He has contributed extensively to the synthesis of β-lactams using alkenyl anions, ynolates, novel isocyanates, iron vinylidines, heteroatom functionalized nitroalkenes, and ring closing alkene and enyne metathesis reactions.

He has also published highly flexible methods for the biomimetic total syntheses of resorcylate and meroterpenoid natural products including 15G256β,[6] aigialomycin D,[7] LL-Z1640-2,[8] cruentaren A,[9] hericenone J[10] and macrosporin,[11] amorphastilbol,[12] (+)-hongoquercin A and B,[13] and austalides.

[14] Barrett, in collaboration with Brian M. Hoffman at Northwestern University, has published pioneering work on the synthesis of diverse porphyrazines bearing 8, 6, 4, and 2 thiols, amines or alcohols as peripheral macrocyclic ring substituents and the conversion of these polydentate ligands by the complexation of metal ions both within the macrocyclic cavity and at the periphery to produce diverse multimetallic complexes.

[17][18][19][20] Additionally, Barrett in collaboration with Simak Ali and R. Charles Coombes in Medicine at Imperial College and Dennis Liotta and James P. Snyder in Emory University has made pioneering contributions to addressing unmet medical need with the invention of highly selective and bioavailable inhibitors of the Cyclin Dependent Kinases including CDK-7 inhibitor ICEC0942 (CT7001), which have been licensed by Carrick Therapeutics for clinical trials to treat Tamoxifen-resistant and other cancers.

[21][22][23] Barrett was the first to demonstrate the increased stability of per-alkylated aza crown ether analogues under dissolving metal reduction conditions.