Cyclopropylboronates, synthesis

The synthesis of medicinally relevant 4-substituted 2(5//)-furanones has been achieved by a coupling reaction of the triflate derived from p-tetronic acid with alkyl-and cyclopropylboronic acids (Scheme 10.8).22 This reaction was mediated by bis(acetonitrile)dichloropalladium and silver oxide. Interestingly, optically active cyclopropyl boronic acids were not racemized during this coupling reaction. 

The methods for stereocontrolled synthesis of cyclopropylboronic esters have been studied (Scheme 29). The palladium-catalyzed reaction of diazoalkanes (method A), Simmons-Smith reaction (method B), or asymmetric Simmons-Smith reaction using chiral diamines such as 270 (method C) for chiral or achiral 1-alkenylboronic esters... 

Use as a Chiral Auxiliary Synthesis of Cyclopropylboronic Acids. The chiral dioxaborolane unit can also be used as an effective chiral auxiliary in the synthesis of enantiomerically enriched cyclopropylboronic acids. For example, 1-alkenylboronic esters bearing the tetramethyltartramide group undergo diastereoselec-tive cyclopropanations to afford the cyclopropylboronic acid (eq 11). These products can be used for in situ Suzuki coupling reactions or can be oxidized to produce 2-substituted cyclopropanols. 

Alkenylboronic acids and esters are also very useful substrates (Equation 71, Figure 1.38) [405], in particular to access substituted olefins and dienyl moieties commonly encountered in several classes of bioactive natural products [282, 406]. To this end, Kishi and co-workers examined the influence of the base, and developed an optimal variant using thallium hydroxide [281]. Recently, allylic alcohols were found to couple directly with alkyl and alkenyl boronic acids without the aid of a base [407]. In rare cases, the Suzuki reaction has been applied to the use of alkylboronic acids [296, 408], including cyclopropylboronic acids [409]. Hitherto notorious for their tendency to undergo [3-hydride elimination, alkyl bromides are now suitable as electrophiles under carefully optimized conditions that even allow Csp -Csp couplings with alkylboronic acids (Equation 72) [410]. The Suzuki reaction has also been applied very successfully in solid-phase chemistry and combinatorial library synthesis [411]. It has been applied industrially [412], especially in medicinal chemistry, e.g. in the production of the antihypertensive drug losartan [195]. 

Scheme9.16 Asymmetric synthesis of cyclopropylboronates using a chiral director on the boron atom.

---