A Mild Radical Procedure for the Reduction of B‐Alkylcatecholboranes to Alkanes.

Abstract

A Mild Radical Procedure for the Reduction of B-Alkylcatecholboranes to Alkanes. -A novel method for tin-free radical reduction uses methanol as the reducing agent. -(POZZI, D.; SCANLAN, E. M.; RENAUD*, P.; J. Am. Chem. Soc. 127 (2005) 41, 14204-14205; Dep. Chem. Biochem., Univ. Bern, CH-3000 Bern 9, Switz.; Eng.) -Nuesgen 09-049

Practical and Modular Construction of C(sp3)-Rich Alkyl Boron Compounds

“…Of note, the nitro group (20), iodide (21), bromide (24), silyl (25), tertiary amines (31,32), alkyne (37), olefins (38)(39)(40)(41), electron-rich heterocycles (33,42,43), and electron-deficient heterocycles (34)(35)(36) are all compatible with this transformation. Additionally, despite alcohols, acids, and amines, are known coupling partners with sulfonylhydrazones 28,29 , this transformation was competent for a range of acidic proton-containing substrates, such as phenol (22), anilines (23,28), unprotected indole (33), alkyl alcohol (26), carboxylic acid (27) and alkyl amines (29). Therefore, the relatively mild conditions and excellent chemoselectivity of this transformation enables access to products that would be either difficult or impossible to prepare via other known methodologies, including organolithium-promoted 1,2-metallate rearrangement and transition-metal catalysis (one-or twoelectron) 30 .…”

“…The synthetic applicability of this modular cross-coupling is showcased by straightforward preparation of a variety of alkyl bioisosteres-containing boronic ester building blocks (Figure 3, Panel A). Alkyl bioisosteres such as cubanes, bicyclo[1.1.1]pentanes (BCPs) and cyclopropanes, have been shown to improve drug candidates' physiochemical and pharmacokinetics properties 32 and as such, new methods for their installation and functionalization are highly sought after 33 . To this end, boronic acids derived from BCP and cubane trifluoroborate salts 34,35 , reacted smoothly with linear ketone-(100-102) and aldehyde-(103) derived sulfonylhydrazones to afford the expected coupling products in good yields.…”

“…The solvent was removed under vacuum and the crude product was purified by chromatography on silica gel to afford the product. 32,33 Compound 130…”

Synthesis of hydroxyphthioceranic acid using a traceless lithiation–borylation–protodeboronation strategy

“…Although this strategy had been applied to benzylic carbamates, the resulting benzylic boronic esters (where boron is adjacent to functionality) are very easily protodeboronated simply with TBAF·3H 2 O (TBAF, tetra-N-butylammonium fluoride), so the strategy is not generally applicable 9-12 . The major challenge in realizing this strategy is the protodeboronation of the more-stable secondary alkyl pinacol esters, remote from any functionality (for example, 3 → 4), as there were no known methods for achieving such a transformation directly, although there were methods for carrying out the overall transformation indirectly 13,14 . In this paper we describe a new protocol for protodeboronation and its tactical use in conjunction with lithiation-borylation as a new strategy for assembling molecules without trace of the functional groups used in their genesis.…”

Synthesis of Multi-Substituted Bicycloalkyl Boronates: An Intramolecular Coupling Approach to Alkyl Bioisosteres

“…The Bpin group can also be transformed to the more stable trifluoroborate salt (46), which opens further functionalization opportunities. Radical proto-deborylation 51 results in C1, C2-disubstitued BCPs (47), and C(sp 3 )-C(sp 2 ) Pd catalyzed Suzuki cross-coupling conditions 52,53 enables arylation at the bridge head (48). Lastly, cross-coupling of the in situ-generated boronic acid with sulfonylhydrazone 49 affords the Bpin 50 in 92% yield.…”