Intramolecular allylboration

Finally, several examples of intramolecular allylboration have been reported 51,92 -95. These reactions are highly stereoselective and afford only a single diastereomer in each case. 

The combination of diboration and subsequent intramolecular allylboration has been applied for the diastereose-lective synthesis of a cyclic diol (Scheme 7).65... 

In a similar fashion, allylboronates can be used as allylation reagents under hydroformylation conditions. Thus condensed 1,5-oxazadecalin systems are achieved via tandem hydroformylation/allylboration/hydroformylation sequences starting from an N-allyl-y-amidoallylboronate (Scheme 23) [77,78]. The aldehyde obtained from a regioselective hydroformylation undergoes diastereoselective intramolecular allylboration to give an intermediate al-lylic alcohol derivative. The reaction does not stop at this stage, since this... 

Hydroformylation reactions have been shown to be amenable to use in tandem or domino reaction sequences. In one elegant example, alkene 36 was subjected to rho-dium(I)-catalyzed hydroformylation, and the resulting aldehyde underwent smooth intramolecular allylboration (Scheme 5.14) [19]. This produced a new terminal alkene which underwent a second hydroformylation to provide, after workup,lactols 37 in 80% yield and with excellent diastereoselectivity. 

Intramolecular Allylboration. In one rare but impressive example involving a masked aldehyde, a domino hydroformylation/allylboration/hydroformyla-tion reaction cascade has been designed to generate bicyclic annulated... 

A masked allylic boron unit can be revealed through a transition-metal-catalyzed borylation reaction. For example, a one-pot borylation/allylation tandem process based on the borylation of various ketone-containing allylic acetates has been developed. The intramolecular allylboration step is very slow in DMSO, which is the usual solvent for these borylations of allylic acetates (see Eq. 33). The use of a non-coordinating solvent like toluene is more suitable for the overall process provided that an arsine or phosphine ligand is added to stabilize the active Pd(0) species during the borylation reaction. With cyclic ketones such as 136, the intramolecular allylation provides cis-fused bicyclic products in agreement with the involvement of the usual chairlike transition structure, 137 (Eq. 102). 

The reaction tolerated various functional groups, thus allowing the in situ preparation of allylboron compounds possessing a carbonyl group (Equation (32)).236 The tandem diboration-intramolecular allylboration provided a diastereoselective access to the cycloalkanes bearing 1,3-diols. 

Selected allyl boronates synthesized according to Equation (57) are shown in Scheme 18. The reaction provided a convenient access to allylboranes possessing a carbonyl group 168 and 169,310,311 which underwent in situ intramolecular allylboration. A variety of 5-5, 6-5, and 7-5 m-fused exomethylene cyclopentanols were synthesized... 

The intramolecular allylboration of an aldehyde function leads selectively to cir-disubstituted cyclic ethers. It has been shown that both the reactive aldehyde and the allylboronate moiety can be initially generated in situ in a masked form and then liberated simultaneously by hydrolysis of the precursor functions <1997JA7499>. This methodology was successfully applied to the one-pot synthesis of the oxocene 82, a precursor of (-l-)-laurencin (Scheme 13). A DIBAL reduction of the Weinreb amide 80, metalation with r f-butyllithium, borylation with the pinacol borate ester, and, finally, liberation of both the aldehyde and the allylboronate function by aqueous pH 7 buffer solution generated the reactive 81, which cyclized in 38% overall yield to the oxocene 82. Only the all-cis-diastereomer is formed, which means that the cyclization proceeds under high asymmetric induction from the resident stereogenic center present in 80. 

Scheme 43. Cross-coupling-intramolecular allylboration sequence...

Ahiko, T.-a., Ishiyama, T., Miyaura, N. Asequence of palladium-catalyzed borylation of allyl acetates with bis(pinacolato)diboron and intramolecular allylboration for the cyclization of oxo-2-alkenyl acetates. Chem. Lett. 1997, 811-812. 

Allylboranes add to alkynes and electron-rich alkenes to give ds addition products through a six-center transition state and allylic rearrangement [42]. Allylboration of alkynes can be followed by cyclization though intramolecular allylboration of the terminal double bond. The cyclization proceeds slowly at room temperature and rapidly at 40-100 °C(eq (29)). 

Abstract Intramolecular allylboration of a>oxo-2-alkenylboronates allows the stereoselective formation of 2-vinyl-cycloalkanols. When heteroatoms are present in the chain linking the aldehyde and allylboronate functions a variety of saturated heterocycles with a stereodefined pattern of substituents may be prepared in this manner. Rapid assembly of anellated heterocycles becomes possible by domino-hydroformylation-allylboration-hydroformylalion cascade reactions. 

Among the possible intramolecular allylmetallation reactions the intermolecular allylstannation (2) has been most widely studied by the group of Y. Yamamoto. (/) These reactions can be carried out under Lewis acid catalysis to proceed via transition states of the type 3, thermally via transition states of the type 4, and under Broensted acid catalysis, a reaction for which the nature of the transition state is not yet clear. In these reactions high to very high stereoselectivity has been attained. But there is not yet a uniform solution to reach predictable stereoselectivity in terms of attaining each of a number of possible stereoisomers selectively. It is for this reason that we wanted to evaluate the scope of the intramolecular allylboration reaction as a route to substituted tetrahydropyrans and piperidines. 

The high simple diastereoselectivity is maintained on intramolecular allylboration of either 7 or 8 to give the trans- or cis-2-vinylcyclohexanol 9 or 10. (4)... 

These results augured well for applying the intramolecular allylboration reaction to the synthesis of multisubstituted tetrahydropyrans and piperidines. 

Scheme 5 Asymmetric induction in intramolecular allylboration reactions...

The former was converted to the Z-allylboronate 28 in 32% unoptimized yield. Upon treatment of 28 with LiBp4 it was found that the intramolecular allylboration to give 29 (68%) proceeded with complete simple and induced stereoselectivity. 13)... 

Liberation of the aldehyde from 31 was followed by cyclization to give 32 as a single stereoisomer in up to 60% yield. However, the yields were compromized by partial decomposition of 31 due to the higher acid lability of the y-oxyallylboronate moiety. This induced us to develop an alternate route, in which the allylboronate moiety was generated under in situ protection of the aldehyde function. To this end, the N-methoxy-methyl amide was added to the aldehyde 33 followed by metallation with s-butyllithium. Upon addition of the mixed borate ester the intermediate 34 was formed. Hydrolysis of the reaction mixture with a pH7-buffer solution liberated both the aldehyde and the allylboronate function which immediately underwent the intramolecular allylboration reaction. This resulted in a 74% overall yield of the cyclized product 32. (14)... 

All in all, we found that intramolecular allylboration of aldehydes proceeds with predictable and reliable stereoselectivity when forming 6-membered tetrahydropyrane or piperidine rings which are adorned with adjacent vinyl and hydroxy substituents. 

Recently, allylic acetates were borylated as the first step of an efficient one-pot procedure for the allylation of aldehydes [59]. Borylation of allylic acetates can also be performed in tandem with an intramolecular allylboration (Section 6.4.1.6). 

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