• Synthesis of bio-active natural products mainly involving radical chemistry. 
• Development of novel methodologies of synthetic significance.

Radical reactions has opened the door of a new era in recent years for carbon-carbon bond formation and it reflects its significance as a powerful tool in modern synthetic chemistry with high regio- and stereoselectivity. RajanBabu and Nugent have successfully developed the C-O homolytic cleavage of epoxides by bis(cyclopentadienyl) titanium(III) chloride [Cp₂TiCl] at room temperature and used the technology in organic synthesis. The reagent was easily generated in situ from inexpensive commercially available Cp₂TiCl₂ and activated zinc dust in THF.

2Cp₂TiCl₂  +  Zn  ®  2Cp₂TiCl  +  ZnCl₂

The discovery of this novel radical technology opened up a new valuable tool in synthetic organic chemistry throughout the world. Our research group contributed a considerable amount of work in this field for more than two decades or so. We have successfully achieved the stereoselective total synthesis of several anti-tumour antibiotics such as Methylenolactocin, Protolichesterinic acid, Dihydroprotolichesterinic acid and Roccellaric acid through radical cyclization of epoxides using titanocene(III) chloride (Cp₂TiCl) in racemic as well as in optically active forms.

This radical technology has also been applied for the total synthesis of various naturally occurring biologically active furano lignans such as Dihydrosesamin, Lariciresinol dimethyl ether, Acuminatin methyl ether, Sanshodiol methyl ether, Lariciresinol, Acuminatin, Lariciresinol monomethyl ether and furofuran lignans such as Sesamin, Eudesmin, Piperitol methyl ether, Pinoresinol, Piperitol, Pinoresinol monomethyl ether in racemic forms in a very concise and biogenetic pathway. Recently, we have also established their enentioselective synthesis through Sharpless kinetic resolution method. 

We have applied the radical method for the synthesis of naturally occurring hydrangenol, Phyllodulcin, Macrophyllol and Thumberginol G containing 3,4-dihydroisocoumarin moiety.

Encouraged by these successful applications of the radical cyclization strategy we have also completed very recently the asymmetric synthesis of fused bis-gamma-butyrolatones for the synthesis of bio-active molecules such as Canadensolides, Xylobovide etc. 

Baylis-Hillman adduct underwent smooth radical-induced condensation with activated bromo compounds and epoxides using titanocene(III) chloride (Cp₂TiCl) as the radical generator. The reactions of activated bromo compounds with 3-acetoxy-2-methylene alkanoates provided (E)-alkenes exclusively, whereas similar reactions with 3-acetoxy-2-methylene alkanenitriles led to (Z)-alkenes as the major product. The reactions of epoxides with Baylis-Hillman adduct furnished  alpha-methylene/arylidene-delta-lactones in good yield via addition followed by in situ lactonization.

We have also demonstrated a titanocene(III) chloride mediated radical induced mild and convenient allylation of aldimines and its application towards the synthesis of some important aza-sugar molecules and alkaloid skeletons.

Titanocene(III) chloride (Cp₂TiCl) mediated stereoselective synthesis of highly substituted tetrahydrofurans has been achieved using Baylis-Hillman adduct and activated bromo/iodo compounds via tandem radical cyclization reaction. The reaction of epoxide with Baylis-Hillman adduct furnished spiro-lactone via radical cyclization followed by in situ lactonization.

In continuation of our ongoing research on the total synthesis of natural products and related compounds through titanocene(III) chloride (Cp₂TiCl) mediated radical cyclization reactions, we describe herein the formal synthesis of magnofargesin and 7^'-epimagnofargesin in a concise and efficient route by opening of epoxides using Cp₂TiCl as the radical initiator.

We have successfully developed a simple and efficient Cp₂TiCl mediated radical induced synthetic protocol for the synthesis of benzylidene substituted tetrahydrofurans following the addition-elimination strategy. The technique has been applied to the total synthesis of a mixture of naturally occurring furano lignans, magnofargesin and its epimer 7´-epimagnofargesin, through addition-elimination process in optically active forms.

We have also applied this radical cyclization strategy for several organic transformations and methodologies such as (i) deoxygenation of alpha,beta-epoxyketones to enones (ii) synthesis of spirocyclic ethers (iii) allylation of aldehydes (iv) radical cyclization of alpha-bromo carbonyl compounds (v) conjugate addition of activated bromo compounds (vi) Wagner-Meerwein-type rearrangement of epoxides in camphoric systems (vii) synthesis of polysubstituted tetrahydropyrans and (viii) 8-endo radical cyclizations for synthesis of eight-membered cyclic ethers (ix) radical promoted cyclizations of aromatic carbonyl compounds to benzopyrans using titanocene(III) chloride (x) titanocene(III) chloride mediated radical-induced one pot synthesis of alpha-methylene-gamma-butyrolactones etc.

We have also developed several novel synthetic methodologies of synthetic importance i.e., (i) protection of alcohols by 3,4-dihydropyran (ii) chemoselective thioacetalisation (iii) regio and stereoselective formation of dihydrofurans by oxidative [3+2] cycloaddition of 1,3-diketones to cinnamic esters (iv) synthesis of fused acetals by cycloaddition of 1,3-dicarbonyl compounds to cyclic enol ethers (v) selective deprotection of tetrahydropyranyl ethers to alcohols (vi) selective cleavage of tert-butyldimethylsilyl ethers to alcohols (vii) selective cleavage of ketals and acetals (viii) selective bromoalkoxylation of activated cinnamyl compounds (ix) chemo and regioselective oxidative nuclear bromination of activated aromatic compounds (x) oxidative halodecarboxylation of a,b-unsaturated aromatic acids (xi) protection of carbonyl compounds as 1,3-oxathianes (xii) chemoselective synthesis of acylals from aldehydes and their deprotections (xiii) oxidative nuclear chlorination of activated aromatic compounds by acetyl chloride (xiv) protection of carbonyl compounds as oxathiolanes, dithiolanes and dithianes (xv) mild and efficient iodine catalyzed protection of carbonyl compounds as oxathiolane derivatives (xvi) mild and efficient a-chlorination of ketones by acetyl chloride (xvii) synthesis of b-keto enol ethers from b-diketones and their deprotection (xviii) synthesis of bis(indolyl)methanes in aqueous medium (xix) chemoselective deprotection of acetonides by using cheap and commercially available reagents such as ceric ammonium nitrate, lithium bromide, molybdenyl acetylacetonate etc.