Robust synthetic methods which show broad substrate scope are of great utility in the synthesis of complex organic molecules. Within this arena, synthetic methods employing boronic esters are especially useful since they undergo a wide variety of transformations with very high levels of stereoselectivity. In particular, boronic esters can undergo single or multiple homologations using enantioenriched metal carbenoids. The addition of a suitable enantioenriched lithium or magnesium carbenoid to a boronic ester, with subsequent 1,2-migration, gives a homologated boronic ester with high stereocontrol. The process, termed lithiation-borylation, can be iterated allowing a carbon chain to be "grown" one atom at time with remarkable precision. The iterative homologation has been likened to a molecular assembly line and resembles the way nature assembles natural products, e.g. in polyketide synthase machinery. The application of lithiation-borylation chemistry to the synthesis of a broad variety of natural products is discussed in this Review.

The stereochemistry of the lipophilic side chain of (+)-rakicidin F had not been determined until recently. Using our lithiation–borylation methodology (“assembly line synthesis”) we were able to efficiently prepare the all-syn isomer as well as the C-21 epimer of the side chain, and comparison with the natural product suggested that the natural product had all-syn stereochemistry. Completion of the total synthesis using a macrolactamization of the northern amide enabled us to confirm Wang and Chen’s stereochemical findings for the structure of (+)-rakicidin F.

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