Tributylstannyl indoles

Beccalli et al. reported a new synthesis of staurosporinone (293) from 3-cyano-3-(lH-indol-3-yl)-2-oxo propionic acid ethyl ester (1464) (790). The reaction of 1464 with ethyl chlorocarbonate and triethylamine afforded the compound 1465, which, on treatment with dimethylamine, led to the corresponding hydroxy derivative 1466. The triflate 1467 was prepared from 1466 by reaction with trifluoromethanesulfonic anhydride (Tf20) in the presence of ethyldiisopropylamine. The palladium(O)-catalyzed cross-coupling of the triflate 1467 with the 3-(tributylstannyl)indole 1468 afforded the vinylindole 1469 in 89% yield. Deprotection of both nitrogen atoms with sodium ethoxide in ethanol to 1470, followed by photocyclization in the presence of iodine as the oxidizing agent provided the indolocarbazole 1471. Finally, reductive cyclization of 1471 with sodium borohydride-cobaltous chloride led to staurosporinone (293) in 40% yield (790) (Scheme 5.248). 

The formation of seven membered heterocycles and larger rings through cross-coupling reactions is quite rare (except for some macrocyclic natural products). An example of such a process is presented in 5.1. The intramolecular Stille-coupling of the tributylstannyl-indole and vinyl bromide moieties led to the formation of a seven membered ring in good yield.1... 

Hudkins et al. prepared a new reagent, l-carboxy-2-(tributylstannyl)indole (126), using COj to introduce an amine-protecting group [118], The Stille coupling of 126 with... 

The indolyltributylstannanes, which are more robust than their trimethylstannyl counterparts, are prepared similarly [166, 167]. Labadie and Teng synthesized the IV-Me, N-Boc, and jV-SEM (indol-2-yl)tributylstannanes [167], and Beak prepared the A-Boc trimethyl- and tributyltin derivatives in high yield [166]. Caddick and Joshi found that tributylstannyl radical reacts with 2-tosylindoles to give the corresponding indole tin compounds as illustrated [168]. 

Many pyridine-indole compounds are biologically active. A growing number of methods for the preparation of indolylstannanes have been developed. 2-Trialkylstannylindoles, for example, have been synthesized via directed metalation followed by reaction with tin chloride [91-93]. The latest indolylstannane syntheses include Fukuyama s free radical approach to 2-trialkylstannylindoles from novel isonitrile-alkenes [94], and its extension to an isonitrile-alkyne cascade [95]. Assisted by the chelating effect of the SEM group oxygen atom, direct metalation of 1-SEM-indole and transmetalation with BujSnCl afforded 2-(tributylstannyl)-l//-indole 108, which was then coupled with 2,6-dibromopyridine to give adduct 109. 

An excellent example of the formation of a six membered ring is the hexabutyldistannane mediated ring closure of the brominated indole derivative shown in 4.1. The first step of the process is the palladium catalyzed exchange of one of the bromines to a tributylstannyl moiety, followed by the closure of the six membered ring in a Stille coupling.1... 

Tokuyama et al. designed a highly elegant synthesis of indoles by reacting tributylstannyl radicals or hypophosphite salts with imsaturated... 

Lilly chemists prepared 998b as part of a series of 4-amino-6-heteroaryl-l,3,4,5-tetrahydrobenz[c,d]indoles evaluated as anti-emetic agents via coupling of 2-(tributylstannyl)oxazole 996 with (+)- 2aR, 45)-l-benzoyl-6-iodo-4-(di-n-pro-pylamino)-l,2,2a,3,4,5-hexahydrobenz[c,d]indole 997. They isolated 998b after deprotection as shown in Scheme 1.266. 

Fukuyama devised a novel tin-mediated indole ring synthesis leading directly to 2-stannylindoles that can capture aryl and alkyl halides in a Pd-catalyzed crosscoupling termination reaction [110-112]. The presumed pathway is illustrated and involves initial tributylstannyl radical addition to the isonitrile 65, cyclization, and final formation of stannylindole 66. 

A tandem radical sequence was observed when the indole amide 120 was treated with tributylstannyl radical [81]. The initially formed aryl radical is proposed to undergo a 1,5-hydrogen atom abstraction to form an a-amido radical en route to the cyano spiroindolines 121a and 121b. Treatment with potassium tert-butoxide and oxygen in THF gave the C-3 spirooxindole in modest yield. 

---