yne-enones to ring-fused tetrahydroquinolines (eq 28). This Lewis acid-catalyzed intramolecular redox domino reaction occurs via domino 1,5-hydride shift and cycUzation to afford tetrahydroquinolines in moderate to excellent yields and with high diastereoselectivity. A similar Sc(OTf)3-catalyzed tandem 1,5-hydride transfer cyclization process was applied in the construction of 3-amino-3-carboxy-tetrahydroquinoline derivatives (eq 29). ... 

The reaction between ethyl Hthiopropiolate and the N-acylpyridinium salt formed by reaction of 4-methoxy-3-methyl-5-(triisopropylsilyl)pyridine 2363 with (+)-frafis-2-(a-cumyl)-cyclohexyl chloroformate (TCC chloro-formate) was the starting point in the synthesis of (-l-)-aUopumihotoxin 267A (1718) by Comins et al. (Scheme 301). The dihydropyridone product (—)- 2364 was obtained diastereoselectively (>96%) before hydrogenation to the saturated ester (+)-2365. However, some epimerization of the methyl substituent was apparent after cleavage of the TCC carbamate with lithium methoxide and cyclization to the indolizidinone (—)-2366 (dr 8 1). Acetoxylation at C-8 with lead tetraacetate was stereoselective, and introduced the acetate from the axial direction, possibly by stereoelec-tronicaUy-controUed intramolecular transfer of acetate from a lead—enol intermediate. The acetoxy product (—)-2367 was protodesilylated with formic acid, after which a one-pot tandem reduction with K-Selectride followed by hthium aluminum hydride gave diol (- -)-2368 with complete... 

The rapid development of organocatalysis impels chemists to discover new synthetic methodologies. Many important transformations that could only be realized by transition metal catalysis can now be achieved via organocatalysis. In 2010, Kim and coworkers reported a novel C-H bond functionalization reaction via a tandem 1,5-hydride transfer/ring closure sequence. Based on the iminium-enamine cascade activation of catalyst 33, the fused tetrahydroquino-Unes 35 could be synthesized from substrates 34 with good stereoselectivity. This is the first example of an organocatalytic intramolecular redox reaction (Scheme 36.10) [16]. 

Intramolecular oxo- or aminopaUadation provides an eflFicient tool for the preparation of various heterocyclic derivatives in recent years. In 2010, Alvarez et al. reported an effcient palladium-catalyzed tandem intramolecular oxopalladation/oxidative Heck coupling reaction toward benzofuians 196 [77] (Scheme 6.54). Nucleophilic attack of the oxygen to the activated carbon-carbon triple bond furnishes vinylpal-ladium intermediate 197, followed by alkene insertion into the C-Pd bond to afford alkylpalladium intermediate 198. The final product was generated via P-hydride elimination of intermediate 198. 

Remarkably, only a small number of intramolecular reactions utilize Barton esters " - likewise, the use of the Barton chemistry in making CC bonds in tandem or domino reactions is far less exploited compared to the tin-hydride-mediated free-radical sequences. The following example is taken from the biomimetic conversion of isoflavone to the rotenoid, where the reaction affords the 6-endo product (Scheme 24). ... 

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