Lithiation–borylation methodology in the total synthesis of natural products

Abstract

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.

A noble-metal-free metal-organic framework for alkane borylation

“…Borylation of C(sp 3 )-H bond produces value-added alkyl boronates that can be further converted to other functional groups 4,[7][8][9][10][11] , but requires catalysts based on noble metals such as Ir [12][13][14][15][16][17][18] and Ru [19][20][21][22][23][24] and tailor-made ligands [25][26][27][28] . Noble-metal-free alkane borylation has only been achieved recently by photochemistry 29,30 .…”

“…Secondary C(sp 3 )-H or C(sp 2 )-H did not undergo borylation reaction as shown by the lack of the expected products from substrates 2-11. Zr-BTC-H has a good substrate scope with high catalytic activity for gaseous alkanes (1-3), long chain alkanes (4-5), aryl alkanes (6-7), methyl cycloalkanes (8)(9), and ethers (10)(11). Zr-BTC-H selectively borylate the primary C(sp 3 )-H bonds in 3-11.…”

Stereocontrolled Total Synthesis of Bastimolide B Using Iterative Homologation of Boronic Esters

“…Their complex structures coupled with their significant biological activity have fueled intense interest in their synthesis . Indeed, the stereoselective synthesis of polypropionates/polyacetates represents one of the crowning achievements of synthesis in the 20th century. − Despite the advances in polyketide synthesis, several challenges still remain, such as the stereoselective construction of 1,5-stereogenic centers . Of particular interest is the construction of 1,5-polyols, as they occur in many polyketides .…”

Copper-Catalyzed Protoboration of 1,3-Diynes as a Platform for Iterative Functionalization

“…Recently, organoboron compounds have shown great promise in the automated synthesis of small molecules with high complexity. Some of the remarkable pioneering contributions from the Suginome, − Aggarwal, − Burke, − Crudden, and Tsuchimoto groups have led to the practical application of iterative coupling in the total synthesis of complex natural products and pharmaceuticals. Suginome and other groups − ,, demonstrated the iterative coupling capabilities of -Bdan (dan: 1,8-diaminonaphthalene) building blocks employing the Suzuki-Miyaura Coupling (SMC) reaction.…”

“…Suginome and other groups − ,, demonstrated the iterative coupling capabilities of -Bdan (dan: 1,8-diaminonaphthalene) building blocks employing the Suzuki-Miyaura Coupling (SMC) reaction. Burke and co-workers pioneered the automated synthesis of several natural products using -B­(MIDA) ester (MIDA: N -methyliminodiacetic acid) building blocks under SMC conditions. − The Aggarwal group developed a unique transition metal-free iterative coupling strategy using the lithiation-borylation sequence in a stereocontrolled manner. − …”