Lithiation–borylation is an invaluable carbon-carbon bond forming technique, which has been both pioneered and used extensively within our group to homologate organoboron species in high yields with excellent stereocontrol. This technique has allowed us to access to a wide-range of complex 3D structures that were previously inaccessible by traditional synthetic means [1-4].
The versatility of organoboron chemistry allows for the homologated organoboron species to be utilised in a number of ways, a prominent example of this is in Assembly-Line Synthesis. This is where up to 4 consecutive lithiation–borylation reactions can be carried out iteratively with exquisite 3D control to produce multiple contiguous stereogenic centres before a single aqueous work-up is required [5, 6].
Assembly-Line Synthesis mimics the way that complex natural products are biosynthesised in nature by essentially “growing” molecules with total control over their 3D shape [5, 6]. This has been demonstrated well within the context of total synthesis, where our group has quickly produced a number of synthetically challenging 3D structures [6, 7].
 Leonori, D., Aggarwal, V. K., Acc. Chem. Res., 2014, 47, 3174–3183 doi
 Essafi, S., Tomasi, S., Aggarwal, V. K., Harvey, J. N., J. Org. Chem., 2014, 79, 12148 − 12158 doi
 Fawcett, A., Nitsch, D., Ali, M., Bateman, J. M., Myers, E. L., Aggarwal, V. K., Angew. Chem. Int. Ed., 2016, 55, 14663–14667 doi
 Varela, A., Garve, L. K. B., Leonori, D., Aggarwal, V. K., Angew. Chem. Int. Ed., 2017, 56, 2127–2131 doi
 Burns, M., Essafi, S., Bame, J. R., Bull, S. P., Webster, M. P., Balieu, S., Dale, J. W., Butts, C. P., Harvey, J. N., Aggarwal, V. K., Nature, 2014, 513, 183–188 doi
 Balieu, S., Hallett, G. E., Burns, M., Bootwicha, T., Studley, J., Aggarwal, V. K., J. Am. Chem. Soc., 2015, 137, 4398–4403 doi
 Noble, A., Roesner, S., Aggarwal, V. K., Angew. Chem. Int. Ed., 2016, 55, 15920–15924 doi
Cross-coupling reactions account for the formation of over 60% of C-C bonds in the pharmaceutical industry. However, traditional cross-coupling reactions often rely heavily on the use of expensive or toxic transition-metal catalysts. As such, there is significant interest in developing more efficient transition-metal free methods.
Recently, our group has successfully developed new methodology towards transition-metal free cross-coupling reactions based upon our lithiation-borylation chemistry. The methodology allows for the reliable enantiospecific sp2-sp3 coupling of both secondary and tertiary boronic esters with electron-rich aryl lithium reagents [1-3].
Note: The transition-metal free cross-couplings of electron-deficient pyridines take place via a different mechanism than that shown below, for further information see reference 3.
 Bonet, A., Odachowski, M., Leonori, D., Essafi, S., Aggarwal, V. K., Nat. Chem., 2014, 6, 584–589 doi
 Odachowski, M., Bonet, A., Essafi, S., Conti-Ramsden, P., Harvey, J. N., Leonori, D., Aggarwal, V. K., J. Am. Chem. Soc., 2016, 138, 9521–9532 doi
 Llaveria J., Leonori D., Aggarwal, V. K., J. Am. Chem. Soc., 2015, 137, 10958–10961 doi
Expanding upon our transition-metal free cross-coupling chemistry, we have developed an efficient method for the enantiospecific conversion of boronic esters into an array of synthetically useful functional groups [1, 2].
By trapping chiral boronic esters with readily-available electron-deficient organolithium reagents, we can form chiral boronates. These boronates act as organometallic-type nucleophiles, reacting with a wide-range of electrophiles and delivering synthetically useful products through the reliable net inversion of stereochemistry [1, 2].
 Larouche-Gauthier, R., Elford, T. G., Aggarwal, V. K., J. Am. Chem. Soc., 2011, 133, 16794–16797 doi
 Sandford, C., Rasappan, R., Aggarwal, V. K., J. Am. Chem. Soc., 2015, 137, 10100–10103 doi
Our group has also successfully developed the transition-metal free stereodivergent coupling of vinyl halides with boronic esters, based upon the Zweifel olefination .
The process can be used to couple sp2 and chiral sp3 boronic esters with complete enantiospecificity, and most importantly, it allows for the highly stereoselective synthesis of either the E- or Z-alkene from a single isomer of vinyl coupling partner .
Expanding upon our Zweifel olefination methodology, we have also successfully developed a novel approach towards the enantiospecific deborylative alkynylation of enantioenriched secondary and tertiary boronic esters .
The process allows for the conversion of chiral boronic esters into terminal alkynes with high yields and excellent levels of enantiospecificity. Furthermore, internal and silyl-protected alkynes can also be produced with this process .
 Armstrong, R. J., García-Ruiz, C., Myers, E. L., Aggarwal, V. K., Angew. Chem. Int. Ed., 2017, 56, 786–790 doi
 Wang, Y., Noble, A., Myers, E. L., Aggarwal, V. K., Angew. Chem. Int. Ed., 2016, 55, 4270–4274 doi
Prostanoids are a family of biologically significant natural products derived from arachidonic acid, which are known to play crucial roles in inflammation, blood pressure control and platelet formation. Prostanoid total synthesis has been an active area of research since the 1970s and has led to the development of a number of impressive, yet lengthy, routes.
Our uniform strategy towards the total synthesis of various prostanoids and their derivatives exploits a key enal intermediate, which is prepared via a stereocontrolled organocatalytic dimerisation of succinaldehyde [1, 2].
This crystalline intermediate can be readily produced on gram-scale and serves as an advanced intermediate for the quick and efficient synthesis of a number of complex prostanoids, including PGF2α, a medicinally important natural product that was synthesised by our group on gram-scale in only 7 steps [1, 2].
 Coulthard, G., Erb, W., Aggarwal, V. K., Nature, 2012, 489, 278–281 doi
 Prévost, S., Thai, K., Schützenmeister, N., Coulthard, G., Erb, W., Aggarwal, V. K., Org. Lett., 2015, 17, 504–507 doi
Our group has a keen interest in using total synthesis to showcase the utility of our methodology in enabling facile access to a range of complex natural products.
These currently include α-Cyclopiazonic Acid, 6-Deoxyerythronolide B and the Bahamaolides A and B.
(Original text and schemes prepared by Steven Bennett. HTML coding and corrections by Oleksandr Zhurakovskyi.)