Indole is one of the most important heterocycles widely present in bioactive natural products, pharmaceuticals, agrochemicals and materials. Being easily accessible, the 2-nitrostyrenes are attractive starting materials for the indole synthesis and the Cadogan-Sundberg reaction is one of the well-established methods exploiting the reductive cyclization of 2-nitrostyrene derivatives. The harsh reaction conditions associated with this named reaction [reflux in P(OEt)3] limited, nevertheless, its synthetic applications. Consequently, alternative conditions combining different transition metal catalysts with a terminal reductant have been developed. Recently, our group demonstrated that aqueous TiCl3 is a mild reductant capable of promoting the reductive cyclization of 2-nitrostyrene derivatives at room temperature leading to diversely substituted indoles or indolenines. The reaction was featured in the total synthesis of complex natural products such as (+)-1,2-dehydroaspidospermidine, (+)-condyfoline and (-)-tubifoline. This thesis focuses on the development of TiCl3-promoted reductive cyclization of previously unexploited substrates for the synthesis of important heterocycles and their applications in natural product synthesis. In chapter 2, we describe a novel synthesis of 3-acyloxy-2,3-disubstituted indolenines via TiCl3-mediated reductive cyclization of tetrasubstituted enol esters bearing a 2-nitrostyrene substituent. Mechanistically, a domino process involving a partial reduction of the nitro to nitroso group followed by a 5-center-6p-electrocyclization, 1,2-acyloxy migration and further reduction of the resulting nitrone intermediate accounts for the reaction outcome. This operationally simple reaction (aqueous TiCl3 solution, MeCN, 0 °C to room temperature) tolerates a wide range of functional groups affording 3-acyloxy-2,3-disubstituted indolenines in good to high yields. Conceptually, this important heterocycle is accessed for the first time under reductive conditions. Chapter 3 details our approach towards the total synthesis of trigonoliimine C, a pentacyclic bisindole alkaloid, featuring the reductive cyclization of enol esters as a key step. The requisite enol ester was synthesized via following a two steps procedure: a) Ketone synthesis via the Liebeskind-Srogl coupling; b) Enol ester formation by treatment of the ketone with LiHMDS at -78 °C followed by addition of Ts2O. However, all attempts to generate the 3-acyloxy-2,3-disubstituted indolenines met with failure at the present stage of development. Benzofuro[3,2-b]indoline is a key structural motif found in phalarine. It is synthetically much more difficult to access than its isomer, the benzofuro[2,3-b]indoline. The few existing methods suffer from the low regioselectivity in the oxidative coupling of two selected building blocks. We describe in Chapter 4 a TiCl3-mediated reductive cyclization of tetrasubstituted alkenes bearing a 2-nitrophenyl substituent and a properly tethered nucleophile. The starting materials were prepared via a key Suzuki-Miyaura cross couping of tosyl enol ester with aryl boronic acid based on Gosselin's report. Treatment of a MeCN solution of tetrasubstituted alkenes with aqueous TiCl3 and NH4OAc afforded the desired (benzo)furo[3,2-b]indolines in good to high yield with excellent regioselectivities. Total synthesis of phalarine featuring this novel reductive cyclization methodology was exploited and is being pursued in our laboratory.